Formulation Design and Characterization of an Elementary Osmotic Pump Tablet of Flurbiprofen

Kunal N. Patel; Tejal A. Mehta

doi:10.5731/pdajpst.2014.00984

Abstract

Elementary osmotic pumps are well known for delivering moderately soluble drugs at a zero-order rate. The objective of the present study was to develop elementary osmotic pump tablets containing Flurbiprofen using an inclusion complex. Formation of complex was confirmed by Differential Scanning Calorimetry and Fourier Transform Infrared Spectroscopy. A 3² factorial design was applied systematically; the amount of osmotic agent (X₁) and size of delivery orifice (X₂) were selected as independent variables. Batches were prepared by the direct compression method and evaluated for percent cumulative drug release (%CDR) at 9 h as dependent variables. The amount of osmotic agent and size of the delivery orifice had a significant effect on %CDR. The results of multiple linear regression analysis revealed that elementary osmotic pump tablets should be prepared using an optimum concentration of osmotic agent and size of delivery orifice to achieve a zero-order drug release. Contour plots as well as response surface plots were constructed to show the effects of X₁ and X₂ on %CDR. A model was validated for accurate prediction of %CDR by performing checkpoint analysis. The computer optimization process, contour plots, and response surface plots were predicted at the concentration of independent variables X₁ and X₂ (78.38 mg and 0.99 mm, respectively), for maximized response. The drug release from the developed formulation was found to be independent of pH and agitational intensity. The above optimized batch was also evaluated by different pharmacokinetic models like zero-order, first-order, Higuchi, Korsmeyer Peppas, and Hixson Crowell models. Stability study of the optimized batch was conducted at accelerated conditions for 6 months, and was found stable. This study strongly indicates application of osmotic tablets of Flurbiprofen for the treatment of rheumatoid arthritis, as well as osteoarthritis.

LAY ABSTRACT: The aim of this study was to develop an elementary osmotic pump tablet of Flurbiprofen and to deliver the drug at a zero-order rate. Elementary osmotic pumps are well known for delivering moderately soluble drugs at a zero-order rate. Elementary osmotic pump tablets containing an inclusion complex of Flurbiprofen was prepared by the direct compression method. The amount of osmotic agent and size of delivery orifice were selected as independent variables. Percent cumulative drug release at 9 h was evaluated for all batches, and it was found that amount of osmotic agent and size of delivery orifice had a significant effect on percent cumulative drug release. The drug release from the developed formulation was found to be independent of pH and agitational intensity. It was also observed that the optimized formulation followed zero-order kinetics and was stable for 6 months at accelerated conditions.

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