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Solubilization
- 1. Seminar on Solubilization BY GAJANAN V NAIK MPHARM IST YEAR ( IIND SEM ) PHARMACEUTICS Swami Ramanand teerth Marathwada University, Nanded. School of Pharmacy
- 2. Contents ļµ What issolubility & solubility expressions ? ļµ Importance of solubility & Problems with poor solubility. ļµ What is solubilization? ļµ Process of solubilization. ļµ Methods of increasing solubility.
- 3. What is solubility& solubility expressions ? ļµ Solubility :- ļµ In quantitative terms - as the concentration of solute in a saturated solution at a certain temperature. ļµ In a qualitative way, it can be defined as the spontaneous interaction of two or more substances to form a homogeneous molecular dispersion. ļµ Solubility expressions:- ļµ The solubility of a drug may be expressed in a number of ways. The United States Pharmacopeia (USP) describes the solubility of drugs as parts of solvent required for one part solute. Description Parts of solvent required one part of solute Very soluble < 1 Freely soluble 1 - 10 Soluble 10 - 30 Sparingly soluble 30 - 100 Slightly soluble 100 - 1000 Very slightly soluble 1000 - 10,000 Insoluble > 10,000 1
- 4. Importance of solubility& Problems with poor solubility? ļµ Importance: - ļµ It is an important parameter to achieve desired concentration in systemic circulation. ļµ Solubility behavior of the drug is a one of the important aspects of preformulation testing for poorly soluble drug ļµ Problems with poor solubility: - ļµ Reduced drug efficiency ļµ Reduced absorption of drug ļµ May cause side effects 2
- 5. What is solubilization? ļµSolubilization: ļµ It can be defined as the preparation of a thermodynamically stable isotropic solution of a substance normally insoluble or very slightly soluble in a given solvent by the addition of component or components or by any suitable methods. ļµ Eg. 3
- 6. Process of solubilization4 ļµ Process of solubilization:- A. Breaking of inter-ionic or interāmolecular bonds in the solute B. Separation of solvent molecules to provide space for the solute C. Interaction between the solvent and solute molecule or ion A. Breaking of inter-ionic or interāmolecular bonds in the solute
- 7. Process of solubilization B.Separation of solvent molecules to provide space for the solute C. Interaction between the solvent and solute molecule or ion 5
- 8. Methods of increasingsolubility. ļµ Methods of solubilization. ļµ Addition of co-solvent ļµ pH change method ļµ Reduction of particle size ļµ Temperature change method ļµ Hydro-trophy ļµ Addition of Surfactant ļµ Complexation ļµ Solid dispersion ļµ Polymorphism ļµ Other techniques 6
- 9. Methods of increasingsolubility. ļµ Addition of co-solvent ļµ Substances like weak electrolytes and non-polar molecules are poorly soluble in water. ļµ The solubility of these substances can be enhanced by the addition of water miscible solvents in which the drug has good solubility. This process of improving solubility is called as co-solvency and the solvents used are known as co-solvents. ļµ This technique is mainly used in the formulation of parenterals. ļµ Commonly used co-solvents are Ethanol, Sorbitol, Glycerin, Polyethylene glycol, propylene glycol etc. ļµ E.g. solubility of diazepam can be increased by using 10%ethanol and 40% propylene glycol. 7
- 10. ļµ pH changemethod ļµ Most of drugs are weak acids or weak bases i.e. weak electrolytes. ļµ In aqueous medium they dissociate poorly and un-dissociated portion is insoluble. ļµ So, solubility of the un-dissociated portion is improved by pH control. ļµ For weak acidic drug (Phenytoin, ethosuximide ):- increase pH, solubility is increase. ļµ For weak base drug (caffeine, theophylline ) :- decrease pH, increase 8Methods of increasing solubility.
- 11. ļµ Reduction ofparticle size ļµ Reduction in Particle size improve solubility of drug. ļµ Basically reduction in particle size increase contact surface area of the particle, there ultimately it increase rate of solubility of drug. ļµ Temperature change method ļµ When a mole of solute is dissolved in a large quantity of solvent, then heat is exchanged with surrounding such exchange is termed as Heat of solution. ļµ Most of the substances are endothermic, absorbing heat in the process of For these substances, an increase in temperature results in an increase in solubility. ļµ Exothermic substances give off heat in the process of dissolution. The solubility of substances would decrease with increase in temperature 9Methods of increasing solubility.
- 12. ļµ Hydro-trophy ļµ Hydro-trophyAddition of large amount of a second solute results in an increase in the aqueous solubility of another solute. ļµ Solubilization of Benzoic acid with Sodium benzoate. 10Methods of increasing solubility.
- 13. ļµ Addition ofSurfactant ļµ Surfactants are molecules with well defined polar and non-polar region that allow them to aggregate in solution to form micelles. ļµ Micelles are formed at CMC. ļµ Surfactants act by reducing the surface tension. ļµ Ability of a surfactant solution to dissolve or solubilise water insoluble starts at CMC and with increase in conc. of micelles increases solubility. 11Methods of increasing solubility.
- 14. ļµ Complexation ļµ Forthe Complexation occur both drug and ligand molecule should be able to or accept electrons. ļµ The solubility of compound is the sum of solubility of the compound and its ļµ It is reversible association of a substrate and ligand molecule. ļµ The most common complexing ligands are cyclodextrins, caffeine, urea. ļµ cyclodextrins are unique since they increase the water solubility of poorly soluble by fitting them into the hydrophobic cavity of the cyclodextrins molecule. ļµ These cyclodextrins have the ability to form molecular inclusion complexes with hydrophobic drugs having poor aqueous solubility. 12Methods of increasing solubility.
- 15. ļµ Solid dispersion ļµSolid dispersion technique It is the dispersion of one or more active ingredients in an inert carrier or matrix in solid state prepared by fusion or melting-solvent method. It the dispersion of a drug or drugs in solid diluent or diluents. ļµ Solid dispersions may also be called ā solid state dispersionsā. ļµ Various systems of solid dispersions: ļµ Simple eutectic mixtures ļµ Solid solutions ļµ Glass solution and glass suspension ļµ Amorphous precipitation of drug in crystalline carrier ļµ Compound or complex formation between drug and carrier ļµ Any combination among the above 13Methods of increasing solubility.
- 16. ļµ Polymorphism ļµ Itis the ability of the compound to crystallize as more than one distinct crystalline species with different internal lattice. ļµ Different crystalline forms are called polymorphs. ļµ Polymorphs are of 2 types:- 1. Enatiotropic:- e.g. Sulphur 2. Monotropic:- e.g. Glyceryl stearate ļµ Polymorph differ from each other with respect to their physical property such as 14 ļµ Solubility ļµ Melting point ļµ Density ļµ Hardness ļµ Compression characteristic Methods of increasing solubility.
- 17. ļµ Other techniques ļµSalt formation ļµ Precipitation ļµ Micronization ļµ Nanonization ļµ Supercritical Fluid Recrystallization ļµ Evaporative precipitation into aqueous solution ļµ Use of precipitation inhibitors ļµ Solvent Deposition ļµ Drug derivatization 15Methods of increasing solubility.
- 18. References ļµ The theory& practice of industrial pharmacy by Leon Lachman, Herbert A. Lieberman, Joseph L. kenig, 3rd edition, published by Varghese Publishing house, page no:- 171-196. ļµ Martinās Physical pharmacy & Pharmaceutical science, 6th edition by Patrick J. Sinco, Published by Lippincott williams & wilkins, page no:- 182- 183. 16
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