MALLA REDDY COLLEGE OF PHARMACYMaisammaguda, Dhulapally (post via Hakimpet), Sec-bad-14

SOLID SOLID DISPERSION DISPERSION

& & COMPLEXATICOMPLEXATI

ONON

Presented by J.Jagan

(256213886013)

Guided byDr. Yasmin Begum

H.O.D. Dept. of Pharmaceutics

Malla Reddy College of Pharmacy

Solubility Advantages Importance Solid dispersion Types of solid Dispersion Preparation Techniques Complexation

Contents

Solubility is the property of a solids, liquid or gaseous chemical substance called solute to dissolve in a solid, liquid or gaseous solvent to form a homogenous solution of the solute in the solvent. The solubility term is defined as maximum amount

of solute that can be dissolved in a given amount of solvent.

The solubility of a substance fundamentally depends on the solvent used as well as temperature & pressure.

Solubility

Increased bioavailability

Fast absorption

Patient compliance

No shaking

No gritty particles are observed.

Advantages

Selection of solvent for dosage form.

Information about the structure, inter molecular forces.

Selection of dissolution medium.

Separation of mixtures.

Separation of optical isomers.

Importance

The term solid dispersion refers to a group of solid products consisting of atleast two different components, generally a hydrophilic matrix and hydrophobic drug.

Solid dispersion

The concept of solid dispersion was originally proposed by Sekiguchi & obi.

Solid dispersion represents a useful pharmaceutical technique for increasing the dissolution, absorption & therapeutic efficacy of drugs in dosage forms.

The solubility of celecoxib, halofantrine, ritonavir can be improved by solid dispersion using suitable hydrophilic carriers

Introduction

Solid eutectic mixture.

Solid solutions.

Glass solutions & suspension.

Amorphous precipitations in crystalline carriers.

Types of solid dispersion

A simple eutectic mixture consists of two components which are completely miscible in liquid state but to a limited extend in solid state.

These are prepared by rapid solidification of fused melt of two components.

When a mixture of poor water soluble drug & water soluble carrier is dissolved in aqueous medium, the carrier is dissolved rapidly, releasing very fine crystal of drug.

Solid Eutectic mixture

A glass is a homogenous glassy system in which solute dissolves in the glassy system.

A glass suspension refers to a mixture in which precipitated particles are suspended in a glassy solvent.

Characterization of glassy state is transparency & brittleness below the glass transition temperature.

Glass solution & suspension

In a solid solution, the two components crystallize together in a homogenous one phase system.

In continuous solid solution, the two components are miscible in the solid state in all proportions.

In discontinuous solid solutions, the solubility of each of the components in the other component is limited.

Solid solution

In the group of dispersions drug is precipitated out in amorphous form while in simple eutectic mixture is in crystalline form.

Example : sulphathiazole in crystalline urea.

Amorphous precipitations in crystalline carrier

Holt-melt method (fusion method )

Solvent evaporation method

Holt melt extrusion

Kneading method

Preparation techniques

In this method, the physical mixture of a drug & water soluble carrier was heated directly until it melted.

The melted mixture was the cooled & solidified rapidly in an ice-bath under vigorous stirring..

The final solid mass was crushed, pulverized & sieved, which can be compressed into tablets with the help of tableting agents.

Advantages: Simplicity economy

Hot melt method

Tachibana & Nakumara were the first to dissolve both the drug & the carrier in a common solvent and then evaporate the solvent under vacuum to produce a solid solution. This enabled them to produce a solid solution of the

highly lipophillic β-carotene in the highly water soluble carrier polyvinylpyrolidone.

Advantages: Thermal decomposition of drugs are carriers can be

prevented because of the low temperature required for the evaporation of organic solvents.

Disadvantage: High cost of preparation Difficulty in completely removing liquid solvent

Solvent evaporation method

Holt-melt extrusion is essentially the same as the fusion method except that intense mixing of the components is induced by extruder.

Just like in the traditional fusion process, miscibility of drug and matrix can be a problem.

High shear forces resulting in high local temperature in the extruder is a problem for heat sensitive materials.

Hot-melt extrusion

Drug & carrier weighed , they are mixed together, use motor & pestle to reduce the size of the both drug & carrier.

Water-methanol mixture 3:1 ratio was added to the above mixture . The solution was mixed well and slurry was collected by filtration and dried in hot-air oven for 2hrs at 500C

Then dried mass was collected further dried in desiccated for 12hrs.

Then the solid dispersion passed to sieve no:80 to obtained uniform particle size.

Kneading method

The complex may be considered as a species of definite substrate to ligand stoichiometry which can be formed in an equilibrium process in solution and also may exists in solid state.

Advantages: To enhance the aqueous solubility Drug stability

Complexation

Lipophilic drug –cyclodextrin complexes, commonly known as inclusion complexes.

It can be formed simply by adding the drug and excipient together, resulting in enhanced drug solubilization.

Cyclodextrins are a group of structurally related cyclic oligosaccharides that have a polar cavity and hydrophilic external surface.

Inclusion complexes

Hydrophilic cyclodextrins are non toxic in normal doses while lipophilic ones may be toxic

Hence methyl, hydroxyl propyl, sulphoalkylated and sulphated derivatives of natural cyclodextrins that posses improved aqueous are preferred for pharmacy use

Cyclodextrins an also used as membrane permeability enhancer and stabilizing agents.

For orally administered drugs solubility is one of the rate limiting parameter to achieve their desired concentration in systemic circulation of pharmaceutical response.

Problem of solubility is a major challenge for formulation scientist.

Increasing number of poorly water soluble drug candidates as well as improvements in solid dispersion manufacturing methods strongly favor the roll of solid dispersion in solubility enhancement of poorly water soluble drugs.

Conclusion

International Journal of Pharmaceutical sciences review and Research

Remington the science and practice of pharmacy

Text book of essentials of physical pharmacy by C.V.S. Subhramanyam

www.ncbi.nlm.nih.gov

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