Enhancement of the dissolution profile of Tenoxicam by a solid dispersion technique and its analytical evaluation using HPLC.
The aim of the present study was to improve the dissolution, and therefore the bioavailability, of poorly water-soluble tenoxicam. Solid dispersions consisting of tenoxicam with two different types of polymers were prepared. The first type were PVP(30) and β-cyclodextrin and the second type were two superdisintegrants, explotab and croscarmellose sodium. A solid dispersion with an explotab ratio of 1:1 (F(8)) had the best dissolution profile compared to all of the prepared solid dispersions as well as the pure drug, which was then formulated into tablets (T(2)F(8)). T(2)F(8) had far better dissolution than commercial tablets, releasing only 28.3% of the drug, while T(2)F(8) exhibited 96.5% drug release in 20 min. T(2)F(8) was subjected to analytical validation as well as stability studies. The formulation was found to be stable after storage at 40°C for one month, 40°C and 75% relative humidity (40°C/75% RH) for one month, and 60°C for 15 days; this was confirmed by the absence of degraded product prepared in the laboratory by refluxing the drug with 1 N NaOH for 15 min. Infrared (IR) spectroscopy and differential scanning calorimetry (DSC) were performed on T(2)F(8) to identify physicochemical interactions between the drug and carrier, hence its effect on dissolution. A simple and rapid HPLC method was also developed to determine tenoxicam in human plasma and was then used in a pharmacokinetic study. Plasma samples were analyzed on a C(18) column with a mobile phase of 0.02 M sodium acetate:acetonitrile: methanol (7:2.5:0.5, v/v/v) and UV detection at 375 nm. The linear range of the plasma concentration was 1-16 μg/mL with a detection limit of 158 ng/mL. Within-day and between-day precision expressed as the relative standard deviation was less than 2%. The proposed method was successfully used in a bioequivalence study in healthy volunteers and mean pharmacokinetic parameters were calculated.