Solutions & Oral

dosage forms
2

Pharmaceutical solutions

▸ Definition:
▸ Homogeneous mixture of two or more substances
▸ We will focus liquid solutions, with H2O or oil as
solvent

▸ Route of administration:
▸ Oral, IV, IM, SC, nasal, rectal, etc.
 Solutions
▸ In pharmaceutical terms, solutions are “liquid
preparations that contain one or more chemical
substances dissolved in a suitable solvent or mixture of
mutually miscible solvents” ( aqueous or non –aqueous).
▸ It may be classified as oral, otic, ophthalmic, or topical.
▸ Certain solutions prepared to be sterile and pyrogen free
and intended for parenteral administration are classified
as injections.
4

Solutions: many appellations

▸ Aromatic waters:
▹ Peppermint water, rosewater

▸ Aqueous acids:
▹ Diluted acids, Acetic acid, HCl(aq)

▸ Douches
▸ Enemas:
▹ Rectal or oral, Phosphate enema

▸ Gargles
▸ Mouthwashes
5

Solutions: many appellations

▸ Irrigation solutions:
▹ NS for irrigation
▸ Syrups:
▹ Concentrated sugar solution, Simple syrup (75% sucrose)
▸ Elixir:
▹ Used to contain EtOH
▸ Liniments:
▹ + organics, oil
▸ Spirits
▹ Aromatic ammonia spirit
Solutions can be formulated for different routes of
administration

Orally: Syrups, elixirs, drops

In mouth and throat: Mouth washes, gargles,
throat sprays.
In body cavities: Douches, enemas, ear drops,
nasal sprays.
On body Surfaces: Collodions, lotions.
7
8

Advantages
▸ Easy to dose from concentrate by simple dilution
▸ Easy to mix if necessary
▸ Easy to measure accurately
▸ Easy to administer orally to children and disabled persons
▸ More quickly effective than solid dosage forms
▸ Homogenous
▸ Dilute irritant action of some drugs
▸ Amenable to administration by any route
▹ Ex: suspension cannot be given IV
▸ No lag time due to dissolution
▹ Rapid onset of action
9

Disadvantages
▸ Solution chemistry poses many stability issues
▹ Physicochemical degradation
▸ Shelf life, storage requirement
▸ Bulky
▸ Unpleasant taste or odours are difficult to mask.
▸ Needs an accurate spoon to measure the dose.
▸ Less stable than solid dosage forms.
▸ Containers, tubing, etc.
▹ Shorter expiry than other dosage forms
▸ Additional sterility concerns
▸ Solubility may be limiting
▸ Need to mask taste (oral)
▹ Ex: suspension is “harder” to taste
Classification of Solutions According to Vehicle

(a) Aqueous solutions

(b) Non-aqueous solutions

What is the difference between aqueous and non
aqueous solution?

The key difference between aqueous and non

aqueous solution is that the solvent of an aqueous
solution is water whereas, in non aqueous solutions,
the solvent is any substance other than water. A
solution contains a solvent and solute (s).
 Pharmaceutical Solutions
Aqueous
1. Douches
Sweet &/or Viscid Nonaqueous
2. Enemas
3. Gargles 1. Syrups 1. Elixirs
4. Mouthwashes 2. Honeys 2. Spirits
5. Nasal washes 3. Mucilages 3. Collodions
6. Juices 4. Jellies 4. Glycerins
7. Sprays 5. Liniments
8. Otic solutions 6. Oleo Vitamin
9. Inhalations
Oral solutions
▸ their absorption from the gastrointestinal tract into
the systemic circulation may be expected to occur
more rapidly than from suspension or solid dosage
forms of the same medicinal agent.

▸ Solutes other than the medicinal agent are usually

present in orally administered solutions.

▸ These additional agents are frequently included to

provide color, flavor, sweetness, or stability.
▸ In formulating or compounding a pharmaceutical solution, the
pharmacist must use information on the solubility and stability
of each solute with regard to the solvent or solvent system.

▸ Combinations of medicinal or pharmaceutical agents that will

result in chemical and/or physical interactions affecting the
therapeutic quality or pharmaceutical stability of the product
must be avoided.

▸ For many medicinal agents, their solubility in the usual

solvents are stated in the United States Pharmacopeia–
National Formulary (USP–NF) as well as in other reference
books.
▸ Solubilizing agent or a different chemical salt form of the medicinal
agent, alteration of the pH of a solution, or substitution in part or in
whole of the solvent, a pharmacist can, in certain instances, dissolve
greater quantities of a solute than would otherwise be possible.

