Objective: Telmisartan (TEL), commonly used antihypertensive, is poorly soluble in water and has limited and variable bioavailability. Commercially, TEL is available as a single drug and in combination with hydrochlorothiazide (HYZ). Researchers have developed cocrystals of TEL with coformers, namely, oxalic acid, glutaric acid, and saccharin. An attempt was made to prepare the cocrystals of TEL with HYZ, an active pharmaceutical ingredient (API) itself so that both the APIs are available in a single tablet. The present study was aimed at enhancement in solubility of TEL by formation of its cocrystals. Methods: The cocrystals of TEL with HYZ, in different stoichiometric ratios (1:0.5, 1:1, and 1:2), were prepared by solvent coevaporation and liquid-assisted grinding methods. The cocrystals, consisting of TEL:HYZ (in 1:0.5 ratio and 1:1 ratio), depicted maximum yield, drug content, saturation solubility, and flow properties. These cocrystals were characterized by X-ray analysis, infrared spectroscopy, and thermal analysis. Results: The crystal structure of TEL-HYX revealed that it was a cocrystal, since no proton was transferred between the TEL and HYZ molecules. It was predicted that two molecules are associated through a hydrogen bond between an acidic group of TEL and sulfonamido group of HYZ. The cocrystallization improved the solubility of TEL 7 times. In vitro release rate of tablets of cocrystals was higher than that of marketed TEL tablets. HYZ has a potential to form the cocrystals of TEL. Conclusion: The objective of improvement in the solubility of TEL was successfully achieved by the formation of cocrystals of TEL: HYZ.
Objective: Co-crystal is defined as a crystalline complex of two or more neutral molecules bound together primarily by hydrogen bonding or other non-covalent interactions. The pharmaceutical co-crystal involves crystal lattice arrangement between an Active Pharmaceutical Ingredient (API) with another pharmaceutically acceptable molecule. Co-crystals of API are preferred since they depict improved solubility, dissolution, stability, compressibility in comparison with API. Ibuprofen lysine (IL), frequently used analgesic and the anti-inflammatory drug has poor aqueous solubility and compressibility. This work shows the feasibility and optimal conditions for the preparation of co-crystals of ibuprofen lysine using Polyvivylpyrrolidone K25 (PK 25) and Polyvivylpyrrolidone K30 (PK 30) as co-formers. Methods: In this study, we prepared and studied the solubility, drug content, flow properties, physical stability of novel co-crystal, consisting of IL and PK 25/PK 30. The co-crystal IL: PK 30 (at a molar ratio of 0.29:0.5) and IL: PK 25 (at a molar ratio of 0.58:1) were characterized by X-ray analysis, infrared spectroscopy and thermal analysis. Furthermore, the tablet formulations of the co-crystals were subjected to in vitro dissolution and in vivo analgesic activity, with the goal of comparing the co-crystals with IL and the marketed tablet of ibuprofen (Brufen®) respectively. Results: The IL: PK co-crystals demonstrated superior solubility and the dissolution properties over IL. The compression properties of the co-crystals were similar to IL. The co-crystals exhibited higher analgesic activity than the marketed tablet. Conclusion: The results indicated the use of PK 25 and PK 30 as safe and promising co-crystal formers.
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