BASIC PRINCIPLE OF PHARMACEUTICAL DOSAGE

FORMPHARMACEUTICS DEPARTMENT

PHARMACY STUDY PROGRAM FACULTY OF MEDICINE

BRAWIJAYA UNIVERSITY

OUTLINE

DRUG RESEARCH & DEVELOPMENT

VARIOUS PHARMACEUTICAL DOSAGE FORM

CONSIDERATIONS OF PHARMACEUTICS, BIOPHARMACEUTICAL & PHARMACOKINETICS IN

DESIGNING DOSAGE FORM

DIGOXIN

1785

HISTORY OF DRUGS

CALCITONIN

HISTORY OF DRUGS

THE PROCESS OF DRUG DISCOVERY

AND DEVELOPMENTIS COMPLEX.

Chemical & physical

Toxicologic

Metabolic degradation

Pharmacokinetic

Mechanism of action

PHARMACEUTICS

THE PROPER DESIGN AND FORMULATION OF A DOSAGE FORM REQUIRES CONSIDERATION OF

THE PHYSICAL, CHEMICAL, AND BIOLOGIC CHARACTERISTICS

THE DRUG AND PHARMACEUTICAL MATERIALS MUST BE COMPATIBLE

DRUG PRODUCT THAT IS STABLE, EFFICACIOUS, ATTRACTIVE, EASY TO ADMINISTER, AND SAFE.

The general area of study concerned with the formulation,

manufacture, stability, and effectiveness of pharmaceutical

dosage forms

PHARMACEUTICAL DOSAGE FORM

Routes of administration

OralTable, Capsule,

Solution, Emulsion, Suspension

Rectal Suppositories

Parenteral Injection

TopicalOintments, Gel,

CreamOther routes : nasal, otic, opthalmic, etc

Choose the route......

ROUTES OFDRUG ADMINISTRATION

ROUTE OF ADMINISTRATIONAND DELIVERY SYSTEM OF PRIMARY

DOSAGE FORMS

CONSIDERATION OF CHOSING THE ROUTE

NEONATES, CHILDREN, ADULTS, GERIATRICS,

WEIGHTS

STATES OF ILLNESS

It has been said that the only difference between a drug and a poison is the dose

PRODUCT OF APPLICATION OF THE PHARMACEUTICAL SCIENCES

Design

Use

Production

Development PHARMACEUTICAL FORMULATION

Active Therapeutic Ingredients

Nontherapeutic/pharmaceutical ingredients

Filler, thickener, solven, suspending agent Penetration enhancer, flavor, colorants, sweetener

THE NEED FOR DOSAGE FORMS

Coated tablet Sealed ampuls

Protect from the destructive influences

Capsule, coated tablet Flavoured syrup

Conceal the bitter, salty or offensive taste/odor

suspensionsLiquid preparations of

substances insoluble/unstable in the desired vehicle

Syrups, solutionsProvide clear liquid dosage forms

Rectal Vaginal suppositories

Provide for insertion of a drug into one of the

bodys orifice

Injections

Drugs directly in the bloodtream or body

tissues

inhalants & inhalation aerosols Topical : ointment, cream, patch Ophtalmic, ear, nasal

Optimal drug action to the certain sites

various controlled-release tablets, capsules, and suspensionsProvide rate-controlled

drug action

GENERAL CONSIDERATIONSIN DOSAGE FORM DESIGN

DETERMINE THE DESIRED PRODUCT TYPE

DRUG RELEASE PROFILE, BIOAVAILABILITY, CLINICAL EFFECTIVENESS

THE MANNER IN WHICH IT IS TREATED (LOCALLY OR THROUGH SYSTEMIC)

THE AGE

THERAPEUTIC SITUATIONS

PHARMACEUTICS CONSIDERATIONS

PREFORMULATION STUDIES

PHYSICAL DESCRIPTION

MICROSCOPIC EXAMINATION

HEAT OF VAPORIZATION AEROSOL DOSAGE FORMS

MELTING POINT DEPRESSION PURITY

THE PHASE RULE

PARTICLE SIZE

POLYMORPHISM

SOLUBILITY

PHYSICAL DESCRIPTION

SOLID MATERIALS, CRYSTALLINE OR AMORPHOUS CONSTITUTION.

THE PURITY IDENTIFICATION AND FOR EVALUATION OF ITS CHEMICAL, PHYSICAL, AND BIOLOGIC

PROPERTIES.

CHEMICAL PROPERTIES : STRUCTURE, FORM, AND REACTIVITY.

PHYSICAL PROPERTIES : PHYSICAL DESCRIPTION, PARTICLE SIZE, CRYSTALLINE, STRUCTURE, MELTING

POINT, AND SOLUBILITY

VOLATILITY

STABILITY

MICROSCOPIC EXAMINATION

IT GIVES AN INDICATION OF PARTICLE SIZE AND SIZE RANGE OF THE RAW MATERIAL ALONG

WITH THE CRYSTAL STRUCTURE.

