pharmaceutical preformulation

Prepared By-KULDIP DEKAKUMAR SAMUDRA GUPTA KAUSHIKHIRAKJYOTI SARMA GUIDED BY-

Dr. B. M. Mazumder

CONTENTS :- DEFINATION AND IMPORTANCE OF

PREFORMULATION IN PHARMACY. STEPS INVOLVED IN

PREFORMULTION. ORGANOLEPTIC PROPERTIES. PURITY, PARTICLE SIZE SHAPE AND

SURFACE AREA. SOLUBILITY AND DISSOLUTION OF

DRUG SUBSTANCE CHEMICAL REACTION INVOLVING

DRUG EXCIPIENT INTERACTIONS AND FACTORS AFFECTING ABSORPTION OF DRUGS.

DEFINATION OF PREFORMULATION:-

“PREFORMULATION IS A BRANCH OF PHARMACY WHICH DEALS WITH THE INVESTIGATION OF PHYSICAL AND CHEMICAL PROPERTIES OF A

DRUG SUBSTANCE ALONE OR WHEN COMBINED WITH EXCIPIENTS” It is

the characterization of the physical and chemical properties of a drug, especially a newly discovered drug.

IMPORTANCE OF PREFORMULATION IN PHARMACY:-

It was introduced at 1960 Preformulation testing is the first step in the

rational development of dosage form of a drug substance.

Preformulation forms an indespensible part of the inovator companey as well as generic companies.

Preformulation testing generate information useful to the formulator in developing stable and bioavilable dosage forms.

The necessity of preformulation is not only acknowledged by most companies it is to a certain extent prerequisite and forms back bone for R&D.

INFORMATION THAT A PREFORMULATOR OF PHARMACEUTICAL COMPANEY MUST SUPPLY

Solubility, dissolution, partition coefficient, ionization constant, pka and kp values of the drug.Crystall properties and polymorphism.Density, hygroscopicity, flowability, wetability and stability studies.Micromeritics considerations such as – shape, size, surface area, crystal habits etc..Compatibility with other compounds .Purity conformation by methods like-

HPLC, TLC, HPTLC ETC..

Preformulation Drug Characterization in a Structured Program

Program of Analytical Preformulation

“STEPS IN PREFORMULATION”

“PREFORMULATION MAY INCLUDE SAVERAL STEPS IN ORDER TO SATSFY THE LAVELS OF QUALITY AND

PURITY, OF THE PREFORMULATION PROCESS”

“THE STEPS IN PREFORMULATION ENSURE ITS EFFICIENCY”

Steps in Preformulation Process Pharmaceutical Research1. Stability i. Solubility

a. Solid State (1) Water and Other Solvents (1) Temperature (2) pH-Solubility Profile (2) Light (3) Salt Forms (3) Humidity (4) Cosolventsb. Solution (5) Complexation (1) Solvent (6) Prodrug (2) pH j. Effect of pH on UV Spectra (3) Light k. Ionization Constant

2, Solid State Compatibility l. Volatilitya. TLC Analysis m. Optical Activity b. DRS Analysis n. Polymorphism Potential

3. Physico-chemical Properties o. Solvate Formationa. Molecular Structure and Weight 4. Physico-mechanical Propertiesb. Color a. Bulk and Tapped Densityc. Odor b. Compressibilityd. Particle size, Shape, and Crystallinity c. Photomicrographe. Melting Point 5. In Vitro Availability Propertiesf. Thermal Analysis Profile a. Dissolution of Drug Crystal Per sec. (1) DTA b. Dissolution of Pure Drug Pellet (2) DSC c. Dissolution Analysis of Pure Drug (3) TGA d. Rat Everted Gut Techniqueg. Hygroscopicity Potential 6. Other Studiesh. Absorbance Spectra a. Plasma Protein Binding (1) UV b. Effect of Compatible Excipients (2) IR on Dissolution

c. Kinetic Studies of Solution Degradation d. Use of Radio-labeled Drug

The formal preformulation study should start at the point after biological screening, a decision is made for further development of the compound in clinical trials.

Before embarking upon a formal program, the preformulation scientist must consider the following:

1. The available physicochemical data (including chemical structure, different salts available)

2. The therapeutic class of the compound and anticipated dose

3. The supply situation and the development schedule (i.e., the time available)

4. The availability of a stability-indicating assay5. The nature of the information the formulator

should have or would like to have

“ORGANOLEPTIC PROERTIES”

1. ORGANOLEPTIC PROPERTIES “Organoleptic Properties are those properties

which are evaluated after an impression on the organs of sense”

It refers to the evaluation of drugs by properties like –colour, odour, taste, size, shape and special features like touch, texture, etc..it is a technique of qualitative evaluation based on the study of morphological and sensory profile of whole drugs.

The aromatic odour of fruits, sweet taste of liquorice, the ovoid tears of gum acacia are some examples of this type of evaluation.

SOME EXAMPLE OF ORGANOLEPTIC EVAULATION:-

RIBBONS OF TRAGACANTH DISC SHAPE OF NUX VOMICA

COLOUR Colour can be useful, while describing different

batches of drug, it can sometimes be used as an indicator of solvent presence or more importantly of degradation.

In addition subtle difference in colour due to particle size distribution.

Colour of various drug formulation may indicate the degradation process,the colour of certain types of formulation can be improved by adding certain dyes.

ODOUR Odour plays an important role in drug formulation and any strong odour should not be present for consumers acceptance of the consumers finished product.(such as capsules, tablets, syrups etc..)

Odour prrovides an indication of the quality of formulation.eg:-characteristic odour of acetic acid in degradation of aspirin.

Presence of odour may also be the characteristic of the drug.eg:- vitamins

TASTE:Taste of the formulated drug plays an important role in consumers acceptance.

Unpalatable drugs which donot have good taste, problem may be solved by incorporation of- Flovouring agents. Excipients. Coating.