PRESENTATION solubility

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TECHNIQUES FOR DETERMINATION AND IMPROVEMENT IN DRUG SOLUBILITY : 

1 TECHNIQUES FOR DETERMINATION AND IMPROVEMENT IN DRUG SOLUBILITY PRESENTED BY HETANGI RATHOD

Solubility is rate and extent of solute to go into solvent to get homogenize untill equilibria. : 

2 Solubility is rate and extent of solute to go into solvent to get homogenize untill equilibria.

DETERMINATION OF SOLUBILITY : 

3 DETERMINATION OF SOLUBILITY SATURATION METHOD SHAKE FLASK METHOD TITRATION METHOD POTENTIOMETRY SPECTROPHOTOMETRY LIQUID CHROMATOGRAPHY

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Techniques Of Solubility Enhancement I .Physical Modifications A. Particle size reduction a. Micronization b. Nanosuspension B. Modification of the crystal habit a. Polymorphs b. Pseudopolymorphs C. Drug dispersion in carriers a. Eutectic mixtures b. Solid dispersions c. Solid solutions : 

5 Techniques Of Solubility Enhancement I .Physical Modifications A. Particle size reduction a. Micronization b. Nanosuspension B. Modification of the crystal habit a. Polymorphs b. Pseudopolymorphs C. Drug dispersion in carriers a. Eutectic mixtures b. Solid dispersions c. Solid solutions

CHEMICAL MODIFICATION - Change of the pH - use of buffer - derivatization : 

6 CHEMICAL MODIFICATION - Change of the pH - use of buffer - derivatization

PHYSICAL METHOD a) MICRONIZATION Micronisation increases the dissolution rate of drugs through increased surface area . Conventional methods of particle size reduction - comminution and spray drying, - milling techniques using jet mill, rotor stator, colloid mills etc. Micronization is not suitable for drugs having a high dose number because it does not change the saturation solubility of the drug. : 

7 PHYSICAL METHOD a) MICRONIZATION Micronisation increases the dissolution rate of drugs through increased surface area . Conventional methods of particle size reduction - comminution and spray drying, - milling techniques using jet mill, rotor stator, colloid mills etc. Micronization is not suitable for drugs having a high dose number because it does not change the saturation solubility of the drug.

COLLOIDAL MILL: : 

8 COLLOIDAL MILL:

b) NANOSUSPENSION Nanosuspensions are sub-micron colloidal dispersion of pure particles of drug, which are stabilised by surfactants.- increase in dissolution rate due to larger surface area.- absence of ostwald ripening due to narrow size range of particle. : 

9 b) NANOSUSPENSION Nanosuspensions are sub-micron colloidal dispersion of pure particles of drug, which are stabilised by surfactants.- increase in dissolution rate due to larger surface area.- absence of ostwald ripening due to narrow size range of particle.

Techniques for production of nanosuspensiona) Homogenization: by - conventional homogenizers - sonicators - high shear fluid processorsb) Wet milling: Active drug in the presence of surfactant is defragmented by milling. : 

10 Techniques for production of nanosuspensiona) Homogenization: by - conventional homogenizers - sonicators - high shear fluid processorsb) Wet milling: Active drug in the presence of surfactant is defragmented by milling.

Other techniques for reduction of the particle size : - Recrystallisation - Supercritical fluid process - Spray drying : 

11 Other techniques for reduction of the particle size : - Recrystallisation - Supercritical fluid process - Spray drying

Supercritical fluid process : : 

12 Supercritical fluid process :

Spray dryer : : 

13 Spray dryer :

B. MODIFICATION OF THE CRYSTAL HABIT: polymorphism Amorphous >Metastable polymorph >Stable polymorph : 

14 B. MODIFICATION OF THE CRYSTAL HABIT: polymorphism Amorphous >Metastable polymorph >Stable polymorph

Solubilization by surfactants: Microemulsion- A microemulsion is a four-component system composed of external phase, internal phase, surfactant and cosurfactant.- Surfactant having HLB value greater than 18 acts as solubilising agent. : 

15 Solubilization by surfactants: Microemulsion- A microemulsion is a four-component system composed of external phase, internal phase, surfactant and cosurfactant.- Surfactant having HLB value greater than 18 acts as solubilising agent.

