Pharmaceutical Dosage Forms and Drug Delivery Systems

DRUG- any article or agent that is used for diagnosis, mitigation, treatment, prevention and cure of
diseases in man and in animals.
Diagnosis- to determine the disease
Mitigation-alleviate.. lessen.. ease
Treatment- to make someone healthy again
Prevention – to stop
Cure –relieve of symptoms

DOSAGE FORMS
 preparations designed to contain a specified quantity of medication for ease and accuracy of dosage
administration
 are drug products containing
o Active Pharmaceutical Ingredients (API)/Drug- the one that exerts therapeutic effects
o Non-Active Ingredients/Excipients/Additives/Adjuncts- non drug substances which are usually
inert

Part I. GENERAL CONSIDERATIONS IN DOSAGE FORM DESIGN

1. PHYSICAL AND CHEMICAL PROPERTIES OF DRUG SUBSTANCES

a) PHYSICAL DESCRIPTION – solid, liquid, or gaseous
the purity of the chemical substance is essential for its identification and for evaluation of its chemical,
physical and biological properties
chemical property ( structure, form, and reactivity)
physical property ( physical description, particle size, crystalline structure, melting point and solubility)
biological property- ability to get to a site of action and elicit response

b) PARTICLE SIZE- dissolution rate, bioavailability, content uniformity, taste, texture, color and stability;
flow properties and sedimentation rates
DISSOLUTION- Rate limiting step in the absorption process affects onset, intensity and duration of
response and control the overall bioavailability of the drug from the dosage form
BIOAVAILABILITY- the proportion of a drug or other substance which enters the circulation when
introduced into the body and so is able to have an active effect.
CONTENT UNIFORMITY- equivalent amount of active pharmaceutical ingredient or drug substance
when assaying is present when for qualitatively assessing or quantitatively test is done
FLOW PROPERTIES- FREE FLOWING or Cohesive (sticky) type
SEDIMENTATION RATE- time of separation of powder from the liquid
POLYMERIZATION-crystal or amorphous
SOLUBILITY- Should possess aqueous solubility for therapeutic effect

c) PARTITION COEFFICIENT AND DISSOCIATION CONSTANT-

PARTITION COEFFICIENT-Measure Of Drug’s Lipophilic Property
DISSOCIATION CONSTANT- The Extent Of Ionization Of A Drug Has A Strong Effect On Its Extent Of
Absorption, Distribution And Elimination

d) POLYMORPHISM- Affects melting point and solubility

e) SOLUBILITY- Affected by particle size and pH

STABILITY- Is defined as the extent to which a product retains, within specified limits, and throughout its
period of storage and use, the same properties and characteristics that it possessed at the time of its
manufacture

Five types of Stability

 Chemical
o Each active ingredient retain its chemical integrity and labeled potency, within specified limits.
 Select proper storage conditions
 Select proper container
 Anticipating drug interaction when mixing
 Physical
o The original physical properties, including appearance, palatability, uniformity, dissolution and
suspendability are retained
 Microbiological
o Sterility or resistance to microbial growth is retained. Antimicrobial agents that are present
o retain effective within specified limits
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  Therapeutic
o The therapeutic effect remain unchanged
 Toxicological
o No significant increase in toxicity occur

Mechanism of degradation
HYDROLYSIS- A solvolysis process in which drug interact with water to yield breakdown products of different
chemical constitution (replace water with other solvents example: liquid- Glycerin, propylene glycol, and
alcohol ; for parenteral- vegetable oils ; use of buffering agent; refrigeration; for reconstitution-expiry date
change 1 week room temperature 2 weeks if refrigerated)

OXIDATION-Involves the loss of electrons from an atom or a molecule (antioxidant)

◦ Common to aldehydes, alcohols, phenols, sugars, alkaloids, and unsaturated fats and oils
Aqueous- Sodium sulfite, sodium bisulfite, sodium metabisulfite, hypophosphorous acid, ascorbic acid
Olagenous- Alpha-tocpoherol, butyl hydroxyanisol, ascorbyl palmitate

POLYMERIZATION-Involves a reaction between two or more identical molecules with a resultant formation of
a new and generally larger molecule

DECARBOXYLATION- Decomposition of an organic acid and the consequent release of carbon dioxide

DEAMINATION-Involves the removal of the nitrogen-containing group from an organic amine

2. PRESERVATION AGAINST MICROBIAL CONTAMINATION

PRODUCTS REQUIRING PRESERVATIVES
 Syrups, Emulsions, Semisolid preparations, Ophthalmic products, and Parenterals (multiple-dose
package)
PRODUCTS NOT REQUIRING PRESERVATIVES
* Alcoholic and hydroalcoholic solutions (15-20% alcohol), Elixirs, tinctures and spirits are self-
preserving and Large Volume Parenterals
◦ Under 6 years of age – 0.5 %
◦ 6-12 years old – 5 %
◦ Over 12 years old – 10 %

Considerations in preservation of Sterile products

 Parenterals and Ophthalmic preparations are sterilized by AUTOCLAVING, BACTERIAL
FILTRATION AND DRY HEAT, however may still require additional preservatives
 Chlorobutanol, Benzalkonium Chloride and Phenyl Mercuric Nitrate are the frequently used
preservatives in ophthalmic preparations because of their low degree of irritant qualities
 Acidic preservatives are more effective in acid media,
 Alkaline preservatives are less effective in acid or neutral media but more effective in alkaline media
 Examples are benzoic acid and sodium benzoate, alcohol, cresol and phenol, chlorobutanol,
benzalkonium chloride and phenyl mercuric acetate and the parabens (methyl- and propylparaben) –
antifungal

3. APPEARANCE AND PALATABILITY FLAVORING OF PHARMACEUTICALS

FLAVORANT
 Cinnamon, raspberry and orange flavors – mask SALTY taste of drugs (Chlorides of Na, K, and
Ammonium)
 Cocoa – mask the BITTER taste of drugs (Alkaloids, Epsom salt)
 Fruit or citrus flavors- combat acid or SOUR taste of drugs
 Organic esters, alcohols, and aldehydes are pleasant to taste
SWEETENING AGENTS
 SUCROSE – Commonly used sweetener; from sugar cane/sugar beet
 GLYCERIN – less sweet than sucrose
 SACCHARIN – 300 times as sweet as sucrose; has a bitter after taste
 ASPARTAME – 180 to 200 times sweeter than sucrose; contraindicated to phenylketonurics
 CYCLAMATE – has carcinogenic potential
 ACESULFAME POTASSIUM – 130 times as sweet as sucrose
 STEVIA POWDER – natural, non-toxic, safe and about 30 times sweeter than sucrose.
COLORING PHARMACEUTICALS
 LIQUID DYES – the amount added to liquid preparations ranges from 0.0005 to 0.001%
depending upon the colorant and the depth of color desired.
 LAKE PIGMENTS - suitable for coloring products in which the moisture levels are low
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 * FD and C lake is a pigment consisting of a substratum of alumina hydrate on which the dye is
absorbed or precipitated.
CLASSIFICATION OF CERTIFIED COLOR ADDITIVES
1. FD & C – used in food, drugs, and cosmetics
2. D & C – approved for use in drugs, some in cosmetics, and some in medical devices.
3. External D & C – the use of which is restricted to external parts of the body, not including the lips
or any body surface covered by mucous membrane
 DRUG PRODUCTS REQUIRING COLORANTS
capsules, compressed tablets, sugar-coated tablets and suspensions
 DRUG PRODUCTS THAT DO NOT CONTAIN COLOR ADDITIVES
ophthalmic products, parenteral products, ointments, and suppositories

SAFETY CONCERNS OF SOME COLOR ADDITIVES

1. FD & C Yellow No. 5 (tartrazine)- can cause allergic reactions to patient allergy with ASPIRIN; FDA
requires the listing of this dye on the labels of food and ingested drugs containing the substance
2. FD & C Red No. 4 – now permitted only in externally applied drugs and cosmetics because of
unresolved safety questions.
3. FD & C Red No. 2 (amaranth) – certification has been withdrawn since it can cause cancer in rats

4. PACKAGING, LABELING AND STORAGE OF PHARMACEUTICALS

CONTAINERS
According to USP, it holds the article and is or maybe in direct contact with the article immediate container (the
one that is in direct contact with the article at all times) closure

According to their ability to protect the content from external conditions

 Well closed container – protects content from extraneous solids and from loss of the drug under
ordinary conditions of handling, shipment, storage and distribution
 Tight closed container – protects the contents from contamination by extraneous solids, liquids, or
vapors, from the loss of the drug and from efflorescence, deliquescence, or evaporation under the
usual conditions of handling, shipment, storage and distribution
o hygroscopic substance- absorbs moisture from air but do not change its form
o deliquesent - absorbs moisture from air and it will liquify
o efflorescent-efflorescent substances are those substances which when exposed to atmosphere
loose moisture partially or completely and changes into an amorphous powder
 Hermetic container – impervious to air or any other gas under the ordinary condition of handling,
shipment, storage and distribution
 Light-resistant container – protects the contents against photochemical degradation. Ex. Amber-
colored bottle
 Child-resistant container – are designed to prevent the child accessing the potentially hazardous
product.
 Tamper-resistant container – closed container fitted with a device that irreversibly indicates if the
container has been opened. Ex. Strip packs, blister packs, tape seals, bubble packs, Shrink seal or
band, Foil, paper or plastic pouch, Bottle seal (inner cap), Tape seal, Breakable cap, Sealed Tube,
Sealed carton, Aerosol container

According to content
 Single-dose container – holds the product which is intended for single use. Ex. Glass ampule,
prefilled syringes and cartridges
 Multiple-dose container – permits withdrawal of successive portions of the contents without changing
the strength or endangering the quality of the remaining portions. Ex. Vials and plastic tablet bottles

Plastic Containers
 Plastic materials used are polyvinyl chloride (PVC), polyethylene terephthalate (PET),
amorphous polyethylene terephthalate glycol (APET), and polyethylene terephthalate glycol
(PETG)
◦ polyvinyl chloride (PVC) – rigid and has good clarity; useful in blister packaging of tablets and
capsules
o -not suitable when gamma sterilization is required
◦ polyethylene terephthalate (PET)
◦ amorphous polyethylene terephthalate glycol (APET)
◦ polyethylene terephthalate glycol (PETG)
◦ APET and PETG have excellent transparency and luster can be sterilized with gamma radiation

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  Problems encountered in the use of plastics in packaging are;
 PERMEABILITY of the containers to atmospheric oxygen and to moisture vapor
 LEACHING of the constituents of the container to the internal contents
 SORPTION of drugs from the contents to the container
 TRANSMISSION of light through the container
 ALTERATION of the container upon storage

Glass Containers
Categories of glass containers
TYPE GENERAL DESCRIPTION USES

I highly-resistant borosilicate glass Parenteral

products
Most resistant
II treated soda-lime glass Parenteral
products
III soda lime glass Parenteral
products
NP general purpose soda-lime glass Other preparations

LABELING
◼ Label on immediate container
◼ Package inserts
◼ Company literature
◼ Advertising and promotional materials (brochures, booklets, mailing pieces, file cards, bulletins,
price list, catalogs, sound recording, film strips, motion picture films, slides, exhibits, displays.
Etc…

Prescription drug label

 With Rx symbol, or the Legend: ……… Act prohibits dispensing without prescription
 For Controlled substances – The statement: “Warning – May be habit forming”
OTC LABEL
 Statement of pharmacologic category; No Rx symbol
STORAGE CONDITION
 COLD – any temperature not exceeding 8C(46F)
o REFRIGERATOR – a cold place in which the temperature is maintained thermostatically
between 2 and 8C (36 and 46F)
o FREEZER – a cold place in which the temperature is maintained thermostatically between -20
and -10C (-4 and 14F)
 COOL – Any temperature between 8 and 15C (46 and 59F)
 ROOM TEMPERATURE – the temperature prevailing in the working area.
 CONTROLLED ROOM TEMPERATURE – usual working environment of 20C and 25C(68F to 77F)
but also allows temperature variations between 15C and 30C(59F and 86F).
 WARM – Any temperature between 30 and 40C (86 and 104F).
 EXCESSIVE HEAT – Any temperature above 40C (104F)
 PROTECTION FROM FREEZING
o Risks of freezing: breakage of container; loss of potency/strength; destructive alteration of the
dosage form.

