Lebo, David; Canney, Daniel J.; Abou-Gharbia, Magid; Borenstein, Michael R.; Bi, Yunxia (Vivian) (Temple University. Libraries, 2012)
      It is a well reported fact that large number of drugs coming of the drug discovery pipeline show poor aqueous solubility. Eutectic mixture formation of poorly soluble drugs with hydrophilic carriers has been used to enhance the dissolution rate of such poorly soluble drugs. Eutectic mixtures are solid dispersions where the drug and the carrier are both in crystalline form. The eutectic mixture has a lower melting point than either component. Eutectic mixtures are thermodynamically stable systems. The feasibility of developing a dosage form from an eutectic mixture depends on the phase diagram. Poloxamers are polyoxyethylene-polyoxypropylene-polyoxyethylene block polymers which have surfactant properties. Phase diagram construction and dissolution rate enhancement mechanism in crystalline poloxamer based eutectics has not been reported in pharmaceutical literature. This thesis involved the detailed study of poloxamer 188 (PL 188) based eutectic mixtures. Eutectic mixture formation between PL 188 and drugs with diverse physicochemical properties was proved. Accurate experimental phase diagrams were constructed using solid state characterization techniques and theoretical phase diagrams were predicted using Lacoulonche et al's model. The model was accurate in predicting the phase diagrams of most drugs. Discrepancies were observed in case of drugs showing hydrogen bonding interactions with PL 188. This was confirmed by a blue shift of the carbonyl band using fourier transform infra-red spectroscopy. A unique novel graphical method for estimating the accurate eutectic composition of PL 188 based eutectics with about 50 mg of drug was devised. PL 188 was effective in improving the dissolution rate of a poorly soluble drug ibuprofen in pH 1, 4.5 and 7.2. For the first time a detailed study establishing melting point depression due to eutectic formation as a reason for dissolution enhancement was described. Contrary to expectation it was realized that maximum dissolution rate enhancement takes place at drug ratios well above the eutectic composition. The utility of PL 188 as a eutectic mixture carrier was shown by comparing ketoprofen PL 188 eutectic mixtures with ketoprofen soluplus (glass solutions) and ketoprofen urea solid dispersions(amorphous precipitation in crystalline carrier). The ketoprofen PL 188 eutectic mixtures had better dissolution enhancing effect and physical stability.