▸ Example: iodine in water or an aqueous solution of potassium iodide

or sodium iodide as the solvent , much larger amounts of iodine may
be dissolved in the second solvent as the result of the formation of a
water-soluble complex with the iodide salt.

▸ This reaction is taken advantage of, for example, in Iodine Topical

Solution, USP, prepared to contain about 2% iodine and 2.4% sodium
iodide.
▸ Many of the organic medicinal agents are either weak acids or weak bases, and
their solubility depends to a large measure on the pH of the solvent. These drugs
react either with strong acids or strong bases to form water soluble salts.

Examples
▸ The weak bases, including many of the alkaloids (atropine, codeine, and
morphine), antihistamines (diphenhydramine and promethazine), local
anesthetics (cocaine, procaine, and tetracaine), and other important drugs, are
not very water soluble, but they are soluble in dilute solutions of acids.

▸ Pharmaceutical manufacturers have prepared many acid salts of these organic

bases to enable the preparation of aqueous solutions , ex (diphenhydramine HCl)
, Atropine sulfate
▸ Organic medicinals that are weak acids include
the barbiturate drugs (e.g., phenobarbital ) and
the sulfonamides (e.g., sulfadiazine and
sulfacetamide).
▸ Phenobarbital sodium
▸ silver sulfadiazine
The rate of solution, that is, the speed at which the substance
dissolves, depends on:

▸ the particle size of the substance: the finer the powder, the greater the
surface area, which comes in contact with the solvent, and the more
rapid the dissolving process.

▸ the extent of agitation: the greater the agitation, the more unsaturated
solvent passes over the drug and the faster the formation of the
solution.
 SOLVENTS FOR LIQUID PREPARATIONS

▸ the selection of the proper solvent for a particular solute:

▸ solubility,
▸ clarity,
▸ low toxicity,
▸ viscosity,
▸ Compatibility with other formulative ingredients,
▸ Chemical inertness,
▸ palatability,
▸ odor, color,
▸ economy.
SOLVENTS FOR LIQUID PREPARATIONS
▸ PURIFIED WATER, USP, H2O
▸ Fixed oils
▸ ALCOHOL, USP
▸ DILUTED ALCOHOL, NF
▸ RUBBING ALCOHOL
▸ GLYCERIN, USP
▸ PROPYLENE GLYCOL, USP
 Methods of Preparation of Solutions

(a) Simple Solution

(b) Solution by Chemical Reaction
(c) Solution by Extraction
(a) Simple Solution
 Solutions of this type are prepared by dissolving the solute
in a suitable solvent (by stirring or heating).
 The solvent may contain other ingredients which stabilize or
solubilize the active ingredient.
(b) Solution by Chemical Reaction
These solutions are prepared by reacting two or more
solutes with each other in a suitable solvent e.g. Calcium
carbonate and lactic acid used to prepare Calcium lactate
mixture.

(c) Solution by Extraction

Plant or animal products are prepared by suitable
extraction process. Preparations of this type may be
classified as solutions but more often, are classified as
extractives. Extractives will be discussed separately.
 PREPARATION OF SOLUTIONS

▸ Most pharmaceutical solutions are unsaturated with solute.

▸ Thus, the amounts of solute to be dissolved are usually well

below the capacity of the volume of solvent employed.

▸ The strengths of pharmaceutical preparations are usually

expressed in terms of percent strength.
Some chemical agents in a given solvent require an
extended time to dissolve. To fasten dissolution, a
pharmacist may employ one of several techniques,
such as:
▸Applying heat,
▸Reducing the particle size of the solute,
▸Using a solubilizing agent,
▸Subjecting the ingredients to vigorous agitation.

Many medicinal agents are destroyed at elevated

temperatures and the advantage of rapid solution may
be completely offset by drug deterioration.
▸ If volatile solutes are to be dissolved or if the solvent is volatile
(as is alcohol), the heat would encourage the loss of these agents
to the atmosphere and must therefore be avoided.

▸ certain chemical agents, particularly calcium salts, undergo

exothermic reactions as they dissolve and give off heat.

▸ For such materials, the use of heat would actually discourage the
formation of a solution.

▸ a pharmacist may choose to decrease the particle size of the

solute.

▸ This may be accomplished by comminution (grinding a solid to a

fine state of subdivision) with a mortar and pestle on a small
scale or industrial micronizer on a larger scale.
Stability of solutions
Both physical and chemical stability of solutions
in their containers is very important
A solution must retain its clarity, colour, odour,
taste and viscosity over its shelf life.
▸ The formulation pharmacist must be wary of chemical interactions
between the various components of a solution that may alter the
preparation’s stability and/or potency.

