olubility Enhancement by Micronization

1. SOLUBILITY ENHANCEMENT BY
MICRONIZATION
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Mr. Sagar Kishor Savale
[Department of Pharmaceutics]
avengersagar16@gmail.com
2015-2016
Department of Pharmacy (Pharmaceutics) | Sagar savale

2. Contents
1) What is solubility ?
2) Need of enhancing drug solubility
3) Different methods of enhancing solubility
4) Approximate solubility
5) Micronization technology
6) Pharmaceutical applications
7) Examples of miconization process
8) Reference.
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3. SOLUBILITY
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 The term solubility is defined as maximum amount of solute that can be
dissolved in a given amount of solvent.
 Solubility depends on:
 The physical form of the solid
 The nature and composition of solvent medium
 Temperature and pressure of system
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4. Need of enhancing solubility
 To enhance the solubility of poorly aqueous soluble drugs
 poorly aqueous soluble drugs are administered at much higher doses than
actually desired, leading to associated toxicity problems
 Enhancing bioavailability of poorly water soluble drug molecule
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5. Approximate solubility
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Terms Parts of solvent required to
dissolve one part of solute
Very soluble Less than 1parts
Freely soluble From 1-10 parts
Soluble From 10-30 parts
Sparingly soluble From 30-100 parts
Slightly soluble From 30-100 parts
Very slightly soluble From 1000-10,000 parts
Practically insoluble More than 10,000 parts
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6. Method used for solubility enhancement
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1. Physical modifications:
a. Particle size reduction
- Micronization
- Nanosuspension
b. Modification of the crystal habit
- Polymorphs
- Pseudopolymorphs
c. Drug dispersion in carriers
- Solid dispersions
- Solid solutions
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7. d. Complexation
- Use of complexing agents
(e.g. cyclodextrins and their derivatives)
e. Solubilization by surfactants:
- Microemulsions
- Self microemulsifying drug delivery systems (SMEDDS)
2. Chemical Modification:
a. Change of the pH
b. Use of buffer
c. Derivatization
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8. What do you mean by Micronization ?
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 Def : Micronization is a term used to describe size reduction where resulting
particle size is less than 10 microns. Micronization size reduction involves
acceleration of particles so that grinding occurs by particle-to-particle
impact or impact against solid surface.
 Micronization of drugs is done by –
jet mill and rotor stator colloid mills that result in a wide particle size
range between 0.1–25 µm.
 The micronization material had 99.9% of the particals samller than 10µm
diameter .
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9. Micronization Techniques
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1) Ball mill
2) Rotor sartor colloidal mill
3) Jet mill
4) Hammer mill
5) Super critical fluid
6) High pressure homogenization
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10. 1. Ball mill
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Principle:-
The ball mill is very widely used machine for fine size reduction. The
size reduction is achieved by two mechanism.
1. Impact of balls when they fall over the material
2. Shearing: When the balls slide over each other and give a rubbing action.
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11. 2.Hammer mill
Principle:-
Hammer mill based on the principle of impact.
i.e, When material is hit by an object moving at high speed or when the moving
particle strikes a stationary surface.
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12. 3.High pressure homogenization7
Principle:-
HPH uses energy of high pressure pump to achieve homogenization
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13. 4.Jet mill
Principle:-Fluid jet mill uses energy of fluid (high pressure air) to achieve ultra
fine grinding of pharmaceutical powders.
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14. The most studied SF-based micronization techniques are
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 Rapid Expansion of Supercritical Solutions (RESS)
 Supercritical Anti Solvent precipitation (SAS)
 Supercritical fluids Assisted Atomization (SAA)
 Particles generation from Gas Saturated Solutions (PGSS)
 Supercritical Carbon dioxide Assisted Nebulization (CAN-
BD) with a Bubble Dryer.
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15. What is Super Critical Fluid?
 A fluid is compressed beyond its Pc and heated beyond its Tc.
Why we choose CO2:
 nonflammable, nontoxic, Low dielectric constant, inexpensive, mild Tc.
Solubility
 Non polar or light molecules easily dissolve in CO2.
 Heavy molecules have a very poor solubility.
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16. PROCESS PRINCIPLE
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Drug is saturated with supercritical CO2, and the sudden change in
the fluid pressure causes rapid precipitation.
Drug is saturated with supercritical CO2, and the sudden diffusion of
CO2 into a drug solution causes drug precipitation.
Solubilization of supercritical CO2 in a liquid solution containing the
drug, and on its subsequent atomization using a thin wall nozzle.
Drug saturated with supercritical CO2 is rapidly cooled by adiabatic
expansion of CO2, and the solid dispersion precipitates in the form of
microparticles.
Drug saturated with supercritical CO2 is rapidly expanded to
atmospheric pressure to generate aerosols of micro bubbles and micro
droplets. Then aerosol plume is dried and mixes with nitrogen or air
to produce fine powders.
RESS
SAS
SAA
PGSS
CAN-BD

17. Reference
1. Martin, A, Bustamanate, P, and Chun, A, H, C, “Physical Pharmacy” B.I.
Wavely Pvt. Ltd, New Delhi, 1994; 4, 223.
2. Neuberg, C, Hydrotrophy, Biochem J. Pharm, 1989; 75(7), 577.
3. Osol, A, (Eds.) in: “Remington’s Pharmaceutical sciences” Mack Publishing
Company, Eastern Pennsylvania, 1990; 18, 203.
4. Indian pharmacopeia-2007,gove. Of India, ministry of health and family
welfare, published by the India Pharmacopoeia commission, Ghaziabad,
page no..143
5. Adam M.et. Al; solution and solubility.
http:www.cop.ufl.edu/safezone/prokai/pa5100/pha5110
6. Innovative milling and micronization thecniques for pharmaceutical
industry by sharon a.yaeger.
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7. Miller RH ,peters k., nanosuspensions for the formulation of poorly soluble
drug .1 prepartion by a size reduction technique. Int J pharm 1998; 160:229-237
8. R.S.Gaud,P.G.Yeole,A.V.Yadav,S.B.Gokhale,Text book of Pharmaceutics,
Published by Nirali Prakashan,Page no.152-155
9. Wong D. H., Kim M. S., Lee S., Jeong S.P., Hwang S.J. Improved physicochemical
characteristics of felodipine solid dispersion particles by supercritical anti-
solvent precipitation process. International Journal of Pharmaceutics, 2005;
301, 199-208.
10. Dohrn R., Bertakis E., Behrend O., Voutsas E., Tassios D. Melting point
depression by using supercritical CO2 for a novel melt dispersion
micronization process. Journal of Molecular Liquids, 2007; 131-132.
24/09/2014 18MICRONIZATION GOHIL VIKRANT

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