DIFFERENT DOSAGE

FORMS OF DRUGS 1 OF 5
LEARNING OUTCOMES:
1. List reasons for the incorporation of drugs into various dosage forms
2. Compare and contrast the advantages/disadvantages of various drug dosage
forms
3. Describe the information needed in pre-formulation studies to characterize a
drug substance for possible inclusion into a dosage form
4. Describe the mechanisms of drug degradation and provide examples of each
5. Describe the 5 types of drug instability of concern to the practicing
pharmacist
6. Describe the purpose and general protocol for accelerated stability studies
7. Summarize approaches employed to stabilize drugs in pharmaceutical dosage
forms.
INTRODUCTION TO DOSAGE FORMS
 Drug substances and crude drugs are very seldom used directly as medicines,
rather they are given as part of a formulation in combination wit one or more
non-medical agents that serve varied and specialized pharmaceutical
functions.
 The general area of study concerned with the formulation, manufacture,
stability, and effectiveness of pharmaceutical dosage forms is termed
pharmaceutics.
 The drug and pharmaceutical materials must be compatible with one another.
 The product should be manufactured with appropriate measures of quality
control and packaged in containers. It should be labeled to promote correct
use and be stored under conditions
PURPOSE OF DOSAGE FORMS:
 To provide the mechanism for the safe and convenient delivery of accurate
dosage.
 To protect the drug substance from the destructive influences of atmospheric
oxygen or humidity (coated tablets, sealed ampuls)
 To protect the drug substance from the destructive influence of gastric acid
after oral administration (enteric-coated labels)
 To conceal the bitter, salty, or offensive taster or odor of a drug substance
(capsules, coated tablets, flavored syrups)
 To provide liquid preparations of drug substances, either as dispersions
(suspensions) or as clear preparations (solutions)
 To provide rate-controlled drug action (various controlled-release tablets,
capsules, and suspensions)
 To provide optimal drug action from tropical administration sites
(ointments, creams, transdermal patches, and ophthalmic, ear, and nasal
preparations.
 To provide for insertion of a drug into one of the body’s orifices (rectal or
vaginal suppositories)
 To provide for placement of drugs directly in the bloodstream or body
tissues (injections)
 To provide for optimal drug action through inhalation therapy (inhalants
and inhalation aerosols)
APPLICATION OF DOSAGE FROMS
 The potent nature and low dosage of most of the drugs – Most drug
substances are administered in milligram quantities, meaning, it is much
too small to be weighed on anything but a sensitive prescription or
electronic analytical balance.
 When the dose of the drug is minute, as with ethynyl estradiol, solid
dosage forms such as tablets and capsules must be prepared with filler and
diluents so that the dosage unit is large enough to pick up with the
fingertips.
THINGS TO CONSIDER IN DOSAGE FORM DESIGN
1. Before formulating a drug substance into a dosage form, the desired
product type must be determined in so far as possible to establish the
framework for product development.
2. Then, various initial formulations of the product are developed and
examined for desired features and for pilot plant studies and production
scale-up.
3. The formulation that best meets the goals for the product is selected to be
its master formula.
4. Before a medicinal agent is formulated into one or more dosage forms,
among the factors considered are the physical and chemical properties of
the drug substance and various therapeutic considerations.
5. If the medication is intended for systematic use and oral administration
is desired, tablets/capsules are usually prepared because they are easily
handled by the patient and are most convenient in the self-administration of
medication. If a drug substance has application in an emergency in which the
patient may be comatose or unable to take oral medication, an injectable
form of the medication may also be prepared.
6. Many other examples of therapeutic situations affecting dosage from design
could be cited, including motion sickness, nausea, and vomiting, for which
tablets and skin patches are used for prevention and suppositories and
injections for treatment.
7. The age of the intended patient also pays a role in dosage form design. For
infants and children younger than 5 years of age, pharmaceutical liquids
rather than solid forms are preferred for oral administration.
8. These liquids, which are flavored aqueous solutions, syrups, or
suspensions, are usually administered directly into the infant’s or child’s
mouth by drop, spoon, or oral dispenser or incorporated into the child’s
food.
9. The palatability of some commercial products may not be acceptable to
some patients so different flavoring additives may be indicated to enhance
compliance; an example would be the FLAVOR X flavoring system.
10. A single liquid pediatric preparation may be use or infants and children
of all ages, with the dose of the drug varied by the volume administered.
In such instances, injections may be required. Infant-size rectal
suppositories may also be employed, although drug absorption from the
rectum is often erratic.
DRUG STABILITY: MECHANISM OF DEGRADATION, KINETICS AND
SHELF-LIFE
DO DRUGS UNDERGO DEGRADATION? – MECHANISMS OF DRUG
DEGRADATION
1. Hydrolysis is a solvolysis process in which (drug) molecules interact with
water molecules to yield breakdown products.
