The document discusses solid dispersion and complexation techniques for improving the solubility and bioavailability of poorly soluble drugs. Solid dispersion involves combining a drug with a hydrophilic carrier to improve its dissolution rate. Types of solid dispersions include solid solutions, eutectic mixtures, and glass suspensions. Preparation techniques include hot melt, solvent evaporation, melt extrusion, and kneading. Complexation, such as drug-cyclodextrin inclusion complexes, enhances drug solubility and stability. These techniques are important for formulating oral drugs that are limited by poor solubility.

1. MALLA REDDY COLLEGE OF PHARMACY
Maisammaguda, Dhulapally (post via Hakimpet), Sec-bad-14
SSOOLLIIDD
DDIISSPPEERRSSIIOONN &&
CCOOMMPPLLEEXXAATTIIOONN
Presented by
J.Jagan (256213886013)
Guided by
Dr. Yasmin Begum
H.O.D. Dept. of Pharmaceutics
Malla Reddy College of Pharmacy

2. Contents
* Solubility
* Advantages
* Importance
* Solid dispersion
* Types of solid Dispersion
* Preparation Techniques
* Complexation

3. Solubility
* 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.

4. Advantages
* Increased bioavailability
* Fast absorption
* Patient compliance
* No shaking
* No gritty particles are observed.

5. Importance
* Selection of solvent for dosage form.
* Information about the structure, inter molecular forces.
* Selection of dissolution medium.
* Separation of mixtures.
* Separation of optical isomers.

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

7. Introduction
* 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

8. Types of solid dispersion
* Solid eutectic mixture.
* Solid solutions.
* Glass solutions & suspension.
* Amorphous precipitations in crystalline carriers.

9. Solid Eutectic mixture
* 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.

10. Glass solution & suspension
* 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.

11. Solid solution
* 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.

12. Amorphous precipitations in
crystalline carrier
* 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.

13. Preparation techniques
* Holt-melt method (fusion method )
* Solvent evaporation method
* Holt melt extrusion
* Kneading method

14. Hot melt method
* 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

15. Solvent evaporation 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

16. Hot-melt extrusion
* 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.

17. Kneading method
* 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.

18. Complexation
* 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

19. Inclusion complexes
* 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.

20. * 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.

21. Conclusion
* 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.

22. Reference:
* 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