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

• Published in: International journal of biological macromolecules 2012-04, Vol.50 (3), p.565-572
• Main Authors: Bain, Mrinal Kanti, Bhowmick, Biplab, Maity, Dipanwita, Mondal, Dibyendu, Mollick, Md. Masud Rahaman, Paul, Bijan Kumar, Bhowmik, Manas, Rana, Dipak, Chattopadhyay, Dipankar
• Format: Article
• Language: English
• Subjects: alcohols; Average molecular weight; Drug Carriers - chemistry; drugs; Fourier transform infrared spectroscopy; gel strength; gelatinization temperature; Gelation temperature; Gels; in vitro studies; Ketorolac Tromethamine - chemistry; Kinetics; methylcellulose; Methylcellulose - chemistry; Models, Molecular; Molecular Conformation; Molecular Weight; Ophthalmic Solutions - chemistry; Poly(vinyl alcohol); polyvinyl alcohol; Polyvinyl Alcohol - chemistry; Rheology; rheometry; sodium chloride; Sustained release of drug; Temperature; viscometry; Viscosity
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2012.01.025

► Effect of molecular weight of PVA on the gelation temperature of MC. ► The gelation temperature was measured by TTM (test tube tilting method), UV–vis spectroscopy, viscometer and rheometer. ► Interaction between PVA and MC was established by FT-IR. ► Drug–PVA interaction was established theoretically (GAUSSIAN 03W software package). ► Effect of molecular weight of PVA on the drug release kinetics of ketorolac tromethamine (KT) from MC–PVA based formulations and maximum drug release time of 8h was obtained. 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 9×103 to 1.3×105 and this was due to the higher viscosity, better gel strength and greater interactions between the drug and PVA molecules in case of PVA (1.3×105) compared to PVA (9×103). 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.