POWDERS AND GRANULES

POWDER A dosage form composed of a solid or mixture of solids reduced to a finely divided state and
intended for internal (oral powder) or external (topical powder) use
Latin name Pulvis

Advantages
 Flexibility in compounding
 Good chemical stability
 Rapid dispersion of ingredient because of small particle size

DISADVANTAGES
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  Time consuming to prepare
 Inaccuracy of doses
 Difficulty in administration
 Not suitable for dispensing

Particle size
Descriptive Powder Characteristic
Term Number
Very coarse No. 8 All particles pass through a # 20 sieve and NMT 20% through a # 60 sieve

Coarse No. 20 All particles pass through a # 20 sieve and NMT 40% through a # 60 sieve
Moderately No. 40 All particles pass through a # 40 sieve and NMT 40% through a # 80 sieve
coarse
Fine No. 60 All particles pass through a # 60 sieve and NMT 40% through a # 100 sieve
Very fine No. 80 All particles pass through a # 80 sieve. There is no limit to greater
fineness.

PREPARATION OF POWDERS
1. COMMINUTION –process of reducing particle size
Small Scale
 Trituration
o Continuous rubbing or grinding of powder to reduce its particle size
o Mortar and pestle (small scale)
o Mills and pulverizers (large scale)

 Levigation
o process of decreasing the particle size of powders via triturating them with a mortar and
pestle/ ointment tile(pill tile/Ointment slab) along with a small amount of liquid wherein the
substance is insoluble to.
o This specific liquid is called a levigating agent (mineral oil or glycerin) and is viscous in
nature with a low surface tension to easily wet the solid particles
o act as a lubricant as they also allow a smoother incorporation of solids in the preparation.
 Pulverization by intervention
o applied to substances which are gummy or resist grinding.
o The substance are reduced using an additional material that can be removed easily after
pulverization is complete
o Interventing solvent in which that material is soluble(volatile solvent such as alcohol or
acetone); easily removed after pulverization
o The dissolved powder is then mixed in a mortar or spread on an ointment slab to enhance
the evaporation of the solvent. As the solvent evaporates, the powder will recrystallize out of
solution as fine particles
o Mortar and pestle
o Ex. Camphor + alcohol iodine crystals+ ether

2. MIXING / BLENDING OF POWDERS

NON-POTENT DRUGS
 Spatulation
 useful for solid substances that liquefy or form eutectic mixtures (i.e., mixtures that melt at a
lower temperature than any of their ingredients) when in close, prolonged contact with one
another because little compression or compaction results.
 For eutectic [mixture of substances that liquefy when mixed, rubbed or triturated together]
The melting points of many eutectic mixtures are below room temp.
 mixtures (phenol, camphor, menthol, thymol, aspirin, phenyl salicylate)
 Pill tile
 Trituration
o Glass – smooth, non porous; good for simple mixing; can be used for solutions/suspensions
o Wedgewood – crystals
o Porcelain or ceramic – soft, aggregate crystals; for semi-solid
 Sifting
o Powders are mixed by passing them through sifters similar to those used to sift flour.
o not acceptable for the incorporation of potent drugs into a diluent powder
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  Tumbling
o is the process of mixing powders in a large container rotated by a motorized process.
o These blenders are widely used in industry, as are large-volume powder mixers that use
motorized blades to blend the powder in a large mixing vessel.
POTENT DRUGS
 Geometric Dilution
o Applicable to small amounts of potent substances to be mixed with a large amount of
diluent.
o ensures uniform distribution of the potent substance.

3. PACKAGING OF POWDERS
 BULK POWDERS – large quantities; wide-mouthed glass, perforated, or sifter can, or in aerosol
container
o ORAL POWDERS – antacid or laxative powders, taken by mixing with water
o DOUCHE POWDERS – dissolved in warm water for vaginal use
o DUSTING POWDERS – medicated or non-medicated powders for external application to the skin;
locally applied non toxic
o DENTRIFICES – is a substance used with a toothbrush for the purpose of cleaning the accessible
surface of the teeth. generally containing a soap or detergent, mild abrasive, and anti-cariogenic
agent (tending to prevent tooth decay)
o INSUFFLATION- finely divided powders that are intended to be applied in a body cavity, such as
the ears, nose, vagina, tooth socket, or throat. With the use of bulb applicator (insufflator)

 DIVIDED POWDERS- dispensed in the form of individual doses and generally dispensed in papers,
properly folded
o Latin name Chartulae
o Methods of dividing powders individual weighing and block and divide method
o Types of paper
o Bond paper- has no moisture properties
o Vegetable Parchment is a thin, semi opaque, moisture resistance paper
o Glassine paper- is a glazed, transparent moisture resistance paper; no protection for
photodegradation; can be used for volatile substances
o Wax Paper is a transparent waterproof paper for hygroscopic, deliquescent and volatile drugs
o Hygroscopic powders will absorb moisture from the air
o Deliquescent powders will absorb moisture from the air to the extent that they will
partially or wholly liquefy
o Efflorescent powder when exposed to air, loses this water through evaporation; gives off
water of crystallization

Problems Encountered in the Preparation of Powders

Volatile substances can be last by volatilization after they are incorporated with powders.
• use of heat sealed plastic bags or double wrapping with waxed or glassine paper inside of a white bond
paper
Liquids are incorporated into divided powders in small amounts
• Magnesium carbonate, starch or lactose can be added to increase absorbability of the powders by
increasing the surface area
Hygroscopic and deliquescent substance that became moist because of an affinity for moisture in the air
• can be prepared as divided powders by adding inert diluents
• Double wrapping is desirable

Types of Powder
Topical Powders
• Consist of a base or vehicle, such as cornstarch or talc; an adherent, such as magnesium stearate,
calcium stearate, or zinc stearate; and possibly an active ingredient, along with an aromatic material.
• Must be impalpable(the powder is unable to be felt by touch because the powder is very fine) and free
flowing
• Easily adhere to the skin
• Passed through at least a No. 100-mesh sieve to minimize skin irritation

Medicated Powders
INTERNAL USE
• Oral administration after mixing with water
• Inhalation (local or systemic)
• Powder for reconstitution
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 • Oral, injection and vaginal douche
EXTERNAL USE
• Dusted from a sifter-type container or powder aerosol
• Label: EXTERNAL USE ONLY

Aerosol Powders
• Oral inhalation
• Makes use of dry powder inhaler / metered dose inhaler
• Delivers micronized particles of medication in metered quantities
• Powder size: 1 to 6 𝜇m in diameter
• tx of asthma and other bronchial disorders that require distribution of medication deep in the lungs

GRANULES
• composed of dry aggregates of powder particles
• may be swallowed as such, dispersed in food, or dissolved in water.
• compacted into tablets or filled into capsules
• Size: usually 4 to 12-sieve size range
• Sieve size for tablet formulation: No. 12-20
• Characteristics
• Free-flowing, thus are used in tablet making
• More stable to the effects of atmospheric humidity
• Less likely to cake or harden upon standing
• More easily wetted

Methods of granulation
1. Dry Granulation Method
• Dry fusion method
• For drugs that are moisture sensitive or heat liable
• The water of crystallization from Citric acids serves as a binding agent
• Heating cause the release of water of crystallization from the citric acid
mix-dry-sieve-dry
2. Wet Granulation Method
• Wet fusion method
• involves the addition of small amounts of liquid (water. ethanol, isopropyl alcohol) acts as
binding agent
• moisten powder-form solid mass- screen- dry the granules

Effervescent Granulated Salts

 Are granules or coarse to very coarse powders containing a soluble medicinal agent in a dry mixture
usually composed of sodium bicarbonate(alkalinizer), citric acid (acidifier), and tartaric acid
(acidifier).Ratio: 1 citric:2tartaric
 When mixed with water, acids and base react to liberate carbon dioxide resulting in effervescence.
 Tartaric acid alone is used as the sole acid, the resulting granules readily lose their firmness and
crumble.
 Citric acid alone results in a sticky mixture difficult to granulate

CAPSULES
 solid dosage forms in which the medicinal agents and/or inert substances are enclosed in a small
gelatin shell
 EMPTY CAPSULE SHELLS
o Made of gelatin, sugar and water
o Gelatin - partial hydrolysis of collagen obtained from the skin, white connective tissue, and
bones of animals.
o Gelatin is stable in air when dry, if moist-microbial decomposition
o Gelatin contain 13% to 16% of moisture
o Types of gelatin:
 Type A Gelatin – derived from pork skin by acid processing
 Type B Gelatin – obtained from bones and animal skins by alkaline processing
 Vegetable capsule shells are prepared with Hydroxypropylmethylcellulose
PREPARATION OF EMPTY CAPSULE SHELLS
1. Preparation of gelatin mixture
2. Dipping of pins into a melted gelatin mixture
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3. The plate and the pegs are slowly lifted from the bath
4. The gelatin is dried by a gentle flow of temperature- and humidity-controlled air.
5. The capsule is trimmed mechanically to the proper length
6. Removed from the pegs
7. The capsule bodies and caps are joined together.

