Different approaches toward the enhancement of drug solubility and/or dissolution rate

Nontraditional methods such as supercritical antisolvent processing and ultrasonic processor rely on physical alterations to enhance drug solubility and dissolution rate. They are advantageous because of their application to a wide variety of drugs and relatively short processing time. Our works show reduced particle size and complexation with these techniques results in the modification of dissolution rate and or solubility. Crystalline form of a drug is preferable because most drugs occur in this form and tend to be stable at this condition. Towards this effort new nanosized crystalline coordination drug polymers are synthesized to enhance drug solubility or dissolution rate. γ-Indomethacin (IMC) is successfully processed with the supercritical antisolvent (SAS) technique. Pure, acicular (needle-like) particles of the α-polymorph are consistently obtained with SAS as the solvent, concentration, temperature and pressures are varied. Controlled changes in process parameters yield significant changes in particle size. Enhanced dissolution profiles are observed with IMC processed with SAS as opposed to the unprocessed IMC. The reduced particle size, as well as the α-polymorphic form of IMC, contributes to the enhanced dissolution rate. Hydroxypropyl-β- cyclodextrin complexation of γ-Indomethacin (IMC) was processed with the supercritical antisolvent (SAS) technique as well. SAS processing resulted in the highest initial dissolution rate of IMC complexed particles compared to both spray drying and the physical mixture. This initial increase in dissolution rate is attributed to the micronization of particles. The addition of the water soluble polymer polyvinylpyrrolidone (PVP) to the IMC complex enhanced the dissolution rate further. Finally, the synthesis of new nanosized crystalline coordination drug polymers is explored. These crystalline coordination drug polymers are composed of the drug molecules coordinated to zinc metal ion as a ligand. The dissolution is controlled mainly by the release of the bridging ligands. These new nanocrystalline CDPs serve as potential for enhanced dissolution.Ph. D.Includes bibliographical referencesIncludes vitaby Princy Ann Abraha