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 .
• Introduction
• Chemical and pharmaceutical
information
2.1 Information on active ingredients
Drug information (Generic name,Chemical
name or INN)
2.2 Physicochemical data
a. 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 study
Stability evaluation in market
intended pack at proposed storage
conditions
Packing specifications
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
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 PROFILE
BIOAVAILABILITY
CLINICAL EFFECTIVENESS
THERAPEUTIC 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

POWDERS
TABLETS
 SUSTAINED RELEASE
 ENTERIC COATED
CAPSULES
 HARD GELATIN
 SOFT GELATIN
SEMISOLID DOSAGE
FORMS
OINTMENTS
SUPPOSITORIES
PESSARIES
CREAMS
INHALATIONS
AEROSOLS
CONSTITUENTS OF A
DOSAGE FORM

DRUG
VEHICLE
PHARMACEUTICAL
INGREDIENTS AND EXCIPIENTS
DRUG
DATA FROM PREFORMULATION
STUDIES
eg:solubility data
stability data etc.
PHARMACEUTICAL
INGREDIENTS
ANDEXCIPIENTS

Produce drug in to final dosage

form
Solutions
 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
pharmaceutical
excipients
Non
propreitary,chemical,commercial
names
Empirical and chemical formulae
Pharmaceutical specifications
Chemical and physical properties
Incompatibilities
Interactions with other excipients
and drug substances
Regulatory status
Application in pharmaceutical
HARMONIZATION OF
STANDARDS

As per four Pharmacopeias

 U.S.P – N.F
 B.P
 European Pharmacopeia
 Japaneese Pharmacopeia
PALATABILITY
Liquids by oral route
Mask the disagreeable taste
Capsule or coated tablets
Chewable tablets to be
sweetened and flavored
Prediction 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
COLOURING AGENTS
USED FOR ESTHETIC ENHANCEMENT

TYPES
 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
study
Long term toxicity and
carcinogenicity
Five categories :
 Clear evidence of carcinogenic
activity
 Some evidence
 Equivocal evidence indicating
uncertainty

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
SUSPENSIONS
PARTICLE SIZE RANGE 1microM to
30microM
LESSER CHANCE OF SPECKLING
WITH FINER PARTICLES
VEHICLES USED :
Glycerin,propylene glycol,sucrose
based syrup
COLORANTS IN
CAPSULES
COLORED EMPTY GELATIN
CAPSULES

TWO COLORED CAPSULE

0.1% DYE IS USED

CONSIDERATIONS
SOLUBILITY
pH
pH stability of the preparation to
be colored
PHOTOSTABLE :stored in amber
colored bottles
OXIDATION POTENTIAL