SOLUBILIZATION

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Presented byNouman Farooq

Roll No. 68Pharm-D (1st Proff)

PharmaceuticsLahore Pharmacy College,

LMDC

Guided byMs. Kanwal

CONTENTS

• Introduction• Solubilization & its Importance• Mechanism of solubilization• Factors affecting solubilization• Solubilization Techniques

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Difference BetweenSolubility &

Solubilization

These are two different terms.

Solubility

• Maximum quantity of solute that can dissolve at CTP.

• Amount of Solute -> Solvent = Solubility of the substance

Expression for approximate solubility

Descriptive terms Relative amounts of solvents to dissolve 1 part of solute

Very soluble Less than 1

Freely soluble From 1-10

Soluble From 10-30

Sparingly soluble From 30-100

Slightly soluble From 100-1000

Very slightly soluble From 1000-10,000

Insoluble or practically insoluble More than 10,000

Problems with poor solubility

• Reduced drug efficiency • Reduced absorption of drug • May cause side effects

Solubilization• Physico-Chemical Property.

Solubilization definition • Thermodynamically stable solution • Addition of a component

SOLUBILIZATION

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Process of Solubilization

• Breaking of inter-ionic or inter–molecular bonds in the solute.

• Separation of solvent molecules.• Interaction.

Process of Solubilization

Process of Solubilization

Process of Solubilization

IMPORTANCE OF SOLUBILIZATION

An understanding of the solubility behavior of a drug is very important.• Parenteral formulations.• Oral formulations -> adequate solubility and

dissolution rate is required.• For entrance in systemic circulation.• Therapeutic effect.

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FACTORS AFFECTING SOLUBILITY

SOLUBILITY

TEMPERATURE

PRESSURE

NATURE OF SOLID

PARTICLE SIZE

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Factors affecting solubility:-

Particle Size: Kelvin equation

Where, S =is the solubility of infinitely large

particles S=is the solubility of fine particles

V= is molar volume γ= is the surface tension of the solid

r =is the radius of the fine particle

Temperature

• ∆Hs( heat of solution) = mole of solute is dissolved.

• Endothermic -> increases solubility.• Exothermic , decreases solubility.

Pressure

Pressure will affect solubility .• Gaseous solutes X Solubility• Solid and liquid = No effect .

Nature of the solid

Internal structure affects the solubility.• Crystalline = Low solubility.• Amorphous = High solubility.

Polymorphism

• The order for dissolution of different solid forms of a drug is in the next slide

Order of Dissociation of different solid form of drug

• Amorphous Form

• Metastable Polymorphous

• Stable Polymer

Solubilization techniques

I .PHYSICAL MODIFICATIONS A. Particle size reduction a. Micronization b. Nano suspension B. Modification of the crystal habit a. Polymorphs b. Pseudo polymorphs C. Drug dispersion in carriers a. Eutectic mixtures b. Solid dispersions c. Solid solutions D. Complexation a. Use of complexing agents E. Solubilization by surfactants a. Micro emulsions b. Self micro emulsifying drug delivery systems

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II. Chemical Modifications a. Changing in pH b. Using of salts

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CO-solvency

Enhancing weak electrolytes and non-polar solubility.• Addition of water miscible solvents is known

as co-solvency. • Formulation of parenteral.

• Ethanol, Sorbitol, Glycerin, Polyethylene glycol, propylene glycol etc.

CO-solvency

co-solvency is by • Interfacial tension• Contact angle• Polarity of the drug and water system

Example: Phenobarbitone is relatively insoluble in water but it solubility can be increased by using mixture of solvents like water, alcohol and glycerin

Addition of Surfactants

Enhance• Dissolution rate• Permeability of the drug Surfactants

• Surface tension • Micelles

Solid dispersion technique

• Particle size reduction• Increased rates of dissolution

Complexation• Reversible association of a substrate and

ligand molecule.

• Cyclo-dextrins, caffeine, urea.

Pharmaceutical Applications of Solubilization

• Wide Range.• Oil Synthesis. E.g. polysorbates 60

• Low solubility -> a problem.

Pharmaceutical Applications of Solubilization

• Compound-surfactant systems

e.g. iodine-surfactant system

Immediate availability.Oral bioavailability.Bioavailability & solubilityPossibilitiesDesirable dosage form. BackboneResearch

CONCLUSION

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