SOLID DRUG POWDERS : SPHERICAL AND OVAL POWDERS FLOW MORE EASILY THAN NEEDLE-

SHAPED POWDERS AND MAKE PROCESSING EASIER

THE PHASE RULE

PROVIDE A VISUAL PICTURE OF THE EXISTENCE AND EXTENT OF THE PRESENCE OF SOLID AND

LIQUID PHASES IN BINARY, TERNARY, AND OTHER MIXTURES

I Solid A + solid B

II Solid A + melt

III Solid B + melt

IV Melt

PARTICLE SIZE

AFFECTS :

DISSOLUTION RATE, BIOAVAILABILITY, CONTENT UNIFORMITY, TASTE, TEXTURE, COLOR, AND

STABILITY

FLOW CHARACTERISTICS AND SEDIMENTATION RATES

PARTICLE SIZE SIGNIFICANTLY INFLUENCES THE ORAL ABSORPTION PROFI LES OF CERTAIN

DRUGS, INCLUDING GRISEOFULVIN, NITROFURANTOIN, SPIRONOLACTONE, AND PROCAINE

PENICILLIN

POLYMORPHISM

DIFFERENT PHYSICOCHEMICAL PROPERTIES, INCLUDING MELTING POINT AND SOLUBILITY

AMORPHOUS FORM OF A COMPOUND IS ALWAYS MORE SOLUBLE THAN A CORRESPONDING

CRYSTAL FORM

SOLUBILITY

DRUG MUST POSSESS SOME AQUEOUS SOLUBILITY FOR THERAPEUTIC EFFICACY

EXERT A THERAPEUTIC EFFECT, IT MUST FIRST BE IN SOLUTION.

MODIFI CATION OF THE DRUG INTO SALT OR ESTER FORMS IS FREQUENTLY USED TO INCREASE

SOLUBILITY.

ADJUSTMENT OF THE PH OF THE SOLVENT TO ENHANCE SOLUBILITY

IT IS DESIRABLE TO USE COSOLVENTS OR OTHER TECHNIQUES SUCH AS COMPLEXATION,

MICRONIZATION, OR SOLID DISPERSION TO IMPROVE AQUAEOUS SOLUBILITY

DOSAGE FORM DESIGN: BIOPHARMACEUTICAL & PHARMACOKINETIC CONSIDERATIONS

BIOPHARMACEUTICS

The area of study embracing this relationship

between the physical, chemical, and biologic

sciences as they apply to drugs, dosage

forms, and drug action

PHARMACOKINETICS The area of study that elucidates the time course of drug concentration in the blood and tissues. It

is the study of the kinetics of absorption,

distribution metabolism, and excretion (ADME) of

drugs and their corresponding pharmacologic,

therapeutic, or toxic effects in animals and man.

ABSORPTION

DOSAGE AND KINETICS OF NITROGLYCERIN IN VARIOUS DOSAGE FORMS

CRYSTAL OR AMORPHOUSDRUG FORM

NOVOBIOCIN AND CHLORAMPHENICOL PALMITATE, ARE ESSENTIALLY INACTIVE WHEN

ADMINISTERED IN CRYSTALLINE FORM, BUT WHEN THEY ARE ADMINISTERED IN THE

AMORPHOUS FORM, ABSORPTION FROM THE GASTROINTESTINAL TRACT PROCEEDS RAPIDLY,

WITH GOOD THERAPEUTIC RESPONSE

THE CRYSTALLINE FORMS OF PENICILLIN G AS THE POTASSIUM SALT OR SODIUM SALT ARE

CONSIDERABLY MORE STABLE THAN THE ANALOGOUS AMORPHOUS FORMS

SALT FORMS

THE ADDITION OF THE ETHYLENEDIAMINE MOIETY TO THEOPHYLLINE INCREASES THE WATER

SOLUBILITY OF THEOPHYLLINE FIVEFOLD

DIMINISHED THE NEED TO USE HYDROALCOHOLIC MIXTURES SUCH AS ELIXIRS

SOME FACTORS THATINFLUENCE BIOAVAILABILITY

OF ORAL DRUGS

DRUG STANDARDS

AS THE SCIENTIFIC BASIS FOR DRUGS AND DRUG PRODUCTS DEVELOPED, SO DID THE NEED

FOR UNIFORM STANDARDS TO ENSURE QUALITY.

MONOGRAPHS AND REFERENCE BOOKS CONTAINING SUCH STANDARDS TO BE USED BY

THOSE INVOLVED IN THE PRODUCTION OF DRUGS AND PHARMACEUTICAL PRODUCTS.

ORGANIZED SETS OF MONOGRAPHS OR BOOKS OF THESE STANDARDS ARE CALLED

PHARMACOPEIAS OR FORMULARIES.

THE UNITED STATES PHARMACOPEIA AND THE NATIONAL FORMULARY

HANDBOOK OF PHARMACEUTICAL EXCIPIENTS (HOPE)

ALL ABOUT EXCIPIENTS

CONCENTRATION, STABILITY, COMPATIBILITY, INTERACTIONS, SOLUBILITY

Any Question?