▸ For instance, esters of p-hydroxybenzoic acid (methyl-, ethyl-,

propyl-, and butylparabens), frequently used preservatives in oral
preparations, have a tendency to partition into certain flavoring
oils .
▸ This partitioning effect could reduce the effective concentration of
the preservatives in the aqueous medium of a pharmaceutical
product below the level needed for preservative action.
 DRY MIXTURES FOR SOLUTION
▸ A number of medicinal agents, particularly certain antibiotics, e.g.,
penicillin V, have insufficient stability in aqueous solution to meet
extended shelf-life periods.

▸ Thus, commercial manufacturers of these products provide them

to the pharmacist in dry powder or granule form for reconstitution
with a prescribed amount of purified water immediately before
dispensing to the patient.

▸ The dry powder mixture contains all of the formulative

components, including drug, flavorant, colorant, buffers, and others,
except for the solvent.
▸ Once reconstituted by the pharmacist, the solution
remains stable when stored in the refrigerator for the
labeled period, usually 7 to 14 days

▸ This is a sufficient period for the patient to complete the

regimen usually prescribed.

▸ in case the medication remains after the patient

completes the course of therapy, the patient should be
instructed to discard the remaining portion, which
would be unfit for use at a later time.
 ORAL REHYDRATION SOLUTIONS
▸ Rapid fluid loss associated with diarrhea can
lead to dehydration accompanied by depletion
of sodium, potassium, and bicarbonate ions.

▸ Oral rehydration solutions are usually effective

in treatment of patients with mild volume
depletion, 5% to 10% of body weight. These are
available OTC
 SYRUPS

▸ Syrups are concentrated aqueous preparations

of a sugar or sugar substitute with or without
flavoring agents and medicinal substances.

• Antihistamine Syrup
• Acetaminophen Syrup
• Cough and Cold Syrup
 ELIXIRS

▸ Elixirs are clear, sweetened hydroalcoholic

solutions intended for oral use and are usually
flavored to enhance their palatability.

▸ Nonmedicated elixirs are employed as vehicles, and medicated

elixirs are used for the therapeutic effect of the medicinal
substances they contain.

▸ In addition to alcohol and water, other solvents, such as glycerin and

propylene glycol, are frequently employed in elixirs as adjunctive
solvents.
 ELIXIRS
▸ Phenobarbital Elixir
▸ Theophylline Elixir

▸ Medicated elixirs are formulated so that a

patient receives the usual adult dose of the drug
in a convenient measure of elixir. For most
elixirs, one or two teaspoonfuls (5 or 10 mL)
provide the usual adult dose of the drug.
 TINCTURES
▸ Tinctures are alcoholic or hydroalcoholic solutions prepared
from vegetable materials or from chemical substances.

▸ They vary in method of preparation, strength of the active

ingredient, alcoholic content, and intended use.

▸ When they are prepared from chemical substances (e.g.,

iodine, thimerosal), tinctures are prepared by simple
solution of the chemical agent in the solvent.
 TOPICAL SOLUTIONS AND TINCTURES
▸ The topical solutions employ an aqueous vehicle

▸ The topical tinctures employ an alcoholic vehicle.

▸ All medications intended for external use

should be clearly labeled for external use only.
36

Oral dosage forms:

1- Tablet:
▸ A tablet is a hard, compressed medication in round, oval or square
shape

The excipients include:

▸ Diluents - Provide bulkiness of tablet.
▸ Binders, glidants (flow aids) & lubricants to ensure efficient tableting.
▸ Disintegrants to ensure that the tablet breaks up in the digestive tract.
▸ Sweeteners or flavors to mask the taste of bad-tasting active
ingredients.
▸ Pigments to make uncoated tablets visually attractive.
37

Tablet
A coating may be applied to:
▸ hide the taste of the tablet's components.
▸ make the tablet smoother and easier to swallow.
▸ make it more resistant to the environment.
▸ extending its shelf life.
38

2-Buccal and Sublingual tablet:

▸ Sublingual & buccal medications are administered by placing them in
the mouth, either under the tongue (sublingual) or between the gum
and the cheek (buccal).

▸ The medications dissolve rapidly & are absorbed through the mucous
membranes of the mouth, where they enter into the bloodstream.

▸ Avoid the acid and enzymatic environment of the stomach & the drug
metabolizing enzymes of the liver.

