SOLUBILIZATION & TECHNIQUES OF SOLUBILIZATION

Prepared by:Gohil RiyazM.Pharm 1st yearDept.of pharmaceutics

CONTENTS

IntroductionImportant of SolubilityTechniques of solubilization a)Physical modification b)Chemical modification c)Micelleneous methodsReference

INTRODUCTION

SOLUBILITY: Solubility is defined in quantitative terms as concentration of solute in concentrated solution at a certain temperature, and in qualitative way it can be defined as a spontaneous interaction of two or more substance to form a homogeneous molecular dispersion.

SOLUBILIZATION: Solubilization can be defined as a preparation of thermodynamically stable isotropic solution of a substance normally insoluble or slightly soluble in a given solvent by introduction of an additional component or components.

The pharmacopoeia lists solubility in terms of number of millilitres of solvent required to dissolve 1g of solute. The Indian pharmacopoeia provides general terms to describe a given range.The descriptive term are given as:

DEFINATION PARTS OF SOLVENT REQUIRED FOR 1 PART OF SOLUBILITY

Very soluble <1

Freely soluble 1-10

Soluble 10-30

Sparingly soluble 30-100

Slightly soluble 100-1000

Very slightly soluble 1000-10000

Insoluble >10000

IMPORTANCE OF SOLUBILITY

Therapeutics effectiveness of a drug depends upon the bioavailability and ultimately upon the solubility of drug molecule.

It is important parameter to achieve desired concentration of drug in systemic circulation for pharmacological response to be shown.

Any drug to be absorbed must be soluble or present in the form of an aqueous solution at the site of absorption.

TECHNIQUES OF SOLUBILIZATION

A) Physical modification: a) Crystal habit modification: 1)Polymorphs 2)Amorphous 3)Pseudopolymorps b) Drug dispersion: 1)Eutectic mixture 2)Solid dispersion 3)Solid solution c) Lyophilisation:

a) Crystal habit modification:

1) Polymorphs: Polymorphs exist in a) stable form b) metastable forma) Stable form- shows low aqueous solublityb) Metastable form-shows high aqueous

solublitye.g: The polymorphic form III of riboflavin is

20 times more water soluble than the form I

2) Amorphous: They have greater aqueous solubility than the

crystalline form because the energy required to transfer e molecule from crystal lattice is greater than that required for amorphous solid.

e.g: Amorphous form of Novobiocin is 10 times more soluble than the crystalline form

3) Pseudopolymorphism(Hydrates & Solvates): The anhydrous form of drug has greater aqueous

solubility than the hydrates, because of the hydrates are already in interaction with water and therefore have less energy for crystal breakup in comparison to the anhydrous for further interaction with water.

e.g: Anhydrous form of theophylline have higher solubility in comparison to their monohydrate form.

The organic solvates have greater aqueous solubility than non solvates.

e.g: Chloroform solvates of griseofulvin more water soluble than their non solvate form.

b) Drug dispersion:

1) Eutectic mixture: When the eutectic mixtue is exposed to water

the soluble carrier dissolves leaving the drug in a microcrystalline state which solubilize rapidly.

e.g: Mixture of paracetamol and urea.

2) Solid dispersion: Prepared by solvent or co precipitation method. In it guest solute + solid carrier solvent Dissolved in a common volatile liquid solvent

such as alcohol. The liquid solvent is removed by evaporation

under reduced pressure or by freeze drying which results in amorphous precipitation of guest in crystalline carrier which solubilizes rapidly.

e.g: Amorphous sulfathiazole in crystalline urea.

3) Solid-solution:Two components crystallise together in a

homogeneous one phase system, because of reduction in particle size to the molecular level solid solution shows greater aqueous solubility.

e.g: Griseofulvin from such solid solution dissolves 6 to 7 times faster than pure griseofulvin

c) Lyophilisation: Amorphous powder with high degree of

interaction between drug and carrier like cyclodextrine it get in to porous—solubilized rapidly.

e.g: Indomethacin having low solubility in water----- increased by lyophilisation.

b) Chemical modification:1) Change of pH2) Complexation3) Salt formation4) Prodrug

1) Change of pH:

This can be achieved in two ways a) In situ salt formation b) Addition of buffers to formulation.e.g: Buffered aspirin tablet.

2) Complexation: The beta and gamma cyclodextrin having

ability to form molecular inclusion complexes with hydrophilic drug having poor aqueous solubility.

Cyclodextrin are versatile in having hydrophobic cavity of suitable enough to accomodate the lipophilic relatively hydrophilic ---- improved aqueous solubility

e.g: Barbiturates, Benzodiazepines.

3) Salt formation:

Salts have improved solubility in comparison to the original drug.

e.g: Alkali metal salts of acidic drugs like penicillin and strong acid salt of basic drugs like atropin are water soluble than parent drugs.

4) Prodrug : Solubility can be increased by conversion of

drug into prodrug.e.g: Chloroform and Tocopherols are poorly

aqueous soluble drugs, solubility increased by succinate ester prodrug of chloromphenicol and tocopherols.

c) Micellenious methos:

1) Use of surfectant 2) Cosolvency 3) Hydrotrophic agent

1) Use of surfactant: Surfactant reduced the interfecial tension. Enhance solubility by promoting wetting and

penetration of dissolution fluid into the solid drug particles.

e.g: Spironolactone(steroids)--- increased solubility by using surfactant(non ionic polysorbates).

2) Cosolvency: The polar water environment more non polar

like the solute- cosolvents facilitates solubilization.

e.g: PEG400 is improving the solubility of hydrochlorthiazide.

3) Hydrotrophic agent: Hydrotrophy desigate the increase in solubility

in water due to th presence of large amount of additives.

The mechanism related to complextion involving a weak interaction the hydrotrophic agent and solute.

e.g: Solubilization of theophylline with sodium acetate and sodium alginate.

REFERENCEText book of biopharmaceutics and

pharmacokinetics by brahmankar, page no.349-366

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