Abstract
Purpose: To design controlled release ketorolac tromethamol (KT) matrix tablets for increased drug bioavailability.
Methods: Waxes (Compritol® ATO 888, Precirol® ATO 5 and stearic acid - SA) and polymers (hydroxypropyl methylcellulose - HPMC and xanthan gum - XG) were used in the preparation of the matrix tablets at various excipient concentrations for controlled drug delivery. The physical properties of the formulations were determined. Drug release profiles from the tablets were obtained and their drug release mechanisms were characterized by kinetic modeling. Analytical quantification method of KT in dissolution media was also validated by certain performance criteria.
Results: KT matrix tablets prepared individually with Compritol and HPMC at 30 and 40 % concentrations, respectively, displayed the best tablet compression properties. The tablets prepared with HPMC and XG displayed slower drug release profiles compared to the tablets prepared with waxes in general (p < 0.05). KT release increased with increase in pH since it is a weak acid (p < 0.05). Statistically insignificant difference was observed among all the tablets prepared with HPMC and XG in water (p > 0.05). However, drug release from the tablets containing 40 % XG was faster than tablets prepared with HPMC (30 and 40 %) and XG (30 %) at pH 7.2 (p < 0.05). Drug release mechanisms from the tablets prepared with wax and polymers were non-Fickian, indicating coupled diffusion/erosion and diffusion/polymer relaxation, respectively.
Conclusion: KT matrix tablets have been successfully formulated by direct compression method. The findings demonstrate that both the desired physical characteristics and drug release profiles were obtained for matrix tablets prepared with HPMC.
Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, Beyazit, Istanbul 34116, Turkey
http://dx.doi.org/10.4314/tjpr.v15i12.3