Stable Co-crystals of Glipizide with Enhanced Dissolution Profiles: Preparation and Characterization

Abstract

Present study deciphers preparation of co-crystals of lipophilic glipizide by using four different acids, oxalic, malonic, stearic, and benzoic acids, in order to achieve enhanced solubility and dissolution along with stability. All co-crystals were prepared by dissolving drug and individual acids in the ratio of 1:0.5 in acetonitrile at 60-70°C for 15 min, followed by cooling at room temperature for 24 h. FT-IR spectroscopy revealed no molecular interaction between acids and drug as the internal structure and their geometric configurations remain unchanged. Differential scanning calorimetry revealed closer melting points of raw glipizide and its co-crystals, which speculates absence of difference in crystallinity as well as intermolecular bonding of the co-crystals and drug. PXRD further revealed that all the co-crystals were having similar crystallinity as that of raw glipizide except glipizide-malonic acid co-crystals. This minor difference in the relative intensities of some of the diffraction peaks could be attributed to the crystal habit or crystal size modification. SEM revealed difference in the crystal morphology for all the co-crystals. Micromeritic, solubility, dissolution, and stability data revealed that among all the prepared co-crystals, glipizide-stearic acid co-crystals were found superior. Hence, it was concluded that glipizide-stearic acid co-crystals could offer an improved drug design strategy to overcome dissolution and bioavailability related challenges associated with lipophilic glipizide.

Use of Glutaric Acid to Improve the Solubility and Dissolution Profile of Glipizide Through Pharmaceutical Cocrystallization

“…Similarly, in the case of GPZ-GLU (1 : 2) cocrystals, crystalline peaks were present indicating the formation of cocrystals. All the crystalline peaks of glipizide were seen in formulated cocrystals as supported by a previous study (22). PXRD pattern of pure components and fabricated GPZ-GLU cocrystals has given in Figure 2.…”

The Physico-Chemical Properties of Glipizide: New Findings

“…Therefore, the attribution of the glipizide DSC peak to a simple melting process is not correct [ 10 , 11 , 12 ]. The calorimetric peak is undoubtedly triggered by a decomposition process, which involves a gaseous product evolution and then a mass loss under the peak.…”

“…According to the studies published in the scientific literature, GPZ melts at a temperature higher than 200 °C, and different melting temperatures have been reported [ 10 , 11 , 12 ]. The crystal structure of glipizide has been recently addressed by single-crystal X-ray diffraction data [ 13 ].…”

Design and Preparation of Zaltoprofen-Nicotinamide Pharmaceutical Cocrystals via Liquid Assisted Grinding Method

“…The 5 ml of samples were withdrawn after specified time interval and analyzed by UV spectrophotometer at 243 nm. 26,27 The dissolution profiles of ZFN and cocrystals were compared by similarity factor according to following equation Where f 2 is similarity factor, n is the number of observations, R t is the average percentage drug dissolved from reference formulation and T t is the average percentage drug dissolved from test formulation. An f 2 value above 50 indicates similarity in two profiles.…”

“…Similar studies were reported for cocrystals of glipizide, aceclofenac etc. 26,30 Based on the results, ZFN:nicotinamide cocrystals were further subjected to evaluation and validated.…”