2. Oxidation is loss o electrons from an atom or a molecule.
3. Polymerization is a reaction between two or more identical molecules that
forms a new and generally larger molecule.
4. Chemical decarboxylation and deamination
 Decarboxylation- decomposition of organic acid and release of dioxide gas
 Deamination- removal of nitrogen-containing group from an organic amine.
DRUG AND DRUG PRODUCT STABILITY: KINETICS AND SHELF LIFE
 Stability- the extent to which a product retains within specified limits and
throughout its period of storage and use (i.e., its shelf life) the same properties
and characteristics tat is possessed at the time of its manufacture.
 Five types of stability:
 Chemical: Each active ingredient retains its chemical integrity and labeled
potency within the specified limits.
 Physical: The original physical properties, including appearance, palatability,
uniformity, dissolution, and suspendability, are retained.
 Microbiologic: Sterility or resistance to microbial growth is retained according
to the specified requirements. Antimicrobial agents retain effectiveness within
the specified limits.
 Therapeutic: The therapeutic effect remains unchanged.
 Toxicologic: No significant increase in toxicity occurs.
 Stability and expiration dating are based on reaction kinetics, that is, the
study of the rate of chemical change and the way this rate is influenced by
concentration of reactants, products, and other chemical species and by
factors such as solvent, pressure, and temperature.
ROUTES OF ADMINISTRATION
 Routes of administration is a path by which a drug, fluid or other substance
is taken into the body.
 Local effects- achieved by direct application of the drug to the desired site
of action, such as the eye, nose, or skin.
 Systematic effects- result from the entrance of the drug into the circulatory
system and transport to the cellular site of its action.
 An individual drug substance may be formulated into multiple dosage from
that result in different drug absorption rates and times onset, peak, and
duration of action.
 Routes of Administration Intramuscular Muscle
Term Site Epicutaneous (topical) Skin surface
Oral Mouth Transdermal Skin surface
Personal Gastrointestinal Tract
via mouth Conunctival Conjunctiva
Sublingual Under the tongue Intraocular Eye
Parenteral Other than the Intranasal Nose
gastrointestinal tract (by
injection) Aural Ear
Intravenous Vein Intra-respiratory Lung
Intra-arterial Artery Rectal Rectum
Intracardiac Heart Vaginal Vagina
Intraspinal or Intrathecal Spine
Intraosseous Bone
Intra-articular Joint
Intrasynovial Joint fluid area
Intracutaneous, Intradermal Skin
Subcutaneous Beneath the skin
Solutions Syrups, Elixirs
Suspensions Magmas
Gels, Powders
Sublingual Tablets,
Troches, Iozenges Drops
(solutions)
Parenteral Solutions
Suspensions
Epicutaneuous, Ointments, Gel Creams,
Transdermal (topical Infusion pumps, Pastes
Plasters, Powders Aerosols,
Lotions
Transdermal patches, disks solutions
Intra-respiratory Aerosols
Conjunctival Contact lens inserts
Ointments
Intraocular Solutions
Intranasal Solutions, Sprays
Inhalants, Ointments
Intra-aural Suspensions
Intra-respiratory Aerosols
Rectal Solutions Ointments
Suppositories, Gels
Vaginal Solutions, Ointments
Emulsion, foams, Gels
Tablets
Inserts, suppositories, sponge
Urethral Solutions Suppositories
 CLASSIFICATION OF DOSAGE FORMS
SOLID DOSAGE FORMS AND SOLID • Powder and Granules
MODIFIED RELEASE DRUG DELIVERY • Capsules
SYSTEMS • Tablets
• Solid Oral Modified-Release Dosage Form and
Drug Delivery Systems
SEMI-SOLID DOSAGE FORMS AND • Ointments
TRANSDERMAL SYSTEM • Creams
• Gels
• Transdermal Drug Delivery Systems
• Suppositories, Inserts & Sticks
LIQUID DOSAGE FORMS • Solutions
o Syrup, Elixir, Tinctures
• Dispersed Systems
o Suspensions, Gels, Magma and Aerosols
STERILE DOSAGE FORMS AND DELIVERY • Parentals
SYSTEMS • Biologics
• Special Solutions and Suspensions
NOVEL AND ADVANCED DOSAGE FORMS, • Radiopharmaceuticals
DELIVERY SYSTEMS AND DEVICES • Products of Biotechnology
• Novel Dosage Forms and Drug Delivery
Technology
A. SOLID DOSAGE FORMS AND SOLID MODIFIED-RELEASE DRUG
DELIVERY SYSTEMS
a. POWDER AND GRANULES
• The term “powder” has more than one connotation in pharmacy.
