Surfactant-Assisted Wet Granulation-Based Matrix Tablets without Exceptional Additives: Prolonging Systemic Exposure of Model BCS Class II Ketoprofen

Abstract

The present study was aimed to ameliorate the issue of solubility and thereby, bioavailability of ketoprofen, a BCS Class II drug. The sustained release matrix tablets (MT) were prepared using surfactant-assisted wet granulation (SAWG) with 1–5% of different surfactants. The tablet characteristics were within the compendial limits. The selected sustained release-compliant matrix tablet formulation containing granules prepared using 3% Soluplus® (MT2) released the drug by swelling-erosion. In human volunteers, MT2 attained the maximum plasma concentration (C_max) of 5.72µg /ml ± 0.30 h, time to C_max (T_max) of 5.56 ± 0.30 h and maintained the plasma concentration above its minimum effective concentration (MEC), 0.7 µg.ml⁻¹ till 24h. A control formulation, prepared from granules without surfactant (MT16), promptly attained C_max of 9.62 ± 0.76 µg/ml within 1h but rapidly declined to below MEC in 8h. Area under the curve from initial point to infinity (AUC_0-∞) of MT2 (78.65 ± 7.64 µg.h.ml⁻¹) was 2.29 folds higher than 34.39 ± 3.06 µg.h.ml⁻¹ of MT16. With decreased C_max, increased AUC_0-∞, delayed T_max and retained ketoprofen concentration above MEC for longer time, MT2 corresponded with the in-vitro sustained drug release characteristic. There is a likelihood of administration of once-a-day single dose of MT2 without plasma fluctuations, expected from two doses of MT16. SAWG helped developing a swellable-erodible sustained release matrix tablet formulation of ketoprofen with the desired biopharmaceutical and pharmacokinetics properties, merely by addition of Soluplus® in granules and without incorporation of any special ingredients or the major manipulation of the formulative ingredients in the formulation.

Graphical Abstract