08-08-2012, 12:29 PM
REVIEW ON SOLID DISPERSIONS
[attachment=30538]
INTRODUCTION
The solubility is defined as the concentration of the undissolved solid in a solvent under a given set of conditions.
Step 1: Holes open in the solvent
Step 2: Molecules of the solid breaks away from the bulk
Step 3: The free solid molecule is integrated into the hole of the solvent.
DEFINITION
The term solid dispersion defined as “A dispersion of one or more active ingredients in an inert carrier or matrix in the solid state prepared by the melting, solvent or melt solvent method.
INTRODUCTION TO SOLID DISPERSION TECHNOLOGY:
The enhancement of oral bioavailability of poorly water soluble drugs remains one of the most challenging aspects of drug development.
Although salt formation, solubilization and particle size reduction have commonly been used to increase dissolution rate and thereby oral absorption and bioavailability of such drugs, there are practical limitations of these techniques.
The salt formation is not feasible for neutral compounds and the synthesis of appropriate salt forms of drugs that are weakly acidic or weakly basic may often not be practical.
Although particle size reduction is commonly used to increase dissolution rate, there is a practical limit to how much size reduction can be achieved by such commonly used methods as controlled crystallization, grinding, etc.
The use of very fine powders in a dosage form may also be problematic because of handling difficulties and poor wettability.
In 1961, Sekiguchi and Obi developed a practical method whereby many of the limitations with the bioavailability enhancement of poorly water-soluble drugs can be overcome, which was termed as “Solid Dispersion” .
SELECTION OF CARRIERS:
It is important that the carries chosen for the solid dispersion system should be readily soluble in water.
IDEAL PROPERTIES OF CARRIERS USED FOR SOLID DISPERSION
The carriers used for preparing solid dispersions should be:
Soluble in water (Insoluble in case of sustained action solid dispersion).
Non toxic.
Physiologically inert.
Have a relatively low pressure.
Physically and chemically complete with the drug.
Thermally stable up to its melting point.
E.g.:Citric acid, Succinic acid, Bile acid, Sterols, and polymers like PVP and PEG etc.
MECHANISM OF INCREASED DISSOLUTION RATE:
The enhancement in dissolution rate as a result of solid dispersion formulation, relative to pure drug varies from as high as 400 folds to less than two- fold.
Corrigan reviewed the current understanding of the mechanism of release from solid dispersion.
The increase in dissolution rate for solid dispersion can be attributed to a number of factors.
It is very difficult to show experimentally that any one particular factor is more important than another.
The main reasons postulated for the observed improvements in dissolution of these systems are as follows:
Reduction of particle size:
In case of glass, solid solution and amorphous dispersions, particle size is reduced to a minimum level.
This can result in an enhanced dissolution rate due to an increase in both the surface area solubilization.
b) Solubilization effect:
The carrier material, as it dissolves may have a solubilization effect on the drug.
This was shown to be the case for acetaminophen and chlorpropamide in urea as well as for numerous other drugs.
c) Wettability and dispersibility:
The carrier material may also have an enhancing effect on the wettability and dispersibility of the drug in the dissolution media.
This should retard any agglomeration or aggregation of the particles, which can slow the dissolution process.
Use of Surfactants in Solid Dispersion Systems:
The bioavailability of hydrophobic drugs can be increased by strategies designed to enhance the dissolution rate of the drug.
This has been achieved in many cases by forming a solid dispersion of the drug in a suitable carrier, often a hydrophilic polymer such as polyethylene glycol (PEG) ,lactose, mannitol, urea, polyvinyl pyrrolidone.
The drug is dispersed in the carrier by coprecipitation from a suitable solution containing both drug and carrier, by melting both components together, or by some other process involving a phase change.
METHODS OF PREPARING SOLID DISPERSIONS
a) Solvent evaporation method:
b) Modified Solvent evaporation method:
c) Melting /Fusion method:
d) Solvent melting method:
e) Kneading method:
f) Co-Grinding method:
g) Co-precipitation method (co-evaporates):
h) Spray drying method:
i) Gel entrapment technique:
j) Lyophilization technique:
k) Supercritical fluid (SCF) technology:
[attachment=30538]
INTRODUCTION
The solubility is defined as the concentration of the undissolved solid in a solvent under a given set of conditions.