 TYPES OF CAPSULES
1. HARD GELATIN CAPSULES
 Hard gelatin capsule consist of Two pieces of cylinders closed at one end.
 The shorter piece is called the cap. This cap fits over the open end of longer piece called body
 Dry filled capsule or 2 piece capsule
 Used by community pharmacist in extemporaneous compounding of prescriptions
 Commonly employed in clinical drug trials to compare investigational drug to another drug or a
placebo
 Capsule shell sizes are 000, 00,1,2,3,4,and 5
 Components gelatin, water, sugar , colorant, opaquant (titanium dioxide), 0.15% sulfur dioxide to
prevent decomposition
 Moisture content: 13-16% (below 10% brittle and crumble above 16% sift, distorted and lose their
rigid shape)
 Fill: powder or granulate; pellet mixture; paste; capsule; tablet

PREPARATION OF FILLED HARD GELATIN CAPSULE

 Developing and preparing the formulation and selecting the size of capsule
CAPSULE FORMULATION
 Active ingredient
 Diluents or Fillers – produce the proper capsule fill volume (ex. lactose, microcrystalline
cellulose and starch)
 Disintegrants – assist break-up and distribution of the capsule contents in the stomach (ex:
pregelatinized starch, croscarmellose, sodium starch glycolate)
 Lubricants or glidants – improve flow properties of powder mixture (ex: Fumed silicon
dioxide, magnesium stearate, calcium stearate, stearic acid or talc)
 Surface active agents – facilitates wetting of powder by the GI fluids (ex: Sodium lauryl
sulfate)
SELECT CAPSULE SIZE
 amount of fill materials
 assessing the density or fluffiness of the powder
 Filling the capsule shells
 “Punch” method may be used in small scale
o Non-potent drugs- FIRST filled capsule should be weighed other capsule..
Periodically
o POTENT- each capsule should be weighed
 Capsule filling machine
o Hand operated capsule filling machine / Manual capsule Filling machine
o Automatic filling machine
 Capsule sealing (optional)
 Extemporaneously, by lightly coating the inner surface of the cap with a warm gelatin
solution
 Large scale- heat welding; liquid welding- Sealing of capsules is achieved by heating at 37-
40°C

 Cleaning and polishing the filled capsule

 Small scale- cleaning with a clean gauze or cloth
 Large scale- vaccum

2. SOFT GELATIN CAPSULE

 One piece
 Also known as “soft-elastic capsule”
 Soft, globular, gelatin shell thicker than HGC
 Components:
o gelatin 35-45%,
o water 40%,
o plasticizer 15-25% (glycerin or polyhydric alcohol such as sorbitol) to render it elastic or
plastic like Ratio of drug and plasticizer 1:0.08

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 o preservatives (paraben) to prevent fungal growth
o Colorant -Dye/Pigment (as needed) single or two toned color
o Opacifier- (as needed)
o Other (flavour, sugar) as needed
 Moisture Content 6-10%
 Hermetically seal and encapsulate liquids, suspensions, pasty materials or dry powders
 Prepared by plate process ; rotary die process; reciprocating die process
PLATE PROCESS
• oldest commercial process that uses set of molds to form capsules
• This method is used for small scale preparation of soft gelatin capsules and capsules
formed generally, had one flat side.
• Warmed sheet of plain or coloured plasticized gelatin is placed over a die plate having a
number of depression or molds or numerous die pockets.
• The capsule wells are then filled with medication-containing liquid.
• A second sheet of gelatin is carefully placed on top of the filled wells followed by the top
plate of the mold.
• This equipment is no longer available.
ROTARY DIE PROCESS
• two plasticized gelatin ribbons are continuously and simultaneously fed with liquid or
paste fill between the rollers of the rotary die mechanism
RECIPROCATING DIE PROCESS
• The gelatin ribbons are fed between a set of vertical dies that continually open and close
to form rows of packets in gelatin ribbons

Packaging
• Tight, well-closed, and light-resistant container (depending on the item)
• Strip pack
• Blister pack
• Capsule should be store in cool and low humidity
Storage
• high humidity and additional moisture is absorbed- distorted and lose their rigid shape.
• extreme dryness, moisture present in the gelatin capsules is lost- brittle and crumble
• Desiccant materials is added to protect moisture (dried silica gel, clay , activated charcoal)

TABLETS
 Are solid pharmaceutical dosage forms containing drug substances usually prepared with the aid of
suitable excipients
 Solid dosage forms that are prepared by molding (soft tablet) or compression method (Hard tablet)
o Compression method: wet granulation method, dry granulation method, or by direct
compression
TABLET EXCIPIENTS
 DILUENTS – fillers designed to make up the desired bulk, flow properties and compression
characteristics (examples: lactose, mannitol, starch, dibasic calcium phosphate, sorbitol, powdered
cellulose)
 BINDERS – used to cause adhesion of powder particles in tablet granulations (Ex.: Acacia, CMC,
gelatin, MC, EthC, compressible sugar, liquid glucose)
 DISINTEGRANTS – promote disruption of solid mass into smaller particles (Ex.: CMC, CMC Calcium,
Microcrystalline cellulose, starches)
 GLIDANTS – enhance flow properties of powders (Ex.: Colloidal silica, Cornstarch, talc)
 LUBRICANTS – reduce friction during tablet compression (Ex.: Ca/Mg/Zn stearate, Mineral oil, stearic
acid)
 COLORS AND DYES
 FLAVORING/SWEETENING AGENTS – usually limited to chewable and buccal tablets
 TABLET COATING AGENTS
o Sugar-coating agents – liquid glucose, sucrose
o Film-coating agents – MC, EthC, Hydroxy-ethyl/propyl cellulose
o Enteric-coating agents – cellulose acetate phthalate, shellac (35% in alcohol, “pharmaceutical
glaze”)

TABLET TYPES AND CLASSES

1. TABLETS FOR ORAL INGESTION
 Compressed tablets- 1 layer; Uncoated tablet
o With sufficient pressure forcing the powders or granules to make the desired shape

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 o Contained no special coating
 Multiple-compressed tablets – 2 or more layer, compression coated, or dry-coated
 Prepared by subjecting the fill material to more than a single compression
 Each layer may contain different medicinal agent, separated for reasons of:
o chemical or physical incompatibility
o staged drug release
o simply for the unique appearance of the layered tablet
 Sugar-coated tablets – The sugarcoat protects the enclosed drug from the environment and provides a
barrier to objectionable taste or odor
Disadvantage
o 50% larger and heavier than the original uncoated tablet
o Time consuming since it requires 5-6 stages
 Film-coated tablets- Coated with a thin layer of polymer capable of forming a skin-like film over the
tablet
Advantages of film-coating over sugarcoating include;
o more durable
o less bulky
o less time-consuming to apply
 Gelatin-coated tablets (GELCAPS)- Capsule shaped compressed tablet (GELCAP)
facilitates swallowing; More tamper-evident than unsealed capsules
 Enteric-Coated Tablets – has a delayed release feature; tablet is intact in the stomach but disintegrate
in small intestine

2. TABLETS USED IN THE ORAL CAVITY (drugs destroyed by gastric juices and poorly absorbed in GIT)
 Buccal- to be dissolved on buccal pouch. They are designated to erode slowly (4hrs disintegration time)
 Sublingual- under the tongue- dissolve rapidly and provide drug effect
 Lozenges or Troches - are disc-shaped, solid dosage forms containing medicinal agent and generally a
flavoring substance in a hard candy or sugar base.
o They are intended to be dissolved slowly in the oral cavity for localized effects
o Made by compression or molding
 Rapidly Dissolving Tablets- Disintegrating or dissolving in the mouth within 1 minute, some within 10
seconds. Liquefy in tongue
 Chewable tablets – disintegrate smoothly
o It disintegrate smoothly and rapidly when chewed or allowed to dissolve in the mouth.
o Are especially useful for administration of large tablets to children and adults who have difficulty
swallowing solid dosage forms
o Generally, do not contain disintegrant
o Mannitol is the common excipient
 Accounts for 50% or more of the weight of many chewable tablets
 Other sweeteners, such as sorbitol, lactose, dextrose, crystalline maltose, and glucose
may be substituted for part or all of the mannitol
 Xylitol may be used for sugar-free chewable tablets

3. TABLETS USED TO PREPARE SOLUTION

 Effervescent tablets- prepared by compressing granular effervescent salt ; releases carbon dioxide with
in contact with water
 Tablet triturates- also known as molded tablets
o are small, usually cylindrical molded or compressed tablet containing small amount of usually
potent drugs
o Molded tablets are generally prepared by mixing the active drug with lactose, dextrose,
sucrose, mannitol, or some other appropriate diluent that can serve as the base.
o Lactose is the preferred base but mannitol adds a pleasant, cooling sensation and additional
sweetness in the mouth.

4. OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION

PILLS
 Are small, round, solid dosage forms containing a medicinal agent intended to be administered orally.
 Classes of pills according to weight
o Parvules (small pills) – 20 mg
o Granules – 20 to 60 mg
o Pills – 60 to 500 mg
o Boluses (big pills) – 700 to 2000 mg; for veterinary use
LOLLIPOPS
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  raspberry sugar-based lozenge on a stick containing fentanyl citrate
 Actiq is the first product designed to aid in controlling breakthrough pain in cancer patients
 Immediate relief its effect last for 15 minutes

Packaging
• Stored in tight containers, in places with low humidity and protected from extremes in temperature
• Packaged with a desiccant packet
• Drugs affected by light are packaged in a light-resistant containers

MODIFIED RELEASE DOSAGE

Modified release
 Used to describe dosage forms having drug-release features based on time, course, and/or location
that are designed to accomplish therapeutic or convenience objectives not offered by conventional or
immediate-release forms
 These includes the extended and delayed release, repeat action and targeted release
Extended release (ER)
 One that allows a reduction in dosing frequency from that necessitated by a conventional dosage form
 means the pill is formulated so that the drug is released slowly over time
Repeat-action tablets
 Prepared for initial dose of drug is released immediately second dose follows later
 Immediate release – tablet’s outer shell or coating
 Second release – tablet’s inner core separated by a slowly permeable barrier coating
 Drug from the inner core is exposed to body fluids and released 4 to 6 hours after
administration
 Best suited for treatment of chronic conditions requiring repeated dosing
 Drug candidates for repeat action:
 Those with low dosage and fairly rapid rates of absorption and excretion
Delayed-release
 A delayed-release dosage form is designed to release the drug at a time other than promptly after
administration.
 Reasons for delayed-release formulations
 may be to protect a drug destroyed by gastric fluids,
 to reduce gastric distress caused by drugs particularly irritating to the stomach, or
 to facilitate gastrointestinal transit for drugs that are better absorbed from the intestines
 Coated tablets and capsules that remain intact in the stomach to release their contents in the intestine
are called enteric coated.
 Enteric coating may be:
 pH dependent- coating breaks down in the less acidic environment of the intestine
 time dependent-coating erodes by moisture over time during GI transit
 enzyme dependent- deteriorating as a result of the hydrolysis-catalyzing action of
intestinal enzymes
 Material for enteric coating
 Fats, fatty acids, waxes, shellac, and cellulose acetate phthalate
Targeted release
 Targeted release describes drug release directed toward isolating or concentrating a drug in a body
region, tissue, or site for absorption or for drug action.

Characteristics of drugs that make them candidates for development into an extended-release product
 They exhibit neither very slow nor very fast rates of absorption and excretion
 They are uniformly absorbed from the gastrointestinal tract.
 They are administered in relatively small doses.
 They possess a good margin of safety.
 They are used in the treatment of chronic rather than acute conditions.

