Evaluation of lipid-based drug delivery system [phytosolve] on oral bioavailability of dibudipine

The objective of present study was to evaluate pharmacokinetic parameters of dibudipine Phytosolve after oral administration in rats. The solubility test was carried out to select suitable oily solvent for dibudipine. Phytosolve formulation was prepared with a medium chain triglyceride [MCT] oil [20%], soybean phospholipids [5%] and a 70% fructose solution [75%]. The effect of polyol content on the mean globule size of Phytosolve formulation was studied. The optimized formulation was evaluated for robustness toward dilution, transparency, droplet size, zeta potential and transmission electron microscopic analysis. The Phytosolve of dibudipine with an average droplet size of 142.3 +/- 4.3 nm and surface charge -18.36 +/- 0.37 mv was administered orally to rats. The average relative bioavalabilities of dibudipine in the plasma with Phytosolve were 170.4% and 211.2% as compared to the oily solution and aqueous suspension respectively. So this formulation could be offered as a useful technique to improve the oral delivery of the poorly water soluble drugs such as dibudipine

Evaluation of antinociceptive effect of pregabalin in mice and its combination with tramadol using tail flick test

The development of combination therapy is a coherent approach in severe pain treatment. The present study investigated the antinociceptive effect of pregabalin alone and in combination with tramadol in acute pain modeling. Therefore, three groups of male mice received either pregabalin [1 to 400 mg/Kg], tramadol [10 to 80 mg/Kg] or their combination intraperitoneally. Then latency time, maximum possible effect [%MPE] and area under curve [AUC] were calculated in tail flick test. The antinociceptive indexes were significantly increased in10, 100 and 200 mg/kg of pregabalin while tramadol showed dose-dependent antinociception [effective dose 50% was 54 to 79 mg/Kg]. The antinociceptive effect of 100 mg/Kg of pregabalin [%MPE = 35 +/- 4%] was similar to that of 50 mg/Kg of tramadol. The combination of non-analgesic doses [10 mg/Kg] of tramadol and pregabalin did not increase%MPE and AUC, but the co-administration of 30 mg/Kg of tramadol with pregabalin [10 mg/Kg] increased all antinociceptive indexes significantly compared to the controls and with each drug alone. In conclusion, pregabalin showed a comparable antinociceptive effect to tramadol. The increase in analgesic effect was observed after the combination of low analgesic doses of tramadol with pregabalin, while the combination of non-analgesic doses of each drug reversed the interaction to antagonism. Therefore to increase the analgesic effect in pain management, more attention should be paid to respecting right proportion of drug combination. Further studies that specify the mechanism[s] and statement of interaction are needed to expand these findings to clinical applications