Preformulation study of semisolid, need, objective, physicochemical parameter.

1. PREFORMULATION OF
SEMISOLIDS
PRESENTED BY- GUIDED BY-
Mr. Shubham J Gore Dr.V.V.Pande
F.Y.M Pharm HOD of Pharmaceutics
(Pharmaceutics) Department.
Sanjivani College of Pharmaceutical Education and Research,
Kopargaon.
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2. CONTENTS
 Introduction
 Objective
 Need
 Physicochemical Parameters
 Conclusion
 References
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3. INTRODUCTION
 Definition
 It can be defined as an investigation of physical
& chemical properties of a drug substance alone
& when combined with exipients.
or
 It is the study of physicochemical property of
active pharmaceutical ingredient along with
excipient before the formulation of dosage form.
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4. OBJECTIVE
 To develop the pharmaceutically elegant
dosage form. (safe effective & stable)
 It is important to have an understanding of
the physical description of a drug substance
before dosage form devolopment.
 It is the first step in rational devolopment of a
drug substance before dosage form
devolopment.
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5. THE SEMI SOLIDS INCLUDE:
Gel Ointment Cream
Paste
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6. NEEDS OF PREFORMULATION
 Preformulation is to provide and understand information
regarding:
1. The degradation process
2. Any adverse condition relevant to drug.
3. Bioavailability
4. Pharmacokinetics and formulation of similar compounds.
5. Toxicity
6. It provides physicochemically stable and biopharmaceutically
suitable dosage form. 6

7. OUTLINE OF THE PRINCIPLE AREAS OF
PREFORMULATION AND RESEARCH
 1.Bulk characterization - Crystallinity and Polymorphism
- Hygroscopicity
- Fine Particle Characterisation
- Bulk Density
- Power flow property
 2. Solubility Analysis - Ionisation Constant –pka
- PH solubility profile
- Common ion effect –ksp
- Thermal effect
- Solubilization
- Partition coefficient
- Dissolution
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8.  3. Stability Analysis -Stability in formulation
- Solution stability
- Ph rate profile
- Solid state stability
- Bulk stability
- Compatibility
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9. PHYSICOCHEMICAL PARAMETER
 Penetration
 Solubility
 Texture analysis
 Effect of Light
 Salt formation
 Degradation pathways
 Partition coefficient
 Spreadability
 Hygroscopicity
 Fine particle characterisation
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10. 1 .PENETRATION
 We need to optimize the delivery of drug through
various skin layers to provide maximum therapeutic
effect .
 The penetration of drug through skin is measured by
in-vivo and in-vitro studies.
 In in-vitro techniques the permeation through skin is
measured directly where sampling is carried out
immediately below the skin surface this is in
contrast with most of the in-vivo method which
measure systemic level of drug.
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11. 11