Technologies used in extended-release dosage forms:

1. COATED BEADS, GRANULES, AND MICROSPHERES
 The drug is distributed into beads, pellets, granules or other particulate system
 The beads, granules, or microspheres are coated in various thickness by:
 Lipid material
 Beeswax, carnauba wax, glyceryl monostearate, or cetyl alcohol or cellulosic material
like ethylcellulose
 Cellulosic material
 Ethylcellulose
 Commercial aqueous coating systems
 Ethylcellulose with plasticizer
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  Coated beads, granules, or microspheres may be placed in capsules or compressed in tablets
2. MICROENCAPSULATION
 Solids, liquids, or even gases may be encapsulated into microscopic size particles through the
formation of thin coatings of “wall” materials around the substance being encapsulated.
 wall-forming materials
o Gelatin, polyvinyl alcohol, ethylcellulose, polyvinyl chloride
3. MATRIX TABLETS
 Embedding drug in an inert plastic matrix such as polyethylene, polyvinyl acetate, or polymethacrylate
 Drug is slowly released from the plastic matrix by diffusion
 The inert tablet matrix, expended of drug, is excreted with the feces
4. OSMOTIC SYSTEMS
 OROS SYTEM – pioneer oral osmotic pump delivery system
1. Composed of a core tablet surrounded by a semi-permeable membrane coating having a 0.4-mm-
diameter “hole” produced by a laser beam
2. Core tablet consists of:
1. “ACTIVE” layer – containing the drug
2. “PUSH” layer – containing the polymeric osmotic agent
Other osmotic system
 GITS (Gastrointestinal Therapeutic System) – A type of push-pull osmotic system
 COER (Controller-Onset Extended Release) - Drug is released 4 to 5 hours after tablet ingestion.
The delay in drug release is effected by a slowly solubilized coated layer between the active drug core
and the outer semipermeable membrane
5. ION-EXCHANGE RESINS
 A solution of a cationic drug may be passed through a column containing an ion-exchange
resin, forming a complex by the replacement of hydrogen atoms.
 A complex of resin-drug is formed; tableted, encapsulated or suspended in an aqueous vehicle
 The release of the drug is dependent upon the pH and the electrolyte concentration in the GIT
6. COMPLEX FORMATION
 Drug substances are combined with other chemical agent to form complexes that may be only slowly
soluble in body fluids
 The slow dissolution provides the extended release of the drug;
Clinical Considerations
❖ Patients should be advised of the dose and dosing frequency of modified drug-release products and
instructed not to use them interchangeably or concomitantly with immediate-release forms of the same
drug.
❖ Patients should be advised that modified- release tablets and capsules should not be crushed or
chewed, since such action would compromise their drug release feature
❖ Patients and caregivers should be advised that nonerodible plastic matrix shells and osmotic tablets
remain intact throughout gastrointestinal transit and the empty shells or ghosts from osmotic tablets
may be seen in the stool.
Packaging
� Well closed and tight container
� Light resistant container

NON-ORAL MODIFIED-RELEASE SYSTEMS

1. OCULAR INSERTS
 Ocusert (Ocular Pilocarpine therapeutic system which releases medication over a 7-day period in the
treatment of glaucoma)
 Lacrisert (for the treatment of dry eyes)
2 PARENTERAL SYSTEMS
 Depo-Provera Contraceptive Injection
 Depot Vit B 12
 Penadur LA
3. VAGINAL INSERTS
 Cervidil Vaginal insert – contains dinoprostone for the induction of labor
 Crinone Gel – contains progesterone used to assist reproduction
 Estring – vaginal ring containing estradiol for the treatment of urogenital symptoms associated with
postmenopausal atrophy of the vagina
4. SUBDERMAL IMPLANT
 Solid dosage form designed to be inserted under the skin by special injectors or by surgical incisions
 Zoladex Implant (Zeneca) – contains goserelin acetate for the treatment of advanced prostatic cancer
 Norplant System (Wyeth-Ayerst) – contains levonorgestrel that provides up to 5 years contraception

TRANSDERMAL DRUG DELIVERY SYTEMS (TDDS)

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 also known as transdermal patches
 Controlled release devices containing the drug for systemic absorption after topical application to the skin
surface
TDDS COMPONENTS
Backing film Protect the system from environmental entry and from loss of drug from the system
or moisture from the skin
Drug Reservoir/ Active ingredients
matrix To store and release the drug at the skin site
Adhesive Serves to bind the components of the patch to the skin
(polymer) Maintain contact with the skin after application
Membrane Controls the release of the drug from the reservoir in certain types of patches
Liner Protects the drug during storage and is removed prior to use

Factors affecting Transdermal Absorption

 Drug concentration
 Area of application
 Physicochemical attraction to the skin
 Drugs with molecular weights and lipid water solubility
 Hydration of the skin
 Horny layer of the skin
 Contact Time
ADVANTAGES OF TDDS
 Avoid GI absorption difficulties and incompatibilities
 Substitute for oral administration of drug when the route is unsuitable
 Avoid first-pass effect
 Avoid the inconvenience of parenteral therapy
 Provide extended therapy with single application
 Provide extended activity of drugs having short half-lives
 Drug therapy may be terminated rapidly
 Rapid identification of medication in emergencies

DISADVANTAGES OF TDDS
 Only potent drugs are suitable for transdermal drug delivery
 Some patients may develop contact dermatitis due to one or more of the system components

General Clinical Consideration in the use of TDDS

 Percutaneous absorption may vary with the site of application
 TDDSs should be applied to clean, dry skin that is relatively free of hair and not oily, irritated, inflamed,
broken, or callused.
 Use of skin lotion should be avoided at the application site
 TDDSs should not be physically altered by cutting
 TDDS should be removed from its protective package, with care not to tear or cut into the unit
 TDDS should be placed at a site that will not subject it to being rubbed off by clothing or movement
 TDDS generally may be left on when showering, bathing, or swimming
TDDS should be worn for the full period stated in the product’s instructions.
The patient or caregiver should be instructed to cleanse the hands thoroughly before and after applying
a TDDS.
 Reevaluate the patient in case of sensitivity or intolerance, or undue skin irritation to the TDDS
Upon removal, a used TDDS should be folded in half with the adhesive layer together so that it cannot
be reused.
EXAMPLES OF TDDS
o TRANSDERMAL SCOPOLAMINE- antinauseant
o TRANSDERMAL NITROGLYCERIN – used in prophylactic treatment of angina
o TRANSDERMAL CLONIDINE – for hypertension
o TRANSDERMAL NICOTINE – adjuncts in smoking cessation
o TRANSDERMAL ESTRADIOL/Transdermal Contraceptive System (Ortho Evra- Norelgestromin, ethinyl
estradiol)
o TRANSDERMAL TESTOSTERONE
o OTHER TRANSDERMAL THERAPEUTIC SYSTEMS
a. Cardiovascular agents: Diltiazem, Isosorbide dinitrate, Propranolol, Mepindolol and Verapamil
b. For hormonal contraception: Levonorgestrel/Estradiol

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c. For Alzheimer’s disease: Physostigmine and Xanomeline; For substance addiction: Naltrexone and
Methadone
d. For anxiety: Buspirone; For smoking cessation: Bupropion; For impotency: Papaverine

SUPPOSITORIES INSERTS AND STICKS

SUPPOSITORIES
 Are solid dosage forms intended for insertion into the body orifices where they melt, soften, or dissolve
and exert localized or systemic effects
TYPES OF SUPPOSITORIES

Local Action
• Once inserted , it will melt, soften, or dissolve, distributing its medicaments to the tissue of the region.
Rectal Vaginal Urethral
▪ Constipation • Contraceptives (nonoxynol • Antibacterial
▪ Relive pain, irritation, 9) • Local anesthetics for
itching and inflammation • Antiseptic in feminie urethral examination
associated with hemorhoids hygiene
and anorectal conditions • Combat invading pathogen
▪ Laxative (glycerin) (Trichomonacides,
Antifungal,
Antibiotics,
Anti-infectives)

Factors affecting the absorption of drugs from rectal suppositories

Physiologic Factor
(1) Circulation route
Drugs absorbed in the rectum bypass the first pass effect in the liver instead of being absorbed into the
general circulation
Lymphatic circulation also assist in the absorption of rectally administered drug
(2) pH and Lack of buffering capacity of the rectal fluids
Rectal fluids are essentially neutral in pH and have no effective buffer capacity, the form in which the
drug is administered will not generally be chemically changed by the rectal environment.
(3) Colonic content
It is more effective for a drug to absorbed systematically in an empty rectum than from one that is
distended with fecal, diarrhea, tissue dehydration can influence the rate and degree of absorption at the
rectal site
Physicochemical Factor
(1) Lipid-water solubility
A lipophilic drug that is distributed in a fatty suppository base in low concentration has less of a
tendency to be released into the body fluid, than in a fatty base
(2) Particle size
Smaller particle size the more readily the dissolution of the particle and the greater chance for rapid
absorption
(3) Nature of the base
Base must be capable of melting, softening or dissolving it release its absorption
If the base interacts with the drug to inhibit its release, drug reaction will be impaired or prevented

SUPPOSITORY BASES
1. BASES THAT MELT – FATTY OR OLEAGINOUS BASES
 COCOA BUTTER (Theobroma oil); melts at 30-36C
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  Good base for rectal suppositories but less ideal for vaginal and urethral supp.
 Disadvantage: exhibit polymorphism=> crystals
 Must be slowly and evenly melted in water bath to avoid crystallization
 Phenol and chloral hydrate-lowers melting pt
 Cetyl esters wax (20%) or beeswax (4%)- solidifying agent
 WITEPSOL BASES – triglycerides of saturated fatty acids (lauric acid)
 WECOBEE BASES – triglycerides derived from coconut oil
 FATTIBASE® - triglycerides from palm, palm kernel, and coconut oils with self emulsifying glyceryl
monostearate and polyoxyl stearate
 Hydrogenated fatty acids of vegetable oil (palm kernel oil and cottonseed oil)
 Fat based with glycerin and high MW fatty acids (palmitic and stearic acids; glyceryl monosterate and
glyceryl monopalmitate)

2. BASES THAT DISSOLVE - Water soluble and water miscible bases

 PEG POLYMERS
 Use combination of different MW’s PEG polymers: PEG 400 –liquid; PEG 1000 – semisolid;
PEG 1500 to 1540 – fairly firm semisolids; PEG 4000 to 6000 – wax-like
 Do not “leak” from the orifice
 PEG less than 20% water should be dipped in water prior to use
 Do not melt at body temperature but rather dissolved slowly in the body’s fluid
 GLYCERINATED GELATIN - Frequently used in vaginal suppositories
 Tends to absorb moisture, has dehydrating effect and irritates tissue upon insertion (moist prior
to insertion)
3Miscellaneous
• Mixture of oleaginous and Water soluble and water miscible
• Polyoxyl 40 stearate

Preparation of suppositories
a. HAND ROLLING b. COMPRESSION c. FUSION METHOD - Molding from a melt
• Molding from a melt - most frequently used (fusion method)
• Hand rolling and shaping - oldest and simplest method, by rolling the suppository into the desired
shape. The mass is then rolled into a cylindrical rod of desire length and diameter
• Compression - cold mass of the base containing the drug is compressed into suppositories by
using compression into the desired shape.

