Professional Documents
Culture Documents
Dosage Chapter 6
Dosage Chapter 6
Intimate mixtures of dry, finely divided drugs and/or Contain one or more active ingredients with or
chemicals used externally or internally without other ingredients
Dusted on the affected area from sifter-type Particles of pharmaceutical powders range from:
container or applied from powder aerosol
Extremely coarse: about 10 mm to 1 cm in
Should bear a label marked external use only diameter
Solid Materials Extremely fine: approaching colloidal
dimensions of 1 micron or less
Characterized to determine their chemical and physical
features before the preparation of pharmaceutical Micromeritics
products including:
Science of small particles
Morphology, purity, solubility, stability,
particle size, uniformity, compatibility with Characteristics included: particle size, angle of
any other formulation components repose, bulk volume, size distribution,
porosity, apparent density, shape, true volume,
For efficient production of a finished dosage form: bulkiness
optimum therapeutic efficacy, adjustment and control of
powder’s particle size USP Standings for Powders of Animals and Vegetable Drugs
For pharmaceutical testing and measurement, Very Coarse (No. 8) 8 Not more than
reduction of particle size of powders (nmt) 20% through
1
a no.60 sieve Methods for the Determination of Particle Size
Coarse (No.20) 20 Nmt 40% through a Light energy diffraction or light scattering
no.80 sieve
Reduction in light reaching the sensor as the
Moderately Coarse 40 Nmt 40% through a particle dispersed in a liquid or gas, passes
(No.40) no.80 sieve through the sensing zone
To obtain quantitative data of drug and other components Range: 1.4 to 100 micrometers
used in pharmaceutical formulations on the size,
distribution, and shape Cascade impaction
Variety of Important Factors Particle Size can Influence Principle: a particle driven by an air stream
will heat a surface in its path but its inertia is
Dissolution rate of particles sufficient to overcome the drag force that tends
to keep it in the airstream
Intended to dissolve
Particles separated into various size ranges by
Drug micronization increases rate of drug increasing the velocity of the airstream
dissolution and its bioavailability
Driven by an airstream will hit a surface in its
Suspendability of particles path, provided that its inertia is sufficient to
overcome the drag force that tends to keep in
Intended to remain undissolved but uniformly the airstreams
dispersed in liquid vehicle
A single method may be sufficient.
Example: fine dispersions have particles
approximately 0.5 to 10 um Combination of methods preferred for certainty of size
and shape parameters
Uniform distribution of a drug substance in a powder
mixture or solid dosage form Particle reduction points out: a decrease in particle size
will result in an increase in the number of particles and
To ensure dose to dose content uniformity total surface area (inversely proportional)
Penetrability of particles
Example: 1 to 5 um
2
Separate fine particles from coarse by grinding Ensure the uniform distribution of
in water the potent drug
Indicated when the potent and other
Reducing particle size forming a paste of the ingredients are:
solid with a minimum amount of a levigating o Same color
agent and then triturating the paste in a mortar o Visible sign of mixing is
or on slab with a spatula lacking
Examples: strychnine sulfate, arsenic, mercury
Small-scale preparation of ointments bichloride, atropine in convenient
concentration using lactose as the diluents for
Reduce the particle size and grittiness of added use at the Rx counter
powders Sifting
Powders mixed by passing through the sifters:
Mortar and pestle or ointment tile is used. results in light, fluffy product
Not acceptable for incorporation of potent
Trituration and levigating agent: insoluble drugs into a diluent powder
powder (mineral oil and glycerine)
Tumbling (rotating chamber)
Use of machine or motorized equipment for
The basis of choice of levigating agent:
industrial purposes
Time consuming
Ability to form a smooth paste with
Small scale preparations: spatulation,
the substance
trituration, sifting
Twin Shell Blender
Compatibility with the product
Mixes solid particles
*** Water cannot be used for Blending of Powders
levigating a substance for oleaginous The “V” blender: an efficient and versatile blending
ointment base. machine for mixing and lubrication process of dry
powders homogeneously
Comminution of Drugs on a Large-Scale The ribbon blender: an efficient and versatile blending
machine for mixing dry granules and powders
Various types of mills and pulverizers homogeneously
Routes in Administering Medicated Powders
Example: FitzMill Comminutor For internal use:
Taken orally after mixing with water
Used for particle reduction with For constitution with a liquid solvent or vehicle
attached containment system for Some inhaled for local and systemic effects
protection of environment and Others as injection
prevention of product combination Others as vaginal douche
For external use:
Collection or containment system: Dusted on the affected area (sifter-type
container) or applied from powder aerosol
Protects the environment form chemical dust Should bear a label marked external use only
or a similar label
Reduces product loss
3
Administered by inhalation with the aid of dry-powder Forms rectangular or
inhalers square block of powder
Deliver micronized particles of medication in metered Having uniform depth
quantities 1um to 6um range in diameter Each block transferred to a powder
Treatment of asthma and other bronchial disorders paper and wrapped
Contain inert propellants and pharmaceutical diluents Geometric dilution method
such as crystalline alpha-lactose monohydrate Powders properly blended
To aid the formulation’s flow properties and Small amount of potent substances
metering uniformity mixed with large amount of diluents
To protect the powder from humidity Ensures uniform distribution of the
Mechanical devices used: pressurized aerosols, spinhaler potent drug (same color with other
(cromolyn Na from capsules), blowers or insufflators ingredients and visible sign of
Powders to various parts of the body after mixing is lacking)
depression of rubber bulb causing turbulence in No powder in the folds, and should not
the vessel forcing the powder out through the escape with moderate agitation
orifice in the tip Label placed on the container or affix a
Insufflator label of directions to each paper
Powder is placed in the vessel. Cellophane or plastic envelopes (moisture
resistant resulting in uniform packaging)
When the rubber bulb is depressed, internal turbulence
To enclose individual doses or units
disperses the powder and forces it from orifice.
