P. Ravi Prakash

Bortezomib is formulated as the solid lipid nanoparticle (SLN) system with the use of a 3-factor, 3-level Box–Behnken design, by hot homogenization followed by an ultra sonication method. Trimyristin (Dynasan-114), tripalmitin (Dynasan116) and tristearin (Dynasan-118) were used as lipids and based on the results from the initial studies tripalmitin (Dynasan116) was selected as the lipid for the further studies along with phosphate dylcholine as surfactant and Poloxamer 188 as stabilizer. The optimized formulation (F1) was obtained with minimum particle size (204 nm), maximum entrapment efficiency (70.24) and drug loading (21.24). In vitro release studies showed that maximum cumulative drug release was obtained for F1 (99.74%). The optimized formulation Bortezomib followed zero-order release kinetics with a strong correlation coefficient (R2= 0.9994). The pharmacokinetic studies in rabbits demonstrated that SLN formulation could be used for increasing the oral bioavailability of the drug for more than 2 fold when compared with pure drug. SLNs of Bortezomib were successfully developed to yield an optimized formulation with lowest particle size and highest entrapment efficiency that could sustain the release of drug. Key words: Bortezomib, SLN, Cancer, Tripalmitin, Box-Behnken design, Pharmacokinetic studies.

Atorvastatin calcium is a HMG-CoA reductase inhibitor used in the treatment of hyperlipidaemia. It has oral bioavailability of less than 12%. It also undergoes high first pass metabolism. The objective of the present work was to formulate, optimize and in vivo evaluation of the potential novel proniosomal gel containing atorvastatin for transdermal delivery. On the basis of the preliminary trials a 3-factor, 3-level Box–Behnken design was employed to study the effect of Cholesterol, soya lecithin and Span 60 independent variable on dependent variables (particle size and % entrapment efficiency). Atorvastatin optimized proniosomal formulation F2 shown better particle size and % entrapment efficiency and also the drug release was 99.72% within 24h in slow and controlled manner when compared with control. The particle size and Zeta potential of the optimized atorvastatin proniosomal gel was found to be 65.72 and -10.5 respectively. Optimized batch of Proniosomes was used for the preparation of Atorvastatin - based proniosomal hydrogel by incorporating hydrated Proniosomes to Carbopol matrix to enhance the stability and viscosity of the system. The enhanced skin permeation for prolonged period of time, may lead to improved efficacy and better patient compliance. From in vivo studies the maximal concentrations (Cmax) of drug was significantly reduced while the areas under the plasma concentration–time curve (AUC) and t1/2 were evidently increased and extended. This study suggests that proniosomal gel of atorvastatin would be a promising alternative to improve the bioavailability problems of atorvastatin.