Packaging and Storage

 COCOA BUTTER BASED SUPPOSITORIES - Individually wrapped; refrigerated
 GLYCERIN SUPP. AND GLYCERINATED GELATIN BASED SUPPOSITORIES - Packaged in a tightly
closed containers; stored at controlled room temperature
 PEG BASED SUPPOSITORIES - Stored at usual room temperature without the requirement of
refrigeration
 Light sensitive drugs- individually wrapped, opaque materials like metallic foil or plastic
 Stored in high humidity- absorb moisture tends to become spongy
 Stored in extreme dryness may lose moisture and become brittle

Vaginal tablet
Adv: easy to manufacture; more stable; less messy
Usually ovoid packed with inserter
Prepared by tablet compression

Lactose - filler/diluent
Starch - disintegrant
Polyvinyl pyrrolidone - Dispersing agent
Magnesium Stearate - lubricant

Sticks
• Medicated sticks
• Administering topical drugs
• Cylindrical in shape ranging from 5 to 25g
• Packed in an applicator tube for topical administration and the applicator can be adjusted to
continually exposed new fresh sticks
• How to prepare
Same as preparing supp except that melt is poured into the administering device or tube

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 • Local anesthetics, sunscreens, oncology products, antiviral and antibiotics

OINTMENTS AND OTHER MEDICATED APPLICATIONS

Routes of application
Skin Nasal Vaginal Rectal Eyes

OINTMENTS
 Are semisolid preparations intended for external application of such consistency that they may be
readily applied to the skin with or without inunction (rubbing)
 Are typically used as: Emollients, Protective barriers and Vehicles

TYPES OF OINTMENTS
1. MEDICATED - those with medicaments for the treatment of cutaneous infections
 Examples: Sulfur Ointment, Zinc oxide Ointment, Whitfield Ointment, Compound Resorcinol
Ointment
2. NON-MEDICATED - Also referred to as “Ointment bases”
* Used as protectants, emollients or lubricants

Four General groups of OINTMENT BASES

1. HYDROCARBON BASES OR OLEAGINOUS BASE
 Water free
 Difficult to wash-off
 Retained on the skin for prolonged periods
 Do not permit the escape of moisture from the skin
 Has emollient effect and acts as occlusive dressing
 Petrolatum USP
o Yellow petrolatum
o Vaseline
o purified mixture of semi-solid hydrocarbons obtained from petrolatum.
 White Petrolatum
o White Vaseline
o is a purified mixture of semisolid hydrocarbons from petroleum that has been wholly or
nearly decolorized
 Yellow Wax
o purified wax obtained from the honeycomb of the bee
 White Wax
o Bleached yellow wax
 Yellow Ointment
o Yellow wax and Petrolatum
 White Ointment
o white wax (bleached and purified yellow wax) and white petrolatum

2. ABSORPTION BASES
 Are not easily removed from the skin with water washing
 Useful as pharmaceutical adjuncts to incorporate small volumes of aqueous solutions into hydrocarbon
bases

Types of ABSORPTION BASES

 Those that permit the incorporation of aqueous solutions, resulting in the formation of water-in-oil
emulsions
 Hydrophilic Petrolatum,USP
o White petrolatum combined with 8% beeswax, 3% stearyl alcohol and 3% cholesterol
 Aquaphor®
 Those that are already W/O emulsions that permit the incorporation of small additional quantities of
aqueous solutions
 Also called EMULSION BASES
 Lanolin, USP (Wool fat)
o Anhydrous Lanolin contains not more than 0.25% water
o Hydrous Lanolin- contains 25% moisture

3 WATER-REMOVABLE BASES
 Oil-in-Water emulsion resembling creams in appearance
 Are easily washed from the skin and are often called “WATER-WASHABLE” bases
 May be diluted with water or with aqueous solutions
 They have the ability to absorb serous discharges
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  Example: Hydrophilic Ointment, USP
Consists of methylparaben (0.25 g), propylparaben (0.15 g), sodium lauryl sulfate (10 g), propylene
glycol (120 g), stearyl alcohol (250 g); white petrolatum (250 g); and purified water (370 g) Sodium
lauryl sulfate – emulsifying agent; stearyl alcohol and white petrolatum – oleaginous phase;
methylparaben, propylparaben – antimicrobial preservatives; others – aqueous component

4 WATER-SOLUBLE BASES
 Commonly referred to as “greaseless” ointment bases
 Water-washable, because of the absence of oleaginous material
 Soften with the addition of large amount of aqueous solutions
 Example: Polyethylene Glycol Ointment,NF – contains PEG 3350 (40%) and PEG 400 (60%)

METHODS OF PREPARATION
(1) Incorporation-mixing of all ingredients
(2) Fusion
 All or some of the components of an ointment are combined by being melted together and cooled with
constant stirring until congealed
 Used for solid with high melting point
 Heat-labile substances and any volatile components are added last, when the temperature of the
mixture is low enough not to cause decomposition or volatilization of the components

Packaged in either large-mouth ointment jars or in metal or plastic tubes

Must be stored in a well-closed container and in a cool place.

CREAMS
 Are semisolid preparations containing one or more medicinal agents dissolved or dispersed in either a
water-in-oil (W/O) emulsion or an oil-in-water (O/W) emulsion or in another type of water-washable base.
 Are viscous liquids or semisolid emulsions either the Oil-in-Water (O/W) or Water-in-Oil (W/O) type
 Find primary application in topical skin products and in products used rectally and vaginally
 Easier to spread and remove than ointments
 Prepared by fusion method
 O/W CREAMS include Foundation Cream, Shaving Cream, Hand Cream and Vanishing Cream
 W/O CREAMS are Cold Cream – Petrolatum Rose Water Ointment and Emollient Cream

Cream • Prefer by patient

• less sticky
• Easy to spread and remove
• treating oozing or “wet” skin conditions.
• covering large areas of skin.
Ointment • best used on dry skin.
• ‘occlusive,’ which means they trap moisture and are not well absorbed
into the skin.
• keep the skin moist for longer periods of time.
• promote more complete absorption of the active ingredient or
medication.

GELS
 Are semisolid systems consisting of dispersions of small or large molecules in an aqueous liquid vehicle
rendered jelly-like by the addition of a gelling agent.
 Are sometimes called jellies.
 Gels contain
 gelling agent (e.g. synthetic macromolecules- carbomer 934; cellulose derivatives-
carboxymethylcellulose or hydroxypropyl methylcellulose and natural gums-tragacanth)
 Water
 drug substance
 Solvents
 antimicrobial preservatives
 stabilizers
 Medicated gels may be administered into the skin, the eye, the nose, the vagina, and the rectum
 Packaging and Storage-Tight Container; Avoid freezing
PASTES
 Thicker, stiffer and more absorptive and less greasy than ointments
 Effective employed to absorb serous secretions and therefore preferred for crusting and oozing lesions
 Not generally suited for application to hairy parts of the body
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 Example: Zinc oxide Paste –Lassar’s Plain Zinc Paste(25% ZnO and starch with white petrolatum)

PLASTERS
 Are solid or semisolid adhesive masses spread upon a suitable backing material and intended for external
application to a part of the body to provide prolonged contact at that site
 Composed of backing material, adhesive material and medicinal substances
 May be MEDICATED or NON-MEDICATED
□ MEDICATED
✖ Salicylic Acid Plaster, 10 to 40% (Corn Plaster) – Keratolytic, for the removal of corns
✖ Chili Plaster
✖ Antiseptic Plaster
✖ Salonpas
□ NON-MEDICATED
🞑 Used to provide protection or mechanical support
🞑 Examples: Leukoplast, Micropore,Transpore, Bandages, Tegraderm Film

GLYCEROGELATINS
 Are plastic masses intended for topical application and containing gelatin (15 %), glycerin (40 %), water (35
%) and an added medicinal substance (10 %)
 Melted prior to application, cooled and applied with a fine brush
 Official glycerogelatin is ZINC GELATIN (Zinc Gelatin Boot) – used in the treatment of varicose ulcers

CATAPLASMS/POULTICES
 Are ointment like preparations intended for warm, external application to a body surface for the purpose of
reducing inflammation and/or allaying pain
 Should be warmed before application and applied with a piece of cloth;

LIQUID DOSAGE FORMS

SOLUTIONS
 are liquid preparations that contain one or more substances dissolved in water or co-solvent mixtures

TYPES OF SOLUTIONS
ORAL SOLUTIONS
 COMPONENTS are medicinal agents, flavorants, colorants, sweetening agents, stabilizers (glycerin or
sorbitol), preservatives, and vehicles
 ADVANTAGES are: Homogenous; Easier to swallow than the solid dosage forms; Onset of action and
bioavailability of drugs that have slow dissolution rate are improved
 DISADVANTAGES are: Bulky; Degrade more rapidly; More likely to interact with other constituents
Forms of Oral Solutions
 Dry powder for solution - dry powder for reconstitution prior to use
 Oral rehydration solution - available in liquid or powder/packet for reconstitution
 Oral colonic lavage solution- preaaration of the bowel for procedures
 PEG-ES (PEG 3350, sodium sulfate, sodium bicarbonate, sodium chloride, potassium chloride)
 The recommended adult dose 4 L drink 240 mL of solution every 10 minutes until 4 L is
consumed
 Magnesium citrate solution
 Colorless to slightly yellow clear effervescent liquid having a sweet acidulous taste and a lemon
flavor
 Synonyms citrate of magnesia
 Use: saline cathartic
 Sodium Citrate and Citric Acid Oral Solution
 Dose 10 to 30 mL four times a day
 Systemic alkalinizer

TOPICAL SOLUTIONS
• Topical solutions employ an aqueous vehicle, whereas the topical tinctures characteristically employ an
alcoholic vehicle.
• Components
– cosolvents or adjuncts to enhance stability or the solubility of the solute are employed.
– Most topical solutions and tinctures are prepared by simple solution method. Other solutions are
prepared by chemical reaction.
 Employ an aqueous vehicle; Should be labeled “FOR EXTERNAL USE ONLY”
 Aluminum acetate topical solution-Burow solution- astringent wash or wet dressing
 Aluminum subacetate topical solution-Modified Burow Solution- astringent wash and wet dressing

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  Calcium hydroxide topical solution- Limewater, liquor calcis- an astringent- employed in combination
with other ingredients in dermatological solutions and lotions
 Coal Tar Topical solution-Liquor Carbonis Detergens; Liquor Picis Carbonis; LCD20% coal tar and 5%
polysorbate 80-Local anti-eczematic used in external treatment of chronic skin conditions
 Hydrogen peroxide- Peroxide / agua oxinada- Contains 2.5 to 3.5% (w/v) H2O2- Local anti-infective for
use topically on the skin and mucous membrane
 Chlorhexidine gluconate- 4% (Hibiclins), used as a surgical scrub, hand wash, and skin wound and
general skin cleanser (can cause irritations) 12%- Antigingivitis, antiplaque, antimicrobial agent
 Povidone-Iodine Topical Solution- antiseptic; 10% solution employed as surgical scrub and nonirritating
antiseptic solution Ex. Betadine Solution
 Thimerosal- fungistatic- 0.1% thimerosal, used as bacteriostatic and mild fungistatic agent Merthiolate
Solution

OTIC SOLUTIONS - Ear or aural solutions

USES:
 For the removal of excessive cerumen; Examples: Cerumenex Ear drop, Debrox Drops
 For the treatment of ear infections, inflammation, or pain
Examples: Auralgan Otic Solution, Americaine Otic, Chloromycetin Otic, Corticosporin Otic, Otobiotic
solution, VoSol Otic Solution

NASAL SOLUTIONS
Administered in form of:
 drops (instillation)
 sprays
 aerosol (spray under pressure)

Inhalation solution- sterile drugs or sterile solution administered by the nasal or respiratory route
Vehicle used:
 Sodium chloride inhalation
 Sterile water for inhalation

Instrument used for inhalation therapy

 Atomizing unit in bulbous glass chamber
 Nebulizer
 Vaporizer
 Humidifier
• Inhalant- Inhalants are drugs or combinations of drugs that by virtue of their high vapor pressure
can be carried by an air current into the nasal passage, where they exert their effect. Ex. (amyl
nitrite inhalant, Propylhexedrine inhalant)
• The device that holds the drug or drugs and from which they are administered is an inhaler

 Afrin Nasal Drops and Nasal Spray, Nasalide and Privine Nasal Solution - Decongestant
 Beconase AQ Nasal Spray and Nasalcrom Nasal Spray – for the prevention and treatment of perrenial
allergic rhinitis
 Salinase and Ocean Mist – to restore moisture and relieve dry, crusted and inflamed nasal membrane
 Syntocinon Nasal Spray – employed for initial milk let-down preparatory to breast feeding
 Diapid Nasal Spray - antidiuretic

