Ibuprofen microspheres were prepared from the racemate, (+)-S and (-)-R enantiomers using waxes such as ceresine and glyceryl stearate and stereospecifically characterized. The method of preparation of the microspheres was a hydrophobic congealable disperse phase encapsulation process and variables such as particle size, wax type, enantiomeric form were evaluated. Dissolution studies were carried out by a modified USP type II method and the samples were analysed by a stereospecific HPLC assay using S-(-)-1(1) naphthylethylamine as the derivatizing agent and fenoprofen as the internal standard. The mean particle sizes of (+)-S and (-)-R enantiomers determined by microscopy/image analysis were 64 and 99 microns respectively while that of the racemate was 48 microns. Differential Scanning Calorimetry (DSC) of ibuprofen and the enantiomers showed endothermic peaks at 72 and 55 degrees C respectively. Thermograms of the physical mixture and microspheres did not show the characteristic ibuprofen peak, indicating a change in crystallinity of the drug. Powder X-ray diffraction patterns of the enantiomers and racemic ibuprofen were found to be dissimilar indicating different crystal properties. The X-ray patterns for the microspheres did not show the characteristic peaks for the drug indicating that ibuprofen may be in solid solution with the waxes. Scanning electron micrographs of the microspheres showed a generally smooth and spongy appearance for the microspheres made of compritol and glyceryl stearate. Microspheres made from the paraffin waxes had rough and hard surface characteristics consistent with the higher melting point of the waxes. Ceresine microspheres made with the enantiomers had a rougher and more porous surface compared to the microspheres made with racemic ibuprofen. Stereospecific release of the recemate from the formulations was found to be sustained (T25 of 4 h), while release from the enantiomers was less sustained (T50 of 2 h). From the S:R ratios and statistical analysis of the data, the release of the enantiomers of ibuprofen from the formulations containing the racemate was found to be non-stereoselective.

The purpose of this research was to evaluate the stereospecific interaction of ibuprofen with chiral excipients such as hydroxypropyl-beta-cyclodextrin (HPCD), tartaric acid, sucrose, hydroxypropylmethylcellulose (HPMC), methylcellulose (MC), and a nonchiral excipient, citric acid. Coprecipitates of ibuprofen were prepared in molar ratios ranging between 1:0.5 and 1:10 by a solvent evaporation method and characterized using x-ray diffraction, Fourier-transform infrared (FTIR) spectroscopy, and dissolution testing. Phase solubility studies of ibuprofen were carried out by adding excess amount of ibuprofen to aqueous excipient solutions of varying concentrations. Interaction was studied in suspensions of ibuprofen with HPMC, MC, and sucrose stored at room temperature and 60 degrees C for 12 weeks. Solubility of ibuprofen in HPCD solutions increased 10-fold, whereas solubility decreased in the tartaric and citric acid solutions, a result of decreased pH with increased amount of the acids in which ibuprofen (pKa 4.8) is less soluble. Phase solubility diagrams of ibuprofen in aqueous HPCD, citric acid, and tartaric acid solutions showed no stereospecific differences in solubility of the two enantiomers. X-ray diffraction studies showed that ibuprofen exists in a crystalline form at low ibuprofen-to-excipient ratios, whereas at the higher ratios, it exists in an amorphous form. FTIR spectroscopy for HPCD coprecipitates showed a shift of the carbonyl stretching band of ibuprofen to a higher wavelength with a markedly decreased intensity, probably because of a breakdown in the intermolecular hydrogen bonding with ibuprofen and restriction of the drug molecule in the HPCD cavity, respectively. Dissolution profiles of the coprecipitates demonstrated higher dissolution rates than those of pure ibuprofen. The presence of chiral excipients did not appear to cause stereoselective release of the drug from the coprecipitates and the suspensions.

The purpose of this research was to evaluate the stereospecific interaction of ibuprofen with chiral excipients such as hydroxypropyl-beta-cyclodextrin (HPCD), tartaric acid, sucrose, hydroxypropylmethylcellulose (HPMC), methylcellulose (MC), and a nonchiral excipient, citric acid. Coprecipitates of ibuprofen were prepared in molar ratios ranging between 1:0.5 and 1:10 by a solvent evaporation method and characterized using x-ray diffraction, Fourier-transform infrared (FTIR) spectroscopy, and dissolution testing. Phase solubility studies of ibuprofen were carried out by adding excess amount of ibuprofen to aqueous excipient solutions of varying concentrations. Interaction was studied in suspensions of ibuprofen with HPMC, MC, and sucrose stored at room temperature and 60 degrees C for 12 weeks. Solubility of ibuprofen in HPCD solutions increased 10-fold, whereas solubility decreased in the tartaric and citric acid solutions, a result of decreased pH with increased amount of the acids in which ibuprofen (pKa 4.8) is less soluble. Phase solubility diagrams of ibuprofen in aqueous HPCD, citric acid, and tartaric acid solutions showed no stereospecific differences in solubility of the two enantiomers. X-ray diffraction studies showed that ibuprofen exists in a crystalline form at low ibuprofen-to-excipient ratios, whereas at the higher ratios, it exists in an amorphous form. FTIR spectroscopy for HPCD coprecipitates showed a shift of the carbonyl stretching band of ibuprofen to a higher wavelength with a markedly decreased intensity, probably because of a breakdown in the intermolecular hydrogen bonding with ibuprofen and restriction of the drug molecule in the HPCD cavity, respectively. Dissolution profiles of the coprecipitates demonstrated higher dissolution rates than those of pure ibuprofen. The presence of chiral excipients did not appear to cause stereoselective release of the drug from the coprecipitates and the suspensions.

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