Approaches to Improving Aqueous Solubility PDF

Approaches to the improvement of aqueous solubility  Strongly ionized materials are likely to be freely soluble in water.  weak acids and bases should be adequately soluble at favourable pHs.  The concentration of any material is not close to its limit of solubility (cooling / evapor...

Approaches to the improvement of aqueous solubility  Strongly ionized materials are likely to be freely soluble in water.  weak acids and bases should be adequately soluble at favourable pHs.  The concentration of any material is not close to its limit of solubility (cooling / evaporation).  1. Cosolvency  The solubility of a weak electrolyte ornon-polar compound in water can beachieved by the addition of another solvent that isboth miscible with water and in which the compoundis also soluble.  increase the solubility of a drug.  The solubility in this mixed system is greater than can be predicted from the material's solubility in each individual solvent.  1. Cosolvency  Choice of cosolvent (toxicity and irritancy), oral / parenteral.  Ideally, suitable blends should possess values of dielectric constant between 25 and 80.  Water/ethanol blend.  Sorbitol, glycerol, propylene glycol and syrup.  co-trimoxazole: PG / water  Paracetamol: alcohol / PG / syrup / water.  2. pH control  A large number of drugs are either weak acids or weak bases.  Henderson-Hasselbalch equation (pKa / solubility of its unionized species / pH).  weak base > lowering pH  weak acid > increase in pH  The chosen pH does not conflict with other product requirements (chemical stability).  2. pH control  A large number of drugs are either weak acids or weak bases.  Henderson-Hasselbalch equation (pKa / solubility of its unionized species / pH).  weak base > lowering pH  weak acid > increase in pH  The chosen pH does not conflict with other product requirements (chemical stability).  3. Solubilization  Addition of a surface-active agent (SAA) (nontoxic, non irritant).  SAA form different types of micelles, ranging from simple spherical structures to more complex liposomes and liquid crystals.  In aqueous systems, non-polar molecules will dissolve in the interior of the micelle, which consists of the lipophilic hydrocarbon moiety.  3. Solubilization  The amount of surfactant must be carefully controlled (cost, toxicity).  Excessive amounts may also reduce the bioavailability of a drug if it is strongly adsorbed within the micelle.  3. Solubilization  It is also important to ensure that the formulation chosen does not lie too close to a phase boundary (depend on the storage temperature).  In general the degree of solubilization of a drug increases as the temperature increases.  3. Solubilization  E.g. 1: solubilization of fat-soluble vitamins such as phytomenadione using polysorbates.  3. Solubilization  E.g. 2: Iodine + macrogol ethers (PEG) = iodophores.  Improve chemical stability, reduce loss of active agent due to sublimation, less corrosion of surgical instruments and, in some cases, enhanced activity.  3. Solubilization  E.g. 3: phenolic compounds (cresol / chloroxylenol) + soaps = micelle.  Lysol contains50% cresol in an aqueous system by the use ofthe potassium soaps of oleic, linoleic and linolenicacids.