METHODS OF PREPARING SOLUTIONS

 SIMPLE SOLUTION METHOD - Example: Strong Iodine Solution
 SOLUTION BY CHEMICAL REACTION - Example: Magnesium Citrate Solution
 SOLUTION BY EXTRACTION

AROMATIC WATERS
 Are clear, saturated aqueous solutions of volatile oils or other aromatic or volatile substances
 A pleasantly flavored vehicle for water soluble drugs or an aqueous phase in an emulsion or suspension
 Addition of electrolytes may result to “salting-out” of the volatile ingredient
 Stored in a tight, light-resistant containers

METHODS OF PREPARATION
1. DISTILLATION
COHOBATION – the process of redistillation two or more times until the distillate becomes clear
19 | P a g e - C E U - D D S - J L E E
  SOLUTION METHOD – the volatile, or aromatic substance is admixed with water, with or
without the use of a dispersant (e.g. talc)
Problem: Salting out- formation of insoluble layer at the top upon addition of large amount of water-soluble
drugs

GARGLES
 Are solutions used to treat the pharynx and the nasopharynx by forcing air through the lungs thru the gargle
which is held in the throat
 Must be diluted with water prior to use; Examples: Phenol Gargle, Betadine Gargle, Bactidol

MOUTHWASHES
 Are aqueous solutions most often used for their deodorizing, refreshing and antiseptic effect.
 Often used cosmetically than therapeutically; Examples: Listerine, Astring-O-sol, Mouthwash, NF
OTHER WASHES - EYE WASH – Collyrium; NASAL WASH - Collunarium

DOUCHES
 Are aqueous solutions directed against a part or into a cavity of the body; Functions as cleansing or
antiseptic agent
 Usually administered into a body part using a bulb syringe
 Eye douche, Nasal douche, Pharyngeal douche and Vaginal Douche (may be prepared from powders or
from liquid solutions or liquid concentrates and is used for irrigative cleansing of the vagina)

ENEMAS
 Are RECTAL INJECTIONS employed to: Evacuate the bowel; Influence the general system by absorption;
Affect locally the seat of disease; Visualize the GIT for diagnosis
 TYPES OF ENEMA
o EVACUATION ENEMA - Used to cleanse the bowel (Fleet enema®+)
o RETENTION ENEMA - Nutritive enema, Medicated enema and Diagnostic enema (Barium Sulfate
Enema)

SYRUPS
 Are concentrated, aqueous preparations of a sugar or sugar substitutes with or without added flavoring
agent and medicinal substances

CLASSIFICATION
A. Medicated Syrups syrup + Active Ingredients
B. Non-Medicated Syrups or Flavored vehicle
Cherry and Orange Syrups – good vehicle for drugs requiring acid medium
Cocoa Syrup – effectively masks bitter tasting drugs
Ora-Sweet and Ora-Sweet SF – alcohol free vehicle for extemporaneous compounding of syrup
Raspberry Syrup – used to disguise salty or sour taste of drugs
Syrup, NF or Syrup, USP

Components of Syrup
 Sugar (sucrose or sugar substitute- sweetness and viscosity)
 Preservatives ( benzoic acid, sodium benzoate, combination of methylparaben propylparaben
and butylparaben, alcohol 15% to 20%)
 Flavorant (natural or synthetic)
 Colorant (correlates with the flavorant employees)
 Co solvents
 Solubilizing agent
 Thickeners
 Stabilizers
 active ingredients

SYRUP, NF (SIMPLE SYRUP)- 85g to make 100mL of water (46.3mL of water)

 A concentrated or nearly saturated aqueous solution of sugar (85% w/v, 65% w/w); Specific gravity =
1.313
 Have low solvent capacity for water-soluble drugs
 Self-preserving, however diluted syrups are prone to microbial contamination thus require additional
preservative (i.e. parabens)
 Saturated solutions tend to undergo crystallization (Syrup, USP – minimal tendency to undergo
crystallization)

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Methods of preparing syrups
1. solution with the aid of heat - excessive tends to cause inversion of sucrose
2. solution by agitation without the aid of heat
3. addition of sucrose to a medicated liquid or to a flavored liquid
4. percolation - May be used to prepare Simple Syrup and Ipecac syrup

ELIXIRS
 Are clear, sweetened, hydroalcoholic solutions intended for oral use, and are usually flavored to their
palatability
 Alcohol Content vary from 5 – 40 %
✔ 10 to 12% - self preserving
✔ low-alcoholic elixir, (8% to 10% alcohol)
✔ high-alcoholic elixir, (73% to 78% alcohol)
✔ iso-alcoholic elixir-mixing of low and high
• Most elixirs become turbid when moderately diluted by aqueous liquids.
• Elixirs are not the preferred vehicle for salts because alcohol accentuates saline taste
 COMPONENTS: Alcohol and water (primary solvents); Adjunct solvents (glycerin and propylene glycol),
Sweeteners, Flavorants and colorants, and Medicinal substances

Advantages
 Maintain both water-soluble and alcohol-soluble components in solution
 Stable and Easy to prepare (by simple solution method)
Disadvantages
 Less effective in masking the taste of drugs because elixirs are less sweet and less viscous
 Not recommended for children due to their alcohol content

CLASSES OF ELIXIRS
 NON-MEDICATED ELIXIRS
o Employed as vehicles; Examples: Aromatic Elixir, NF; Isoalcoholic Elixir; Compound
Benzaldehyde Elixir
 MEDICATED ELIXIRS
o Examples: Diphenhydramine Elixir; Phenobarbital Elixir; Digoxin Elixir
Preparation of Elixirs
• By simple solution with agitation
• By admixture of two or more liquids ingredients
STORAGE: Tight, light-resistant containers and protected from excessive heat

SPIRITS OR ESSENCES
 Are alcoholic or hydroalcoholic solutions of volatile substances
 High alcohol content, usually over 60%, maintains water-insoluble volatile oils in solution
 Addition of water results to the separation of the oil

Uses of Spirits
 MEDICINAL SPIRITS - AROMATIC SPIRIT OF AMMONIA (a reflex stimulant)
 FLAVORING SPIRITS - Compound Orange Spirit, Compound Cardamom Spirit
How administered?
 Taken orally (Brandy and Whisky) - mixed with a portion of water to reduce pungency of the spirit
 Applied externally
 inhalation (Aromatic spirit of ammonia)
Methods of Preparation
 Distillation - Brandy (48 – 54 % alcohol) and Whisky (47 – 53% alcohol)
 Solution with Maceration - Peppermint Spirit
 Solution by Chemical Reaction - Ethyl Nitrite Spirit
 Simple Solution - Ammonia Spirit (Spirit of Sal Volatile)

LINIMENTS (EMBROCATIONS)
 Are alcoholic or oleaginous solution or emulsion of various medicinal substances intended for external
application to the skin, generally with rubbing
 Must bear a label indicating “FOR EXTERNAL USE ONLY” or “ Not to be applied to broken skin”

TYPES OF LINIMENTS
 Alcoholic Liniments - used for its rubefacient property [ PAO liniment]
 Oily Liniments - useful when massage is required [ Efficascent Oil]
 Emulsion Liniment [ White Liniment, Camphor Liniment, Omega Pain Killer]
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COLLODIONS (Ethereal solutions)
 Are liquid preparations composed of pyroxillin (nitric and sulfuric acids)) dissolved in a solvent mixture
usually composed of 3:1 alcohol and ether with or without added medicinal substances
 Intended for external use only
 Applied to the skin with a fine camel’s hair brush or glass applicator
 Stored in a tight-closed container at a temperature not exceeding 30°C remote from fire

Examples and Uses of Collodions

 COLLODION, USP - useful in holding the edges of an incised wound together
 FLEXIBLE COLLODION, USP - prepared by adding 2% camphor and 3% castor oil
o The castor oil renders the product flexible
o camphor makes the product waterproof
o coating over bandages or stitched incisions to make them waterproof and to protect them from
external stress
 SALICYLIC ACID COLLODION, USP - a 10% salicylic acid in Flexible Collodion; used as a keratolytic
agent

GLYCERITES
 Are viscous solutions or mixtures of medicinal substances in NOT LESS THAN 50% by weight of
GLYCERIN
 Used as a medicinal agent or as an aid in dissolving other drugs in water or alcohol
 Examples: Starch glycerite - topical protectant; Tannic Acid glycerite – astringent; Phenol glycerite
FORMULATION COMPONENTS:
1. Glycerin – nlt 50% w/w
2. Purified water
3. Gelatin
4. Medicament (active ingredient)

TOOTHACHE DROPS
 Preparations used for the temporary relief of toothache
 Applied using a small pledget of cotton saturated with the product into the tooth cavity
 Contains clove oil and mixtures of phenol with camphor or creosote

TINCTURE
 Are alcoholic or hydroalcoholic solutions of chemicals or soluble constituents of vegetable drugs
o Alcohol content varies from as low as 15% to as high as 80%

VARIATIONS OF OFFICIAL TINCTURES

As to the method of preparation:
 By Extraction method
o Maceration method - Compound Benzoin Tincture
o Percolation method - Belladona Tincture and Vanilla Tincture
 By Simple Solution method – employed for tinctures of chemical substances (Iodine Tincture and
Thimerosal Tincture)
As to strength of their active ingredient:
 Tinctures potent drugs – 10 % in strength (Belladonna Tincture)
 Tinctures prepared from non potent drugs – 20 % in strength (Tolu Balsam Tincture)
 Tinctures prepared from undried fresh fruit peel – 50 % in strength (Sweet Orange Peel Tincture)
As to their intended use in pharmacy and medicine:
 MEDICATED
o ORAL TINCTURES
 Disadvantages: Unpleasant tasting ; High alcohol content
 Examples are Paregoric Tincture (Camphorated Opium Tincture) –diarrhea
 Belladona Tincture - arthritis; irritable bowel syndrome
o TOPICAL TINCTURES
 Can cause stinging sensation when applied to abraded or broken skin
 Examples:Compound Benzoin Tincture – topical protectant; Iodine Tincture – germicide;
Thimerosal Tincture - antiseptic
 NON MEDICATED – used as flavoring agents
 Examples: Vanilla Tincture, Sweet Orange Peel Tincture, Tolu Balsam Tincture

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As to alcohol content: Contains approximately 15 – 80 % alcohol
 Opium Tincture – 17 to 21 % alcohol
 Compound Benzoin Tincture – 74 to 80% alcohol
 Iodine Tincture – 44 to 50% alcohol
 Thimerosal Tincture – about 50% alcohol

 Aging can cause the precipitation of the inactive constituents in tinctures

 Glycerin may be added to increase the solubility of the active constituents and reduce precipitation
during storage
 Stored in a light-resistant containers

EXTRACTIVES (TINCTURES, FLUIDEXTRACTS, EXTRACTS)

METHODS OF EXTRACTION
• MACERATION - to soak
• PERCOLATION- strain slow passage of a suitable solvent through a column of the drug
• INFUSION- vegetable drugs are extracted of their water-soluble constituents by steeping or drenching
them in water
• DIGESTION- form of maceration in which gentle heat (40-600C) is applied to the drug menstruum
mixture and maintained throughout the extraction to increase the solvent powers of the menstruum
• DECOCTION-process of boiling vegetable substances with water to extract the soluble principles

FLUIDEXTRACTS
 Are liquid extracts of vegetable drugs that contain alcohol as a solvent, preservative, or both
 Prepared by Percolation
 Sometimes referred to as “100% tinctures”
 Are considered too potent for self administration, and too bitter
 Used today as sweetening or flavoring agents

EXTRACTS
 Concentrated preparations of vegetable or animal drugs obtained by removal of the active constituents of
the respective drugs with suitable menstrua, evaporation of all or nearly all of the solvent, and adjustment of
the residual masses or powders to the prescribed standards

THREE FORMS OF EXTRACTS

 SEMI-LIQUID EXTRACTS - syrupy consistency
 PILULAR OR SOLID EXTRACTS - plastic consistency; preferred in compounding ointments or pastes
 POWDERED EXTRACTS – dry; preferred in compounding powders, tablets, and capsules

DISPERSE SYSTEM
 Liquid preparations containing undissolved or immiscible drug distributed throughout a vehicle. In these
preparations.
o Dispersed phase -the substance distributed
o dispersing phase or dispersion medium - vehicle
o Dispersing agent- third component

Particle size
 Colloidal dispersion – 1 nm to 0.5 μm
 Coarse dispersions (suspensions and emulsions) – 10 um to 50 um
 Fine dispersions ( magmas and gels) – 0.5 um to 10 um

 Remember the “Shake Well” instruction before administering suspensions / emulsions.

