Preparation and optimization of nilotinib self-micro-emulsifying drug delivery systems to enhance oral bioavailability

Abstract

Objective: The objective of the current research was to prepare self-micro-emulsifying drug delivery systems (SMEDDS) for BCS class II drug, nilotinib to enhance its oral bioavailability.

Methodology: Different types of excipients like oil, surfactant, and co-surfactant were evaluated for drug solubility. Among the screened excipients, Capryol 90, Transcutol HP, and Tween 80 were selected as oil, co-surfactant, and surfactant, respectively, to construct a ternary phase diagram to identify a homogenous mixture. Characterization performed for the prepared SMEDDS for its particle size/droplet size, emulsification time, phase separation, droplet morphology, in vitro drug release, and oral bioavailability.

Results: Prepared SMEDDS showed the highest of 87% drug release in in vitro drug release experiment. SMEDDS drug release was superior over suspension formulation, which could be attributed to oil/surfactant ratios and particle size of the SMEDDS. The acquired pharmacokinetic parameters indicate that twofold increase in systemic exposure of SMEDDS compared with nilotinib suspension formulation. A similar twofold increase in relative oral bioavailability was also observed when compared SMEDDS formulation with suspension formulation. Delayed T_max (time to reach peak plasma concentrations) was observed with SMEDDS over suspension formulation, which was evident by slow rate of absorption of nilotinib from SMEDDS.

Conclusion: This research demonstrated that SMEDDS could be an effective approach to improve solubility and oral bioavailability for the BCS class II poorly soluble nilotinib.

Keywords:

• Nilotinib
• BCS class II
• SMEDDS
• characterization
• oral bioavailability
• rats

Disclosure statement

No potential conflict of interest was reported by the author(s).