12. 12

13. 2. SOLUBILITY
 The solubility of compound in the vehicle need to
be determined because different solubility
problems can be arise like.
Crystal formation
Precipitate formation
Coagulation
 If the system is supersaturated it shows crystal
growth.
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14. METHODS
 Shake flask method
 Computational screening method
used for prediction of intrinsic solubility.which is
based on lipophilicity and molecular surface
area.
 Miniature device
It was devololped for measuring aq.equilibrium
solubility during drug discovery only 1 mg of
compound it was possible to determine the
entire PH solubility profile.
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15. 3.TEXTURE ANALYSIS
 Texture analysis used to evaluation of mechanical
characteristic where a material is subjected to a
controlled force from which a deformation curve of
its response is generated.
two types of mechanical characteristic-
1.Primary
2.Secondary
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16. 1.Primary characteristic-
 Hardness
 Springiness
 Adhesiveness
 Cohesiveness
2.Secondary characteristic-
 Brittleness
 Gumminess
 Chewiness
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17. WHY MEASURE TEXTURE?
Consumer product succeed in the marketplace in
part because their textural characteristics are
pleasing to customer.
Application-
 Food industry
 Cosmetics
 Pharmaceutical
 Materials
eg-packaging,rubber,grease,wax
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18. PROPERTIES MEASURE
 Ripeness
 Yield point
 Spreadability
 Consistency
 Adhesiveness
 Elasticity
 Hardness
 Cohesiveness
 Breaking point
 Gel strength
 Gumminess
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19. 4 EFFECT OF LIGHT
 The stability of compound due to the presence of
light affected or not need to be check.
for example –
Diethanol shows a distinct instability in paraffin
due to light but stable when protect from light.
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20. 5.SALT FORMATION
 It improve the solubility of the drugs.
 A salt is a chemical combination of the ionizable
component-one is acidic and one is basic relative to
each other.
 If the Pka(acid)and Pka (basic) are close , a stable
salt may not form.
 When a salt formation is limited of molecule then
need to synthesis prodrugs.(Ex esters and amides)
 Some molecules are not form salt because it does
not dissociate in solvent.(alcohol and steroid)
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21. 6.DEGRADATION PATHWAY
a) Hydrolysis
 Hydrolysis is a solvolysis process in which (drug)
molecules interact with water molecules to yield
breakdown products of different chemical
constitution.
 A great number of medicinal agents are esters or
contain such other groupings as substituted amides,
lactones, and lactams which are susceptible to the
hydrolytic process.
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22. b)Oxidation-
 Oxidation reaction and reduction reaction are known as
reduction which involve either transfer of oxygen or
transfer of hydrogen
 Oxidation is promoted by presence of oxygen and
reduction can be initiated by the action of heat
Light
Trace element
Metal ion
 That produce organic free radicals these radicals propogate
the oxidation reaction
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23.  C)Racemization-
 Hydrolysis and oxidation are main mechanism by
which drug can be decompose
 Racemization is another way in which compound
can change in solution
For example- ropivacain hydrochloride
 Ropivacain is highly stable against hydrolysis but it
can undergoes racemization reaction and convert
from s-form to
R-form via pseudo first order reversable kinetics
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24. 7.PARTITION COEFFICIENT
 Partition coefficient influence permeation of a drug across
biological membrane.
 It is the ratio of unionized drug distributed between organic
and aqueous phase at equilibrium.
P o/w = ( C oil / C water ) equilibrium
Thus in any formulation, the lipophilic /hydrophilic
balance should always be maintained to yield a perfect
formulation.
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25. Drug with extremely high partition co-efficient (i.e. very oil-soluble )
readily penetrate the membranes.
While drugs with excessive aqueous solubility i.e. low oil/water
partition co-efficient cannot penetrate the membrane
Importance
• Partition coefficient is mainly required:
•
• To determine hydrophilic and lipophilic nature of drug
substance
• To determine bioavailability of drug
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26. 8. HYGROSCOPICITY
 Many compound and salt are sensitive to the presence of water
vapour and moisture.
 when a drug molecule come in contact with moisture it retain
water by capillary condensation or surface adsorption.
 The moisture can affect the stability of drug and there
formulation.
 Absorption and equilibrium moisture content depends on the
Atmospheric humidity
temperature
surface area
 Other hygroscopic substance adsorb water because of hydrate
formation or specific site adsorption
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27. HYGROSCOPICITY CLASSIFICATION
Class-1 Non- hygroscopic Essentially no moisture
increases occur at
relative humidity below
90%
Class-2 Slightly-hygroscopic Essential no moisture in
occur at relative
humidity below 80%
Class-3 Moderately-hygroscopic Moisture content does
not increases more than
5% after storage for 1
week at relative
humidity below 60%
Class-4 Very-hygroscopic Moisture content
increases may occur at
relative humidity as low
as 40 to50% 27

28. 9 .FINE PARTICLE CHARACTERIZATION
 Dissolution and chemical reactivity of compound is affected by
 Size
 Shape
 Surface morphology of drug particle
 In general each new drug should be tested during preformulation to
ensure homogeneous in sample and maximum surface area for
interaction
 For determination of size coulter counter method are use
 For measurement of surface area BET(Brunauer ,Emmett and
Teller)nitrogen adsorption technique are use
 For detection of surface Topography , scanning electron
microscopy (SEM) are use.
 For particle size measurment we are used zetasizer or masterizer.
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29. CONCLUSION
 It deals with the study of design and development of
dosage form.
 Preformulation studies are very important as it deals
with stability ,safety ,quality of the dosage form.
 Preformulation study give idea about the
pharmacokinetic, pharmacodynamic parameter.
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30. REFERENCES
1) Leon Lachmen ,Lieberman H.A., The theory and practices of
industrial pharmacy ,published by UARGHESE publishing
house,dader,bombay,third edition,1990, page no: 171-195.
2) Mark gibson.Pharmaceutical preformulation & formulation
,published by Interpharma /CRC ,Florida 2004,special Indian
edition ,Page no :21-35 ,515-51
3) Desu prasanna kumar,G.Vaishnavi,K.Divya,U.Lakshmi.An
Overview on Preformulation Studies;Indo American Journal of
Pharmaceutical Sciences.
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31. QUESTIONS
1. Discuss bulk characterization and solubility studies in
preformulation.(2008-pattern,2013-14)
2. Explain concept and importance of preformulation. Discuss
preformulation parameter for convensional dosage form.(2013-
pattern,2015)
3.Preformulation studies of conventional tablet.(2013 pattern,2013-
14)
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32. THANK
YOU……
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