SUSPENSION
 A two-phase system consisting of finely divided solid (suspensoid) dispersed in a liquid vehicle.

COMPOSITION
o Dispersed phase- suspensoid
o Dispersion medium- liquid
o Dispersing agent- suspending agent

SUSPENSING AGENT
— Also known as thickening agent
— Used to stabilize suspensions
— Help in lowering the sedimentation rate of particles in suspension
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 HYDROPHILIC COLLOIDS
o Increase the viscosity of water by binding water molecules; Support the growth of microorganisms
o Mostly anionic, except methylcellulose (neutral) and chitosan (cationic)
o Incompatible with quaternary antibacterial agents; Mostly are insoluble in alcoholic solutions
o Examples of Hydrophilic Colloids
Natural
 Acacia –used for internal preparation
 Tragacanth – better than acacia used for external and internal
Synthetic
 Methylcellulose and Carboxymethylcellulose
 INORGANIC SALTS
o CLAYS
o Bentonite (thixotropic nature)
o Magnesium Aluminum silicate (Veegum)
o Aluminum hydroxide

 OTHER AGENTS - Agar, chondrus (carrageenan),gelatin, pectin, gelatinized starch

TYPES OF SUSPENSION
 ORAL SUSPENSIONS
o Ready to use
o Dry powders for reconstitution
 SUSPENSIONS FOR INJECTION - Particles must exhibit “ syringebility”
 OPHTHALMIC SUSPENSIONS - Particle size must not exceed 10 microns
 SUSPENSIONS FOR TOPICAL USE
 Fine particles are desired to avoid grittiness when applied to the skin
 The smaller the particle size, the greater the covering and protective power of the preparation

Packaging and Storage of Suspension

• Should be packaged in wide-mouth containers having an adequate airspace above the liquid to
permit thorough mixing by shaking and ease of pouring
• Stored in a tight containers
• Must be protected from freezing, excessive heat, and light

CLASSES OF SUSPENSION
A. LOTIONS
B. GELS
C. MAGMAS AND MILKS
D. MIXTURES

LOTIONS - Suspensions for external application

■ A low to medium viscosity, topical product, intended to be applied on “unbroken” skin.
■ Lotions have lower viscosity than Creams and Gels.

Methods of Preparation
 Trituration method
 By chemical reaction method

Types of lotions
 MEDICINAL LOTIONS
o CALAMINE LOTION – antipruritic; use to relieve itching and pain of sunburn, insect bites and
other minor irritations
o BENZYL BENZOATE LOTION – used for scabies
o PHENOLATED CALAMINE LOTION – anesthetic and antiseptic
o WHITE LOTION – for the treatment of acne and antiseptic
 COSMETIC LOTION
o Are applied to hair, scalp, face and hands; Popular as sunscreen preparations

GELS
 Are semisolid systems consisting of either suspensions made up of small inorganic particles or large
organic molecules enclosed and interpenetrated by a liquid

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TERMINOLOGIES RELATED TO GELS
 Imbibition – taking up a certain amount of liquid without a measurable increase in volume
 Swelling – taking up of a liquid by a gel with an increase in volume
 Syneresis – the dispersion medium is squeezed out in droplets upon standing, and the gel shrinks
 Thixotropy- irreversible gel-sol formation with no change in volume or temperature
 Xerogel- the gel shrinks and only the framework remains

PREPARATION OF GELS
 BY CHEMICAL REACTION METHOD AND BY SIMPLE HYDRATION
 Aluminum hydroxide Gel can be prepared by both methods
o Aluminum hydroxide Gel, USP - Antacid
o Sodium Flouride and Orthophosphoric Acid Gels – Applied to teeth as dental prophylactic
o Aluminum Phosphate Gel - Antacid

MAGMAS AND MILKS

 Are aqueous suspensions of insoluble inorganic drugs and differ from gels mainly that the suspended
particles are larger
 USES OF MAGMAS AND MILKS
- Suspending agent for internal and external use – Bentonite Magma
- As medicinal antacid – Milk of Magnesia (prepared by methods similar to gels)
 Methods of Preparation
o Hydration-milk of magnesia
o Chemical reaction

MIXTURES
 Are aqueous liquid preparations which contain suspended insoluble solid substances and are intended
for internal use; Less viscous
Examples: Kaolin Mixture, Kaolin Mixture with Pectin, Brown Mixture

EMULSION - a two-phase system consisting of at least one immiscible liquid intimately dispersed in another in
the form of droplets

PHASES OF EMULSIONS
 DISPERSED PHASE – the liquid droplet, internal phase, or discontinous phase
 DISPERSION MEDIUM – external, or continous phase

TYPES OF EMULSION
W/O emulsion – if water is the internal phase
O/W emulsion – if water is the external phase
Microemulsion- most stable, single phase

EMULSIFYING AGENTS - Any compound that lowers the interfacial tension and forms a film at the interface
[NATURAL]-vegetable source
 acacia-used in the preparation of extemporaneous emulsions
 Tragacanth & agar- commonly employed as thickening agents in acacia-emulsified products
 Chondrus-thickening agent; used with acacia in cod liver oil emulsion
 Pectin- acts as an emulsion stabilizer in acacia emulsion
 Starch- used in preparation of enema
 These materials form hydrophilic colloids, which, when added to water, generally produce o/w emulsions

[NATURAL]-animal source
 Protein substances, such as gelatin, egg yolk, and casein,
 These substances produce o/w emulsions.
 The disadvantage of gelatin as an emulsifier is that the emulsion frequently is too fluid and becomes more
fluid upon standing.

[SEMI-SYNTHETIC]
 Methyl cellulose
o Used as suspending/thickening agents
 sodium carboxymethyl cellulose
o Used as emulsion stabilizer
o Used as suspending/thickening agents

Cholesterol
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 o High molecular weight alcohols, such as stearyl alcohol, cetyl alcohol, and glyceryl
monostearate.
o Primarily as thickening agents and stabilizers for o/w emulsions of certain lotions and ointments
used externally.
o Cholesterol and cholesterol derivatives may also be employed in externally used emulsions to
promote w/o emulsions.
Carbowaxes (PEG)- used to prepare cream and ointments
Lecithin
o Form w/o emulsion
o Rarely used as they darken the preparation

Synthetic emulsifying agents – anionic, cationic, or nonionic

o ANIONIC AGENTS – include sulfuric acid esters, sulfonic acid derivatives, and soaps
o Alkali soaps – form O/W emulsion;
o Metallic soaps – form W/O emulsion;
o Monovalent and polyvalent soaps – form W/O emulsion
o CATIONIC AGENTS - Used as surfactant in 1% concentration; Benzalkonium chloride
o NONIONIC EMULSIFIERS
o Resistant to the addition of acids and electrolytes
o Sorbitan esters – Spans, hydrophobic, low HLB values, form W/O emulsions
o Polysorbates – Tweens, hydrophilic, high HLB values, form O/W emulsions

HLB SYSTEM - Used to classify surfactants

HYDROPHILIC SURFACTANTS- High HLB values (>10); Form O/W emulsion
LIPOPHILIC SURFACTANTS - Low HLB values (1-10); Form W/O emulsion
HLB VALUE RANGE SURFACTANT APPLICATION
1–3 Antifoaming agents
4–6 Water-in-Oil emulsifiers
7–9 Wetting agents
8 – 18 Oil-in-Water emulsifiers
13 – 15 Detergents
10 – 18 Solubilizing agents

Methods Of Preparation
1. WET GUM METHOD (English method) - 4:2:1 of oil:water:gum
2. DRY GUM METHOD (Continental method)
3. BOTTLE METHOD – 3:2:1 OR 2:2:1 ratio of oil:water:gum
4. NASCENT SOAP METHOD
- The soap is formed first by mixing equal volumes of oil and alkali
- The soap acts as emulsifying agent; A 50:50 ratio of oil to water ensures sufficient emulsion
- calcium soaps and soft soaps.
- Calcium soaps are w/o emulsions that contain certain vegetable oils, such as oleic acid, in combination
with limewater
- They are prepared by mixing equal volumes of oil and lime water
Oil phase- olive oil( fatty acid is oleic acid)
Water phase- lime water(freshly prepared)
Emulsifying agent Calcium salts
Method use bottle method
Mortar method: when it contains zinc oxide and calamine

Theories Of Emulsification
o SURFACE-TENSION THEORY
 The use of surfactants result in the lowering of interfacial tension between two immiscible liquids
o ORIENTED WEDGE THEORY
 This theory assumes monomolecular layers of emulsifying agent curved around a droplet of the
internal phase
o PLASTIC OR INTERFACIAL FILM THEORY
 This theory places the emulsifying agent at the interface between the oil and water, surrounding the
droplets of the internal phase as a thin layer of film adsorbed on the surface of the drops

Methods Of Determining The Type Of Emulsion

o DYE SOLUBILITY TEST – uses methylene blue or brilliant blue
 If the dye is dissolve and uniformly diffuse – O/W;
 If the particle of the dye lie in dumps on the surface – W/O
26 | P a g e - C E U - D D S - J L E E
o DILUTION TEST
 If freely mixes with water – O/W;
 If not diluted with water – W/O
o ELECTRIC CONDUCTIVITY TEST
 O/W conducts electric current;
 W/O do not conduct electric current

AEROSOLS
o Pressurized dosage forms designed to deliver drug systemically or topically with the aid of a liquefied or
propelled gas (propellant)
o Aerosol container is known as PRESSURIZED PACKAGE
o Aerosol products may be designed to expel their contents as a fine mist; a coarse, wet, or dry spray; a
steady stream; or a stable or a fast-breaking foam.

Types of Aerosol
(1) Inhalation aerosols, commonly known as metered-dose inhalers (MDIs), are intended to produce fine
particles or droplets for inhalation through the mouth and deposition in the pulmonary tree.
(2) Nasal aerosols, commonly known as nasal MDIs, produce fine particles or droplets for delivery through
the nasal vestibule and deposition in the nasal cavity.
(3) Lingual aerosols are intended to produce fine particles or droplets for deposition on the surface of the
tongue.
(4) Topical aerosols produce fine particles or droplets for application to the skin.

