Preformulation Studies

Adina Institute of Pharmaceutical Sciences Sagar M P

Page 1

1. Introduction
Almost all drugs are marketed as tablets, capsules or both. Prior to
thedevelopment of these major dosage forms, it is essential that
certainfundamental physical and chemical properties of the drug molecule
and otherdivided properties of the drug powder are determined. This
information decidesmany of the subsequent events and approaches in
formation development. Thisfirst learning phase is known as preformulation.

Preformulation commence when a newly synthesized drug shows

sufficientpharmacologic promise in animal model to warrant evaluation in
man. Thesestudies should focus on those physiochemical properties of the
new compoundthat could affect drug performance and development of an
efficacious dosageform. A thorough understanding of these properties may
ultimately provide arationale for formulation design or support the need for
molecular modification.In the simplest case these preformulation
investigations may merely confirmthat there are no significant barriers to the
product development.
2. Definition
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Preformulation is the prerequisite of formulation, for the development

of safe and effective dosage form for clinical use.
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Preformulation involves the application of biopharmaceutical principlesto

the physicochemical parameters of drug substance are characterizedwith the
goal of designing optimum drug delivery system.
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A stage of development during which the physicochemical properties

of drug substance are characterized. Before beginning the
formalpreformulation programs the preformulation scientist must consider
thefollowing factors:-- The amount of drug available.- The physicochemical
properties of the drug already known.
Preformulation Studies

Adina Institute of Pharmaceutical Sciences Sagar M P

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- Therapeutic category and anticipated dose of compound.

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During the early development of a new drug substance, the syntheticchemist,

alone or in cooperation with specialists in other disciplines(including
preformulation), may record some data which can beappropriately
considered as preformulation data.
3. Correlation between Preformulation and formulation

Figure. Correlation between Preformulation and formulation

It is only on relatively few occasions that a drug as such may be
directlyadministered to a patient. Usually the medicament must be mixed
with theappropriate stabilizers, preservatives etc. and subjected to various
processes togive a practical dosage form, in other words the medicament
must formulated.Thus a dosage form must be act as a vehicle for drug
delivery. Theinformation generated out of exhaustive preformulation study
certainlyprovides the necessary platform. Selection of correct excipients in
correctproportion is an important step in the formulation development so as
toproduct development

Preformulation Studies

Adina Institute of Pharmaceutical Sciences Sagar M P

Page 3

4. Steps in Preformulation Process Pharmaceutical Research

4.1. Stability
a. Solid State(1)Temperature(2) pH-Solubility Profile(2) Light(3)
Humidityb. Solution(1) Solvent(2) pH(3) Light
4.2. Solid State Compatibility
a. TLC Analysisb. DRS Analysis
4.3. Physico-chemical Properties
a. Molecular weightb. Colorc. Odord. Particle size, Shape, and
Crystallinitye. Melting Pointf. Thermal Analysis Profile(1) DTA(2) DSC(3)
TGAg. Hygroscopicity Potentialh. Absorbance Spectra(1) UV(2) IR

Preformulation Studies

Adina Institute of Pharmaceutical Sciences Sagar M P

Page 4

i. Solubility(1)Water and Other Solvents(2) pH-Solubility Profile

(3) Salt Forms(4) Cosolvents(5) Complexation(6) Prodrugj. Effect of pH on

UV Spectrak. Ionization Constantm. Optical Activityn. Polymorphism
Potentialo. Solvate Formation
4.4. Physico-mechanical Properties
a. Bulk and Tapped Densityb. Compressibilityc. Photomicrograph
4.5. In Vitro Availability Properties
a. Dissolution of Drug Crystal Per seb. Dissolution of Pure Drug Pelletc.
Dissolution Analysis of Pure Drugd. Rat Everted Gut Technique
4.6. Other Studies
a. Plasma Protein Bindingb. Effect of Compatible Excipients on
Dissolutionc. Kinetic Studies