Box-Behnken design

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.

Acyclovir has low bioavailability mainly due to low solubility. In this study, solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of acyclovir were developed with the objective of improving its solubility. Initial screening was carried out to select the excipients. Ternary phase diagrams were constructed to detect the nanoemulsification region. The nanoemulsion systems selected from the phase diagram were characterized for their robustness to dilution and cloud point temperature. Box- Behnken design was then applied for further optimization. The formulations obtained were further characterized for their droplet size and entrapment efficiency. The best formulation was converted to S-SNEDDS by simple adsorption technique. The liquid SNEDDS (L-SNEDDS) was adsorbed onto microcrystalline cellulose in 1:1 ratio. Zeta potential, differential scanning calorimetry, scanning electron microscopy was then carried out. In vitro drug release was studied by comparing the S-SNEDDS with pure drug. The L-SNEDDS formulation which was converted to S-SNEDDS showed particle size of 147 nm. The formulation was found to be robust to dilution and showed cloud point at 86 ◦C. Negative zeta potential meant, there was no coalescence of globules. SEM studies of nanoemulsion demonstrated that the globules in L-SNEDDS were indeed adsorbed on the MCC. Results of DSC confirmed that the drug was incorporated in the S-SNEDDS that was formulated. The in vitro drug release from acyclovir S-SNEDDS was found to be considerably higher in comparison to that of the pure drug. Therefore, it can be concluded that acyclovir loaded S-SNEDDS improved the solubility and release characteristics of the drug.