II. CHEMICAL MODIFICATIONS :-1) By change of pHFor organic solutes that are ionizable, changing the pH of the system may be simplest and most effective means of increasing aqueous solubility. change of pH by 1 fold increase solubility by 10 fold : 

16 II. CHEMICAL MODIFICATIONS :-1) By change of pHFor organic solutes that are ionizable, changing the pH of the system may be simplest and most effective means of increasing aqueous solubility. change of pH by 1 fold increase solubility by 10 fold

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2) Use of buffer Buffer maintains the pH of the solution overtime and it reduces or eliminate the potential for precipitation upon dilution. On dilution pH alteration occurs that decrease solubility .If it changes by one pH unit ,that decrease ionization of the drug and solubility decreases by 10 fold. MARKET PRODUCT BUFFERMithohexital sodium Na2CO3 pH 9-11 Phenytoin sodium NaOH pH 10-12.3 : 

18 2) Use of buffer Buffer maintains the pH of the solution overtime and it reduces or eliminate the potential for precipitation upon dilution. On dilution pH alteration occurs that decrease solubility .If it changes by one pH unit ,that decrease ionization of the drug and solubility decreases by 10 fold. MARKET PRODUCT BUFFERMithohexital sodium Na2CO3 pH 9-11 Phenytoin sodium NaOH pH 10-12.3

3) Derivatization It is a technique used in chemistry which transforms a chemical compound into a product of similar chemical structure, called derivative.derivatives have different solubility as that of aduct. it is used for quantification of aduct. formation of esters and amides via acyl chlorides. : 

19 3) Derivatization It is a technique used in chemistry which transforms a chemical compound into a product of similar chemical structure, called derivative.derivatives have different solubility as that of aduct. it is used for quantification of aduct. formation of esters and amides via acyl chlorides.

OTHER TECHNIQUES * Cosolvency: cosolvents are prepared by mixing miscible or partially miscible solvents Cosolvents have some degree of hydrogen bond donating and hydrogen bond accepting ability as well as small hydrocarbon rigions. The resulting solution has intermediate to that of organic solvent and water that reduce water water interaction. Aquous solvent - Etahnol,sorbitol, glycerin, propylyne glycol,polyethylene glycol Non aquous solvent - glycerol dimethyl ketal,glycerol formal, glycofurol, dimethyl acetamide , ethyl carbonate : 

20 OTHER TECHNIQUES * Cosolvency: cosolvents are prepared by mixing miscible or partially miscible solvents Cosolvents have some degree of hydrogen bond donating and hydrogen bond accepting ability as well as small hydrocarbon rigions. The resulting solution has intermediate to that of organic solvent and water that reduce water water interaction. Aquous solvent - Etahnol,sorbitol, glycerin, propylyne glycol,polyethylene glycol Non aquous solvent - glycerol dimethyl ketal,glycerol formal, glycofurol, dimethyl acetamide , ethyl carbonate

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21 SOME PERANTRALPRODUCT THAT CONTAIN COSOLVENT Busulfan(Busulfex) 67% PEG 400 +33% N,N DMA Diazepam (Valium) 10% ethanol + propyline glycol Digoxin( Lanolin) 10% ethanol + propyline glycol Epinephrine(susphrin) 32.5% glycerin

COMPLEXATIONInclusion complexes are formed by the insertion of the nonpolar molecule or the nonpolar region of one molecule (known as guest) into the cavity of another molecule or group of molecules. taxol ,clofibrat ,celecoxib Cyclodextrins : : 

22 COMPLEXATIONInclusion complexes are formed by the insertion of the nonpolar molecule or the nonpolar region of one molecule (known as guest) into the cavity of another molecule or group of molecules. taxol ,clofibrat ,celecoxib Cyclodextrins :

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Hydrotrophy:Hydrotrophy designate the increase in solubility in water due to the presence of large amount of additives. The mechanism - related to complexation involving a weak interaction between the hydrotrophic agents (sodium benzoate, sodium acetate, sodium alginate, and urea) and the solute.Example: Solubilisation of Theophylline with sodium acetate and sodium alginate. : 

24 Hydrotrophy:Hydrotrophy designate the increase in solubility in water due to the presence of large amount of additives. The mechanism - related to complexation involving a weak interaction between the hydrotrophic agents (sodium benzoate, sodium acetate, sodium alginate, and urea) and the solute.Example: Solubilisation of Theophylline with sodium acetate and sodium alginate.

REFERENCES 1) Leon Lachman; Herberta.Lieberman; Joseph L.Kanig The Theory And Practise Of Industrial Pharmacy . 3rd edition,pp 458. 2) Encyclopedia of pharma technology , pp2466 3) Alfred Martin.Physical Pharmacy , fourth edition, pp 212. 4) Solubility, From Wikipedia, the free encyclopedia. Retrieved from http://en.wikipedia.org/wiki/Solubility 5) Spray drying From Wikipedia, the free encyclopedia. Retrieved from http://en.wikipedia.org : 

25 REFERENCES 1) Leon Lachman; Herberta.Lieberman; Joseph L.Kanig The Theory And Practise Of Industrial Pharmacy . 3rd edition,pp 458. 2) Encyclopedia of pharma technology , pp2466 3) Alfred Martin.Physical Pharmacy , fourth edition, pp 212. 4) Solubility, From Wikipedia, the free encyclopedia. Retrieved from http://en.wikipedia.org/wiki/Solubility 5) Spray drying From Wikipedia, the free encyclopedia. Retrieved from http://en.wikipedia.org

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26 Thank you