SOLUBILITY AND DRUG SOLUBILIZATION
2.1 SOLUBILITY Solubility is commonly related to the bioavailability of the compound of interest,particularly for poorly soluble compounds. Administration of a drug in any dosage form, except solution involves a dissolution step.It is necessary that the drug present in the dissolved state at the site of absorption then only it can be absorbed. It must be soluble in and transported by the body fluids, transverse the required biologic membrane barriers, escape widespread distribution to unnecessary areas, endure metabolic attack, penetrate inadequate concentration to the sites of action and interact in a specific fashion, causing an alteration of cellular function.
2.2 DRUG SOLUBILISATION [14][15] Solubility …show more content…
Pharmacopoeia fall into the poorly water-soluble or water-insoluble categories.It was reported a couple of decades ago that more than 41% of the failures in new drug development is attributed to poor biopharmaceutical properties, including water insolubility.Water insolubility can postpone or totally halt new drug developmentand can prevent muchessential reformulation of currently marketed products.
2.3 THREE MAJOR FACTORS OF SOLUBILITY OF DRUG [16][17]
• The entropy of mixing favours miscibility of all components.
• The difference between the sum of the drug-drug (DD) and water-water (WW) interactions on the one hand and the drug-water interactions on the other hand. The difference is correlated to the activity-coefficient of the drug in water w by the equation as given by:
RT In w =DD + WW -2DW . If DD + WW -2DW>0
(usual case of non-electrolytes in water), there will be less than complete mixing and the drug will have a finite solubility in water.The greater difference between in the adhesive and cohesive interactions, lower the …show more content…
2.4.2Excess Solute Addition Method [19][20] The equilibrium solubility of drug candidate is obtained by the equilibrating an excess of material in the vial through solvent. The vial is then shaken at constant temperature and the amount of drug is determined periodically by analysis of the supernatant until the equilibrium is achieved. Solubility determination of organic molecules having very low solubilities is hampered by such problems,slow equilibration during measurement, influence of impurities, and inherent heterogeneity in the energetic content of crystalline solid. Higuchi described methods for determining solubility of barely aqueous soluble organic solids (solubility less than 0.2%). The three methods
2.1 SOLUBILITY Solubility is commonly related to the bioavailability of the compound of interest,particularly for poorly soluble compounds. Administration of a drug in any dosage form, except solution involves a dissolution step.It is necessary that the drug present in the dissolved state at the site of absorption then only it can be absorbed. It must be soluble in and transported by the body fluids, transverse the required biologic membrane barriers, escape widespread distribution to unnecessary areas, endure metabolic attack, penetrate inadequate concentration to the sites of action and interact in a specific fashion, causing an alteration of cellular function.
2.2 DRUG SOLUBILISATION [14][15] Solubility …show more content…
Pharmacopoeia fall into the poorly water-soluble or water-insoluble categories.It was reported a couple of decades ago that more than 41% of the failures in new drug development is attributed to poor biopharmaceutical properties, including water insolubility.Water insolubility can postpone or totally halt new drug developmentand can prevent muchessential reformulation of currently marketed products.
2.3 THREE MAJOR FACTORS OF SOLUBILITY OF DRUG [16][17]
• The entropy of mixing favours miscibility of all components.
• The difference between the sum of the drug-drug (DD) and water-water (WW) interactions on the one hand and the drug-water interactions on the other hand. The difference is correlated to the activity-coefficient of the drug in water w by the equation as given by:
RT In w =DD + WW -2DW . If DD + WW -2DW>0
(usual case of non-electrolytes in water), there will be less than complete mixing and the drug will have a finite solubility in water.The greater difference between in the adhesive and cohesive interactions, lower the …show more content…
2.4.2Excess Solute Addition Method [19][20] The equilibrium solubility of drug candidate is obtained by the equilibrating an excess of material in the vial through solvent. The vial is then shaken at constant temperature and the amount of drug is determined periodically by analysis of the supernatant until the equilibrium is achieved. Solubility determination of organic molecules having very low solubilities is hampered by such problems,slow equilibration during measurement, influence of impurities, and inherent heterogeneity in the energetic content of crystalline solid. Higuchi described methods for determining solubility of barely aqueous soluble organic solids (solubility less than 0.2%). The three methods