• It may be used to describe a type of pharmaceutical preparation, that is, a medicated
powder intended for internal (i.e., oral powder) or external (i.e., topical powder) use.
• A powder is defined as a dosage form from composed of a solid or mixture of solids
reduced to a finely divided state and intended for internal or external use.
Advantages: Disadvantages:
 Flexibility in computing - Not easily welted
 Relatively dry & devoid of moisture - Inaccuracy of the dose
 Relatively stable - not suitable for dispensing
- Some powders are
hygroscopic & deliquescent
Micromeritics
 The science and technology of small particles. Knowledge and control of
particle size and the size range of particles are significant importance in
pharmacy because the size and surface area of a particle is related to the
physical, chemical and pharmacologic properties of a drug.
 Particle size- is a notion introduced for comparing dimensions o solid
particles, liquid particles, or gaseous particles.
 Angle of Repose- a technique for estimating the flow properties of a
powder.
 Porosity- AKA void fraction, is a measure of a void spaces in material and
is a fraction of the volume of voids over the total volume, between 0 and 1,
or as a percentage between 0% and 100%
 Particle Size Analysis
 Used to obtain quantitative data regarding the size, shape & distribution of drug particles &
other components to be used in the formulation.
Standards for Vegetable and Animal Drugs Standards for Chemical Drugs

Descriptive Sieve Limit Descriptive Sieve Limit

Term Size Term Size
Very Coarse No. 8 NMT 20% pass Coarse No. 20 NMT 60% pass
through No. 60 through No. 40
Coarse No. 20 NMT 40% pass
through No. 60 Moderately No. 40 NMT 60% pass
Moderately No. 40 NMT 40% pass Coarse through No. 40
Coarse through No. 80
Fine No. 60 NMT 40% pass Fine No. 60 No limit to greater
through No. 100 Very fine No. 120 fineness
Very Fine No. 80 No limit to greater
fineness
 Particle size can influence the following factors:
 Dissolution rate of particles intended to dissolve
 Suspendability of particles intended to remain undissolved but uniformly
dispersed in a liquid vehicle
 Uniform distribution of a drug substance
 Penetrability of particles intended to be inhaled for deposition deep in the
respiratory tract.
 Lack of grittiness of solid particles in dermal ointments, creams, and
opthaimic preparations
TYPES OF POWDERS
I. BULK POWDERS
• Oral powders generally supplied as finely divided powder or as effervescent
granules.
• Dentrifices may be prepared in the form of bulk powder generally containing
soap or detergent, mild, adhesive, and anticariogenic agent.
• Insufflations are finally divided powders introduced into body cavities such as
the ears, nose, throat, tooth sockets and vagina with the use of an insufflator
(powder blower)
• Triturations are dilutions of potent powdered drugs prepared by intimately
mixing them with a suitable diluent in 1:10 dilutions.
• Dusting powders are locally applied non-toxic preparations that are intended to
have no systematic action.
• Aerosols are often administered with the aid of inhalers, without delivers
micronized drugs in metered quantities.
• Douche powders are soluble powders intended to be dissolved in water prior to use
as antiseptic or cleaning agents for a body cavity.
II. DIVIDED POWDERS
 Divided powders or “chartulae”; known as individualize powders, paper tablets,
“papelitos”.
 Types of Papers in Paper Tablets.
• Simple Bond Paper- has no moisture resistance
• Vegetable Parchment- a thin semi-opaque with limited moisture resistance
• Glassine- a glazed, transparent paper, also with limited moisture resistance
• Waxes Paper- a transparent waterproof paper: used for hygroscopic or deliquescent
powder
GRANULES
 Granules are dosage form composed of dry aggregates of powder particles that
may contain one or more APIs, or without other ingredients.
 Granulation- process used to prevent segregation of powders to improve
compressibility.
Advantages of Granules:
 Flows well compared to powders
 Facilitates the transport of the drug material from the hopper to the tablet press.
 Less surface area – more stable from atmosphere humidity – less tendency to
cake or harden.
 Easily Wetted – suitable for material that needs reconstitution prior to use.
 Effervescent Granulated Salts
• Effervescent dosage forms are tablets or granules, contains ingredients that,
when in contact wit water, rapidly release carbon dioxide.
• Effervescent salts are granules or coarse to very coarse powders containing a
medicinal agent in a dry mixture usually composed of sodium bicarbonate,
citric acid, and tartaric acid.
• Problems:
 When Tartaric acid is use as the sole acid in effervescent granules, the resulting
granules will lose their firmness & crumble.
 When Citric Acid is used as the sole acid in effervescent granules. The resulting
granules will be sticky and difficult to granulate.