Enhancement of solubility of paclitaxel by applying factorial design

Abstract

Background: The poor aqueous solubility and low bioavailability of antineoplastic drugs restrict the oral route for the cancer therapy. However, specific nanotechnologies developed to address this issue. The self-micro emulsifying drug delivery system (SMEDDS) is an imperative tool in solving a lipophilic drug's low solubility and bioavailability issue. Paclitaxel (PTX) is an antineoplastic drug used to treat various kinds of cancer, especially ovarian and breast cancers. It has low aqueous solubility (0.3 μg/ml in water), resulting in poor bioavailability. This study focuses upon formulating SMEDDS incorporating PTX to increase the drug's aqueous solubility. Castor oil (Surfactant), Tween 80 (surfactant), and Transcutol (co-surfactant) were used to formulate SMEDDS. Two independent factors, concentrations of oil and surfactant, were chosen. Two dependent factors, emulsification time and in vitro drug release, were chosen. 32 factorial design analyses give a mathematical expression, which helps to study the effect of an independent factor on a dependent factor. All the nine formulations B1-B9 evaluated for globule size, zeta potential, and present drug content. Results: The globule size found is 127–217 nm range, which indicates the formation of the transparent microemulsion; zeta potential fields between −4.29 ± 1.1 and −33.05 ± 4.5 indicate suitable stable formulation. Nearly 63%–84% drug content suggests that the drug, incorporated into prepared SMEDDS. Statistical analysis shows that an increasing amount of surfactant decreases emulsification time; this may also reduce the average droplet size of the resultant microemulsion. With the increase in the concentration of tween 80, PTX release also increased. Rapid and more extent of PTX released from formulated SMEDDS indicate that the aqueous solubility of PTX has increased. B9 formulation is the optimized formulation based on higher per cent cumulative drug release 98% at the end of 60 min, 58% of pure PTX powder solubilized in the dissolution medium. Conclusion: In vitro drug release study proved that the prepared SMEDDS has acceptable properties of immediate release dosage forms. The enhanced solubility of PTX will increase its bioavailability.

Keywords

• antineoplastic
• bioavailability
• experimental design
• lipophilicity
• paclitaxel
• self-emulsification