COMPONENTS OF AEROSOL PRODUCT:

Product concentrate
o Active ingredients
o Anti-oxidant
o Surfactants
o solvents
Propellant
o Compressed gases
 Carbon dioxide
 Nitrogen
 Nitrous oxide
o Liquefiable gases
 CFC
 Trichloromonofluoromethane
 Dichlorodidifluoromethane
 dichlorotetrafluoroethane

ADVANTAGES:
o medication may be easily withdrawn from the package without contamination or exposure to the remaining
material
o the aerosol container protects medicinal agents adversely affected by atmospheric oxygen and moisture
o Topical medication may be applied in a uniform thin layer to the skin without anything else touching the
affected area
o The use of metered valves, dosage may be controlled.
o Aerosol application is a clean process, requiring little or no washup by the user

DISADVANTAGE: Environment hazard

o Aerosols are costly preparations
o Some propellant are very toxic
o The cooling effect of highly volatile propellants may cause discomfort on injured skin
o Aerosol packs should be kept from high temperature and fire because it may develop high pressure inside
the container leads to explosion

Methods of Filling Aerosols

I. Cold Filling - Product concentrate and propellant are cooled at -34.5 to -40°C
II. Pressure Filling

METERED DOSE INHALERS (MDI’s)

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o These devices allow a drug to be inhaled as a fine mist of drug or drug-containing particles for systemic or
pulmonary delivery
o Use special metering valves to regulate the amount of formulation and the drug that is dispensed in each
dose.
o Commonly employed in asthma therapy

STERILE DOSAGE FORMS (Parenterals, Biologicals, Irrigation Fluids, Dialysis Solutions, Pellets or
Implants and Ophthalmic Preparations)

PARENTERALS- refers to injectable routes of administration; Sterile, pyrogen-free preparations

Considerations
o Sterility
 A biologic indicator is a characterized preparation of specific microorganisms resistant to a particular
sterilization process
 STEAM & ETHYLENE OXIDE - bacillus stearothermophilus
 DRY - Bacillus subtilis
 IONIZING RADIATION - Bacillus pumilus, G. stearothermophilus, and B. subtilis
o Pyrogen Free
 Healthy rabbits
 Limulus amebocyte lysate (LAL)
o Isotonic
o Prepared In Environmentally Controlled Area
o Packaged In Special hermetic container
o Use of colorants is strictly prohibited

o LVP – pH and tonicity of the fluids should be physiologically compatible with the body fluids
o SVP – fluids need not be isotonic with the body fluids since the large volume of blood and other body
fluids rapidly dilutes them

OFFICIAL TYPES OF INJECTIONS

TYPES EXAMPLE
1. Injection Insulin Injection, USP
2. For injection Cefuroxime for Injection, USP
3. Injectable emulsion Profopol, USP
4. Injectable suspension Methylprednisolone Acetate Suspension, USP
5. For injectable suspension Imipenem and Cilastatin for Injectable Suspension, USP

Parenteral Route of Administration

◦ joints (intraarticular)
◦ joint fluid area (intrasynovial)
◦ Spinal column (intraspinal)
◦ spinal fluid (intrathecal),
◦ arteries (intra-arterial),
◦ heart (intracardiac)
◦ vein (intravenous, IV)
◦ a muscle (intramuscular, IM),
◦ into the skin (intradermal, ID; intracutaneous)
◦ under the skin (subcutaneous, SC; sub-Q, SQ; hypodermic

Advantages of IV drugs
◦ rapid action compared with other routes of administration
◦ Optimum blood levels may be achieved with accuracy
◦ In emergencies, IV administration of a drug may be lifesaving because of the placement of the drug
directly into the circulation and the prompt action
DISADVANTAGE
◦ once a drug is administered it cannot be retrieved.
◦ In the case of an ADR, the drug cannot be easily removed from the circulation
IM Route
◦ less rapid but generally longer lasting than those obtained from IV administration
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 ◦ Aqueous or oleaginous solutions or suspensions of drug substances may be administered
intramuscularly
SC Route
 used for injection of small amounts of medication
 Max amt to be injected 1.3mL
 Irritating drugs and thick suspension not suitable for sc injection
ID Route
 0.1ml for diagnostic

PHARMACEUTICAL SOLVENT WATERS

1. WATER FOR INJECTION, USP
 Conforms with the standards of Purified Water, USP but is also pyrogen-free
 Intended to be used in the manufacture of injectable products which are to be sterilized after their
preparation
 Intended to be used for 24-hours after its collection
2. STERILE WATER FOR INJECTION, USP –
 WFI that has been sterilized
 Packaged in single-dose containers of type I or type II glass that do not exceed the capacity of 1 liter
 Intended to be used as a solvent, vehicle or diluent for already-sterilized and packaged injectable
medications
3. BACTERIOSTATIC WATER FOR INJECTION, USP
 SWFI that contains one or more suitable bacteriostatic agents
 Packaged in pre-filled syringes or in vials containing NMT 30 mL
 Employed as a sterile vehicle in the preparation of small volumes of injectable preparations (in multiple-
dose vials)
 To be labeled “NOT FOR USE IN NEWBORNS”
4. Sodium Chloride Injection, USP
 Usually given as a 0.9% solution. Because it is isotonic with blood, this solution is called normal saline
solution (NSS).
 Frequently used as catheter or IV lines flush to maintain patency
 Used to reconstitute medication
5. Bacteriostatic Sodium Chloride Injection, USP
 Bacteriostatic Sodium Chloride Injection, USP, 0.9% is a sterile, isotonic solution.
 Frequently used as catheter or IV lines flush to maintain patency
 To be labeled “NOT FOR USE IN NEWBORNS
6. Ringer’s Injection
 Sodium Chloride, Potassium Chloride, Calcium Chloride
 As a plasma expander, electrolyte replenisher
7. Lactated Ringer’s Injection, USP
 Sodium Chloride, Potassium Chloride, Calcium Chloride and sodium lactate
 Electrolyte replenisher and systemic alkalinizer

NON-Aqueous Solvent
 Fixed vegetable oils
 corn oil, cottonseed oil, peanut oil, and sesame oil
 Glycerin
 Polyethylene glycols
 Propylene glycol
 Alcohol

STERILIZATION
◦ sterilization, as applied to pharmaceutical preparations, means destruction of all living organisms and
their spores or their complete removal from the preparation

METHODS OF STERILIZATION
Steam sterilization
 Employs “steam under pressure” in an AUTOCLAVE.
 Applicable to pharmaceutical preparations and materials that can withstand the required temperatures
and
 are penetrated but not adversely affected by moisture
 Uses 1210C at 15 psi for 20 minutes setting.

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Dry-heat sterilization
 Employs “convective heat” in OVENS.
 Less effective than steam sterilization.
 Uses 150°C to 170°C for hours.
 Dry heat is also an effective method for sterilizing glassware and surgical instruments.
 Dry heat is the method of choice when dry apparatus or dry containers are required, as in the handling
of packaging of dry chemicals or non-aqueous solutions

Sterilization by filtration
 Applicable to heat-labile parenterals.
 Involves removal of microorganisms by adsorption on a filter medium or by sieving mechanism.
 Uses a membrane filter or cellulose ester membrane filter

Gas Sterilization
 Applicable to sterile powders and plastic containers.
 The material is autoclaved first, then the gases are introduced.
 Uses the ff. sterilizing gases:
 Ethylene oxide
 Propylene oxide
 useful in sterilization of medical and surgical supplies and appliances such as catheters, needles, and
plastic disposable syringes

Sterilization by Ionizing Radiation

 Exposes the material to RADIATION – EMITTING
 ISOTOPES, such as;
 gamma rays
 cathode rays
 beta rays

SMALL VOLUME PARENTERALS

 Available in ampules, vials, or pre-filled syringes
 Package in single-dose or multiple-dose containers (2 mL to 30 mL)
 Examples: Heparin Sodium Injection, Insulin Injection, Lidocaine HCl Injection
LARGE VOLUME PARENTERALS
 Administered by intravenous infusion to replenish body fluids, electrolytes, or to provide nutrition
 Usually in volumes of 100 mL to 1 Liter
 Employed in
o maintenance therapy
 For the patient entering or recovering from surgery
 For patient who is unconscious and unable to take fluids, electrolytes and nutrition orally
 TPN (total parenteral nutrition) can be administered
o replacement therapy
 For patients who have suffered a heavy loss of fluid and electrolytes
IRRIGATION SOLUTION
 Are not injected into the vein but employed outside of the circulatory system
 Irrigation solutions are intended to bathe or wash wounds, surgical incisions, or body tissues

STERILE WATER FOR IRRIGATION, USP

 Same requirements as SWFI except in container design, particulate matter and labeling
 Labeling: “For Irrigation Only” and “ Not for Injection ”

DIALYSIS SOLUTION
 Peritoneal Dialysis solution- allowed to flow into the peritoneal cavity, used to remove toxic substances
normally excreted by the kidney
 Hemodialysis solution- is employes to remove toxins from the blood

BIOLOGICAL PRODUCTS
 Biologics for active immunity include vaccines and toxoids
 Biologics for passive immunity include Human Immune Sera and globulins and Animal Immune
 Stored in refrigerator (between 2°C and 8°C), or freezer with a temperature of -15°C
 Administered parenterally (IM, IV, SC and ID) but some are given orally
 Examples: MMR Virus vaccine, Tetanus toxoid, Tetanus antitoxin, Antivenin polyvalent, Smallpox vaccine,
Typhoid vaccine

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OPHTHALMIC PRODUCTS
Dosage Forms
 Solutions
 Suspension
 Gels
 Ointments
 Drug impregnated inserts
 Contact lenses and Contact lens care products

Special considerations for ophthalmic solutions and suspensions include:

 Sterility
 Most ophthalmic products cannot be sterilized by heat due to active principles or polymers used to
increase viscosity are not stable to heat
 By autoclave- not suitable for plastic and heat liable drug
 Bacterial filtration- not suitable for suspension
 Preservation
 Benzalkonium chloride
 benzethonium chloride
 Chlorobutanol
 phenylmercuric acetate
 phenylmercuric nitrite
 Isotonicity
 Lacrimal fluid is isotonic with blood having an isotonicity corresponding to that of 0.9% NaCl
solution (but)
 isotonicity limits of an ophthalmic solution in terms of sodium chloride or its osmotic equivalent may
range from 0.6% to 2% without marked discomfort to the eye.
 Some ophthalmic solutions are necessarily hypertonic in order to enhance absorption and provide
a concentration of the active ingredients strong enough to exert an effective action
 Buffering
Purposes of buffering
 For greater comfort to the eye
 To render the formulation more stable
 To enhance the aqueous solubility of the drug
 To enhance the drug’s bioavailability
 To maximize preservative efficacy
 Viscosity
Viscosity and Thickening
 Hydroxypropyl methylcellulose and polyvinyl alcohol are used as thickeners
 Ophthalmic solutions’ optimal viscosity is 15 to 25 cp.
 Viscosity of the product aids in maintaining the drug in contact with the tissues to enhance
therapeutic effectiveness
 Additional considerations
 Ophthalmic solutions must be sparkling clear and free of all particulate matter
 Drug particles in ophthalmic suspension must be finely divided to minimize eye irritation and/or
scratching of the cornea

 Packaging of Ophthalmic Solution and suspension

o packaged in small glass bottles with separate glass or plastic
o droppers, most are packaged in soft plastic containers with a fixed built-in dropper

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