▸ Examples of drugs administered by this route: e.g. vasodilators,

steroidal hormones.
39

3-Effervescent tablet:
▸ Effervescent tablets are uncoated tablets that generally contain acid
substances (citric and tartaric acids) and carbonates or
bicarbonates and which react rapidly in the presence of water by
releasing carbon dioxide.

▸ -They are intended to be dissolved or dispersed in water before use

providing:
▹ Very rapid tablet dispersion and dissolution.
▹ pleasant tasting carbonated drink.
40

4- Chewable tablet:
▸ They are tablets that chewed prior to swallowing.
▸ They are designed for administration to children
▹ e.g. vitamin products, Antacid tablets.
41
42
5- Capsule:
Solid unit dosage form that contain a solid, semi-solid, and liquid fill and a gelatin
shell.
▸ A capsule is a medication in a gelatin container.
Common excipients used in capsules are :
▹ Gelatin - Commonly used as gelling agent.
▹ Plasticizers - To ensure elasticity or mechanical stability.
▹ Additional Additives - Preservative, coloring and

Advantage: mask the unpleasant taste of its contents.

The two main types of capsules are:

▹ hard-shelled capsules, which are normally used for dry, powdered ingredients,
▹ soft-shelled capsules, primarily used for oils and for active ingredients that are
dissolved or suspended in oil.
43
44

6- Lozenge:
▸ It is a solid preparation consisting of sugar and gum, the latter giving
strength and cohesiveness to the lozenge and facilitating slow
release of the medicament.

▸ It is used to medicate the mouth and throat for the slow

administration of indigestion or cough remedies.
45

7- Pastilles:
▸ They are solid medicated preparations designed to dissolve slowly in
the mouth.

▸ They are softer than lozenges and their bases are either glycerol and
gelatin, or acacia and sugar.
46

8- Dental Cones:
▸ A tablet form intended to be placed in the empty socket following a
tooth extraction, for preventing the local multiplication of pathogenic
bacteria associated with tooth extractions.
▸ The cones may contain an antibiotic or antiseptic.
47

9-Pills
▸ Pills are oral dosage forms which consist of spherical masses
prepared from one or more medicaments incorporated with inert
excipients.
▸ Pills are now rarely used.
48

10- Granules:
▸ They are consisting of solid, dry aggregates of
Powder particles often supplied in single-dose
sachets.

▸ Some granules are placed on the tongue and

swallowed with water, others are intended to be
dissolved in water before taking.

▸ Effervescent granules evolve carbon dioxide when

added to water.
49

11- Powder (Oral):

▸ There are two kinds of powder intended for internal use.

▸ 1-Bulk Powders are multidose preparations consisting of solid, loose, dry

particles of varying degrees of fineness. They contain one or more active
ingredients, with or without excipients and, if necessary, coloring matter and
flavoring substances.
▸ - usually contain non-potent medicaments such as antacids since the patient
measures a dose by volume using a 5ml medicine spoon. The powder is then
usually dispersed in water or, in the case of effervescent powders, dissolved
before taking.

▸ 2-Divided Powders are single-dose presentations of powder ( for example, a

small sachet) that are intended to be issued to the patient as such, to be taken
in or with water.
50

12- Powders for mixtures:

▸ - The mixed powders may be stored in dry form and mixture prepared by the
pharmacist when required for dispensing , by suspending the powders in the
appropriate vehicle.
51

13-Liquid preparations:
▸ Oral solution:
Oral solutions are clear Liquid preparations for oral use containing one or
more active ingredients dissolved in a suitable vehicle.

▸ Oral emulsion:
Oral emulsions are stabilized oil-in-water dispersions, either or both phases
of which may contain dissolved solids.

▸ Oral suspension:
Oral suspensions are Liquid preparations for oral use containing one or more
active ingredients suspended in a suitable vehicle dispersed on shaking to
give a uniform suspension which remains sufficiently stable to enable the
correct dose to be - delivered.
52

13-Liquid preparations:
▸ Syrup:
It is a concentrated aqueous solution of a sugar, usually sucrose.
Flavored syrups are a convenient form of masking disagreeable tastes.

▸ Elixir:
-Itis pleasantly flavored clear liquid oral preparation of potent or nauseous
drugs.
- The vehicle may contain a high proportion of ethanol or sucrose together
with antimicrobial preservatives which confers the stability of the preparation.
53

13-Liquid preparations:
▸ Gargles:
They are aqueous solutions used in the prevention or treatment of throat
infections.
Usually they are prepared in a concentrated solution with directions for the
patient to dilute with warm water before use.

▸ Mouthwashes:
These are similar to gargles but are used for oral hygiene and to treat
infections of the mouth.
54