Step 1: Holes open in the solvent
Step 2: Molecules of the solid breaks away from the bulk
Step 3: The free solid molecule is integrated into the hole of the solvent.
DEFINITION
The term solid dispersion defined as “A dispersion of one or more active ingredients in an inert carrier or matrix in the solid state prepared by the melting, solvent or melt solvent method.
INTRODUCTION TO SOLID DISPERSION TECHNOLOGY:
The enhancement of oral bioavailability of poorly water soluble drugs remains one of the most challenging aspects of drug development.
Although salt formation, solubilization and particle size reduction have commonly been used to increase dissolution rate and thereby oral absorption and bioavailability of such drugs, there are practical limitations of these techniques.
The salt formation is not feasible for neutral compounds and the synthesis of appropriate salt forms of drugs that are weakly acidic or weakly basic may often not be practical.
Although particle size reduction is commonly used to increase dissolution rate, there is a practical limit to how much size reduction can be achieved by such commonly used methods as controlled crystallization, grinding, etc.
The use of very fine powders in a dosage form may also be problematic because of handling difficulties and poor wettability.
In 1961, Sekiguchi and Obi developed a practical method whereby many of the limitations with the bioavailability enhancement of poorly water-soluble drugs can be overcome, which was termed as “Solid Dispersion” .
SELECTION OF CARRIERS:
It is important that the carries chosen for the solid dispersion system should be readily soluble in water.
IDEAL PROPERTIES OF CARRIERS USED FOR SOLID DISPERSION
The carriers used for preparing solid dispersions should be:
Soluble in water (Insoluble in case of sustained action solid dispersion).
Non toxic.
Physiologically inert.
Have a relatively low pressure.
Physically and chemically complete with the drug.
Thermally stable up to its melting point.
E.g.:Citric acid, Succinic acid, Bile acid, Sterols, and polymers like PVP and PEG etc.
MECHANISM OF INCREASED DISSOLUTION RATE:
The enhancement in dissolution rate as a result of solid dispersion formulation, relative to pure drug varies from as high as 400 folds to less than two- fold.
Corrigan reviewed the current understanding of the mechanism of release from solid dispersion.
The increase in dissolution rate for solid dispersion can be attributed to a number of factors.
It is very difficult to show experimentally that any one particular factor is more important than another.
The main reasons postulated for the observed improvements in dissolution of these systems are as follows:
Reduction of particle size:
In case of glass, solid solution and amorphous dispersions, particle size is reduced to a minimum level.
This can result in an enhanced dissolution rate due to an increase in both the surface area solubilization.
b) Solubilization effect:
The carrier material, as it dissolves may have a solubilization effect on the drug.
This was shown to be the case for acetaminophen and chlorpropamide in urea as well as for numerous other drugs.
c) Wettability and dispersibility:
The carrier material may also have an enhancing effect on the wettability and dispersibility of the drug in the dissolution media.
This should retard any agglomeration or aggregation of the particles, which can slow the dissolution process.
Use of Surfactants in Solid Dispersion Systems:
The bioavailability of hydrophobic drugs can be increased by strategies designed to enhance the dissolution rate of the drug.
This has been achieved in many cases by forming a solid dispersion of the drug in a suitable carrier, often a hydrophilic polymer such as polyethylene glycol (PEG) ,lactose, mannitol, urea, polyvinyl pyrrolidone.
The drug is dispersed in the carrier by coprecipitation from a suitable solution containing both drug and carrier, by melting both components together, or by some other process involving a phase change.
METHODS OF PREPARING SOLID DISPERSIONS
a) Solvent evaporation method:
b) Modified Solvent evaporation method:
c) Melting /Fusion method:
d) Solvent melting method:
e) Kneading method:
f) Co-Grinding method:
g) Co-precipitation method (co-evaporates):
h) Spray drying method:
i) Gel entrapment technique:
j) Lyophilization technique:
k) Supercritical fluid (SCF) technology: