Development and Evaluation of Matrix Controlled Release Formulations of Ketoprofen

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Date
2010-10
Authors
KHAN, JIYAUDDIN
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Abstract
The present study was conducted to investigate the suitability of various hydrophilic and hydrophobic polymers or their combination, as matrix forming materials for the development of a controlled release tablet formulation of ketoprofen with in vitro and in vivo performance comparable to that of the marketed preparation Apo-Keto SR® tablets. In this regard a number of matrix controlled release formulations of ketoprofen tablets were developed using different hydrophilic, hydrophobic and mixtures of both polymeric materials. All the formulations were prepared by direct compression method. Their in vitro dissolution profiles were compared to that of the commercially available reference product Apo-Keto SR® tablet. Similarity factor (f2), values between test formulations and reference product were also calculated to select the optimum formulation. Out of all the matrix formulations studied, tablets conwining 20% HPC (GXF) as matrix former showed comparable dissolution profile to that of the reference. The f2 value between reference and matrix tablets with 20% HPC (GXF) was 78.0%, and hence it was selected for further investigation. The drug release from reference and matrix with 20% HPC (GXF) formulation was governed by both diffusion and erosion (anomalous) mechanism as per Korsmeyer-Peppas equation. Moreover, the optimized formulation was found to be stable for a period of 12 months upon storage at 25°C of room temperature for a long term of stability. A HPLC UV method was developed and validated for the determination of ketoprofen in human plasma. An in vivo study was then conducted in 6 healthy human volunteers to compare the performance of the test formulation with the commercial reference product. The study was performed according to a single dose, randomized, xxxii 2-treatment, 2-sequence, 2-period crossover study design. The statistical results showed that there was no significant difference between pharmacokinetic parameters of Tmax, Cmax, and AUC0-oo of reference product and test formulation. The 90% confidence intervals of the mean values for the test/reference ratios were 96.9-107.0% for AUC0-oo and 99.6-104.6% for Cmax,respectively. Hence, the rate and extent of absorption of test formulation were comparable to the reference product. In conclusion, a stable matrix controlled release tablets of ketoprofen was successfully developed, which exhibited similar in vitro dissolution profile as well as in vivo performance as that of marketed reference tablet of Apo-Keto SR®
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Ketoprofen
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