Used than folded individual powder
Insufflations
papers
Finely divided powders introduced into the body cavities
Advantages of divided powders:
such as the ears, nose, throat, tooth sockets and vagina
Flexibility
Examples: Rapid therapeutic effect
Norisodrine Sulfate Aerohaler Cartridge Stability
(Abbott): specialized equipment or inhalation Ease of administration
Cromolyn Sodium Powder: relieve bronchial Disadvantages of divided powders:
asthma Time consuming to prepare
Types of Powders Not well suited for dispensing of
Bulk powders many unpleasant tasting hygroscopic
Dispensing powder medication in bulk drug
quantities (nonpotent substances) Inaccuracy
Bulk powders available in prepackaged
amounts:
Anatacids (ex. sodium bicarbonate)
and laxatives (ex. Psyllium:
Metamucil)
o Taken by mixing with water or
other beverage before
swallowing Papers that may be used
Douche powders (ex. Massengil Simple bond paper: opaque paper
Powder): dissolved in warm water by with no moisture resistant properties
the patient for vaginal use Vegetable parchment: opaque
Mediacated topical anti-infectives: moisture resistant
for external application to the skin Glassine: glazed transparent moisture
(ex. bacitracin zinc and polymyxin B resistant
sulfate) or antifungals (ex. tolnaftate) Waxed paper: transparent waterproof
Non-medicated: Brewer’s yeast paper
powder containing B-complex Powders containing:
vitamins and other nutritional Hygroscopic and deliquescent
supplements materials: waterproof or waxed paper
Divided Powders Limited barrier against moisture is
Form of individual dosing units (block necessary: glassine and vegetable
and divide method) parchment papers
Dispensed in chartulae (folded papers), Volatile components: waxed or
metal foil, small heat-sealed or resealable glassine papers
plastic bags Neither volatile nor ingredients
Based on the amount to be taken or used adversely affected by air moisture:
at a single time white bond paper
Examples: headache powders, powdered Examples of finely divided powders:
laxatives, and douche powders Oral powders: supplied as finely as
Properly blended using the geometric divided powders or effervescent
dilution method for potent substances granules
Block and divide method Douche powders: generally dissolved
For nonpotent powders in warm water for vaginal use
Entire amount of prepared powder on Medicated or non-medicated
a pill tile powders: for external application
o With a large spatula divided usually dispensed in sifter cans for
into equal amounts convenient application the skin
4
Dentifrices or dental cleansing Official powders for topical use:
powders Absorbable Dusting Powder: gloves lubricants
Denture powders: for dentifrices or Compound Iodochlorohydroxyquin Powder, NF:
foe adhesive to hold dentures vaginal insufflations as antimicrobial
Methylbenzenthonium Chloride Powders, NF: local
Douche Powders anti-infectives for diaper rash in infants
Products completely soluble and are intended to be Granules
dissolved in water prior to use as antiseptic or cleansing Prepared aggromalates of smaller particles of powder
agent for body cavity Irregularly shaped but may be spherical
Components: 4-12 sieve size range, although granules of various mesh
Boric acid or borax sizes may be prepared depending upon their application
Astringents as K alum, ammonium alum, Provide a pleasant vehicle for selected drug products
ZnSO4 with bitter, salty taste
Antimicrobial as oxyquinoline sulfate or Prepared by: wet method, dry method
povidone iodine Examples:
Quaternary ammonium compounds as Pricipen (ampicillin): for oral suspension (for
benzethonium chloride reconstitution)
Detergents as sodium lauryl sulfate Senokot granules: for laxative
Oxidizing agents as sodium perborate Effervescent products as Bromo Seltzer
Salts as sodium citrate, sodium chloride K-Lyte: granulations of effervescent products
Aromatic as menthol, thymol, eucalyptol, compressed into tablet
methyl salicylate and phenol
Packaging: may be in a wide mouth glass jar to protect
from volatile constituents and by bulk powder boxes
Dentifrices
5
Milling equipment: used to improve
flow, reduce segregation, enhance
drying, and limit wide particle size
distribution
Characteristics of granules which are advantageous over
powders:
Flow well
More stable to atmospheric humidity
Less likely to cake or harden upon standing
Easily wetted by liquids
Effervescent granulated salts
Granules or coarse to very course powders
containing a medicinal agent in a dry mixture
Composition: sodium bicarbonate, citric acid,
tartaric acid
If water is added: effervescence
If tartaric only: loose firm
If citric only: pasty
Pleasant vehicle to mask of bitter and salty
tastes
Example: sodium phosphate: cathartic
Two methods of preparation:
Dry method or fusion method:
binding agent for the powder
mixture: one molecule or water
present in each molecule of citric
acid
Wet method: binding agent: water
added to alcohol as the moistening
agent not the water of crystallization
from the citric acid: forming the
pliable mass for granulation
o Examples: Zantac
Efferdose tablets
o Lactinex granules: mixed
culture of Lactobacillus
acidophilus and
Lactobacillus bulgaricus in
1g packets
o Treatment of
uncomplicated diarrhea,
usually mixed with water,
beverages, sprinkled on
food or eaten plain
Dry and wet methods:
Objectives of using the method:
o To determine the proper
formula for the preparation
that will result in effective
effervescent and effect of
the product
o Efficient use of the acids
and base present
o Stable granulation
o Pleasant taste