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Effect of PVA on the gel temperature of MC and release kinetics of KT from MC based ophthalmic formulations.

International journal of biological macromolecules (2012-02-04)
Mrinal Kanti Bain, Biplab Bhowmick, Dipanwita Maity, Dibyendu Mondal, Md Masud Rahaman Mollick, Bijan Kumar Paul, Manas Bhowmik, Dipak Rana, Dipankar Chattopadhyay
RESUMEN

The effect of molecular weight of poly(vinyl alcohol) (PVA) and sodium chloride on the gelation temperature of methylcellulose (MC) was studied with the objective to develop a MC based formulation for sustained delivery of ketorolac tromethamine a model ophthalmic drug. Pure MC showed sol-gel transition at 61.2 °C. In order to reduce the gelation temperature of MC and to increase the drug release time, PVA was used. Different techniques such as test tube tilting method, UV-vis spectroscopy, viscometry and rheometry were used to measure gelation temperature of all the binary combinations of MC and PVA. It was observed that the gelation temperature of MC was reduced with the addition of 4% PVA and also the extent of reduction of the gelation temperature of MC was dependent on the molecular weight of PVA. The strong interactions between MC and PVA molecules were established using Fourier transform infrared spectroscopy. To study the in vitro drug release properties of the MC-PVA binary combinations, 6% sodium chloride was used to reduce the gelation temperature further up to physiological temperature. It was observed that the drug release time increased from 5 to 8h with the increase of molecular weight of PVA from 9×10(3) to 1.3×10(5) and this was due to the higher viscosity, better gel strength and greater interactions between the drug and PVA molecules in case of PVA (1.3×10(5)) compared to PVA (9×10(3)). In order to have an idea about the nature of interactions between the functional moieties of the drug and the polymer unit of PVA, a theoretical study was carried out.

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Supelco
Ketorolac Tromethamine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Ketorolac tris salt, ≥99%, crystalline
Ketorolac trometamol, European Pharmacopoeia (EP) Reference Standard
Ketorolac trometamol for peak identification, European Pharmacopoeia (EP) Reference Standard