FORMULATION AND DEVELOPMENT

DOSAGE FORM CONSIDERATIONS

SCHEDULE Y APPENDIX-I

Data to be submitted along

with the application to conduct clinical trials /import/manufacture of new drug for marketing in the country .

1. Introduction2. Chemical and pharmaceutical

information2.1 Information on active

ingredients Drug information (Generic name,Chemical

name or INN)2.2 Physicochemical dataa. Chemical name and structure

Empirical formula Molecular weight

b. Physical properties Description Solubility Rotation Partition coefficient Dissociation constant

2.3 Analytical data Elemental analysis Mass spectrum NMR spectrum IR spectra UV spectra Polymorphic identification

2.4 Complete monographic Specification include

Identification Identity/quantification of impurities Enantiomeric purity Assay

2.5 Validations Assay method Impurity estimation method Residual solvent/other volatile

impurities

2.6 Stability studies(addnl details in app IX) Final release specification Reference standard

characterization Material safety data sheet

2.7 Data on formulation Dosage form Composition Master manufacturing formula Details of the

formulation(including active ingredients)

In process control check Finished product specification Excipient compatibility study Validation of the analytical

method

Comparative evaluation with international brand(s) or approved indian brands, If applicable Pack presentation Dissolution Assay Impurities Content uniformity pH

Force degradation studyStability evaluation in market intended pack at proposed storage conditionsPacking specificationsProcess validation

WHAT IS FORMULATION?

The conversion of a drug in to dosage form using suitable pharmaceutical ingredients and excipients.

NEED FOR DOSAGE FORM

ACCURATE DOSAGE

COATED TABLETS AND SEALED AMPULES

ACID RESISTANT

CONCEAL TASTE

INSOLUBLE AND UNSTABLE SUBSTANCES IN SUITABLE VEHICLE (SUSPENSIONS)

CLEAR LIQUID DOSAGE FORMS(SYRUPS)

RATE CONTROLLED

TOPICAL APPLICATIONS

INSERT DRUG IN TO ONE OF THE BODY ORIFICES(SUPPOSITORIES)

PLACEMENT OF DRUG DIRECTLY IN TO BODY FLUIDS(INJECTIONS)

INHALATIONS THERAPY

GENERAL CONSIDERATIONS

DRUG RELEASE PROFILEBIOAVAILABILITYCLINICAL EFFECTIVENESSTHERAPEUTIC CONSIDERATIONS NATURE OF ILLNESS MANNER IN WHICH IT IS TREATED AGE ANTICIPATED CONDITION OF THE

PATIENT

DIFFERENT TYPES LIQUID DOSAGE FORMS SOLUTIONS

ORAL SOLUTIONS SYRUPS ELIXIRS

PARENTERALS SUSPENSIONS EMULSIONS

The drug molecule is dissolved or suspended in the liquid vehicle

SOLID DOSAGE FORMS

POWDERSTABLETS SUSTAINED RELEASE ENTERIC COATED

CAPSULES HARD GELATIN SOFT GELATIN

SEMISOLID DOSAGE FORMS

OINTMENTSSUPPOSITORIESPESSARIESCREAMS

INHALATIONS

AEROSOLS

CONSTITUENTS OF A DOSAGE FORM

DRUGVEHICLEPHARMACEUTICAL INGREDIENTS AND EXCIPIENTS

DRUG

DATA FROM PREFORMULATION STUDIES

eg:solubility data stability data etc.

PHARMACEUTICAL INGREDIENTS ANDEXCIPIENTS

Produce drug in to final dosage formSolutions Solvents to dissolve the drug

substances Flavors and sweeteners Colorants Preservatives Stabilizers

TABLETS

Diluents and fillers Binders Antiadherents or lubricants Disintegrating agents Coatings Semisolid dosage forms

SEMISOLID DOSAGE FORMS

Pharmaceutical bases

Monograph of pharmaceutical excipients

Non propreitary,chemical,commercial names Empirical and chemical formulaePharmaceutical specificationsChemical and physical propertiesIncompatibilitiesInteractions with other excipients and drug substancesRegulatory statusApplication in pharmaceutical formulation or technology

HARMONIZATION OF STANDARDS

As per four Pharmacopeias U.S.P – N.F B.P European Pharmacopeia Japaneese Pharmacopeia

PALATABILITY

Liquids by oral routeMask the disagreeable tasteCapsule or coated tabletsChewable tablets to be sweetened and flavoredPrediction of taste characteristics of a new drug is speculative

SELECTION OF FLAVORING AGENT

Taste of drug substance itself

Cocoa flavored vehicles – mask bitter taste

Cinnamon,orange,raspberry and other flavors – salty drugs more palatable

FACTORS IN SELECTION

AGE Children – sweet candy like

preparations with fruity flavours Adults –less sweet prepns

FLAVORS CONSIST OF Oil or water soluble liquids and dry

powders

Oil soluble carriers – soyabean and other edible oils

Water soluble carriers- water, ethanol , propylene glycol, glycerine and emulsifiers

Dry carriers include – maltodextrins, cornsyrup solids,modified starches , gumarabic , salts,sugars and whey protein.

Flavors degrade by exposure to Light Head space oxygen Temperature Water Enzymes

Types of flavor : According to code of Federal regulations under Food Drug and Cosmetics Act Natural Artificial Spice

COLOURING AGENTS

USED FOR ESTHETIC ENHANCEMENTTYPES INHERENT eg:

Sulfur(yellow),riboflavin(yellow),cupric sulfate(blue),ferrous sulfate(red).

AGENTS USED AS COULOURANTS synthetic and natural

Mineral source : eg: Zinc oxide is used to impart

pink color to calamine Derivatives of aniline

REGULATIONS FOR USE

Food and Drug Act in 1906 : Few colorants certified or permitted.

Federal Food ,Drug and Cosmetics Act of 1938 as amended in 1960 .

Certified colours classified based upon their use FD&C color additives

D&C color additives

External D&C color additives

TOXICITY STUDIES

Study protocol usually call 2 year studyLong term toxicity and carcinogenicityFive categories : Clear evidence of carcinogenic activity Some evidence Equivocal evidence indicating uncertainty No evidence Inadequate study for studies

CERTIFICATION STATUS

CONTINUALLY REVIEWED AND CHANGES ARE MADE WITHDRAWL OF CERTIFICATION TRANSFER OF COLORANT FROM ONE

CERTIFICATION CATEGORY TO ANOTHER

ADDITION OF NEW COLORS TO THE LIST

IDEAL CHARACTERISTICS

SAFE

MUST NOT INTERFERE WITH THERAPEUTIC EFFICACY

MUST NOT INTERFERE WITH PRESCRIBED ASSAY PROCEDURE

TYPES

DYES – LIQUID DYES COLORANTS IN THE RANGE 0.0005%

TO 0.001%

LAKE PIGMENT A FD&C lake is a pigment consisting of

a substratum of alumina hydroxide on which dye is adsorbed or precipitated

10 to 40% of colorant is used.

LAKES

FINE DISPERSIONS OR SUSPENSIONSPARTICLE SIZE RANGE 1microM to

30microMLESSER CHANCE OF SPECKLING WITH FINER PARTICLESVEHICLES USED : Glycerin,propylene glycol,sucrose based syrup

COLORANTS IN CAPSULES

COLORED EMPTY GELATIN CAPSULES

TWO COLORED CAPSULE

0.1% DYE IS USED

CONSIDERATIONS

SOLUBILITYpHpH stability of the preparation to be coloredPHOTOSTABLE :stored in amber colored bottlesOXIDATION POTENTIAL