Bedaquiline loaded Soluplus® Micelles for Improving Solubility and Intestinal Permeability: Formulation, Optimization, and Ex vivo Evaluation

Abstract

Oral delivery of bedaquiline is the preferred route of drug delivery in the treatment of multidrug-resistant tuberculosis, although its poor bioavailability leads to poor patient compliance. To overcome this problem, we have prepared bedaquiline loaded Soluplus® micelles to improve the solubility and intestinal permeability of bedaquiline. The micelles were successfully prepared by the thin film hydration method with entrapment efficiency of 98.65±0.68% and size of 73.30±12.28 nm.

Highlights

• Bedaquiline loaded Soluplus® micelles with particle size 73.30±12.28 nm was formulated.
• Micelle preparation improved the aqueous solubility of bedaquiline by 25 folds.
• Micellar system was found to be stable in SGF and SIF for 2 hr and 6 hr, respectively.
• Bedaquiline loaded micelles showed dose dependent increment in cell uptake.
• The amphiphilic nature of Soluplus® enhanced the cell permeation through intestinal wall.

The micelles were evaluated for morphology, stability, flow properties, drug release, solubility, and permeability. The flow property analysis of lyophilized micelles indicated that Bedaquiline containing micelles (20 mg equivalent) could be easily incorporated into ’00’ number capsules. The solubility study showed 25 times increment in the solubility of bedaquiline, whereas permeability study showed 3.5 times higher permeability for bedaquiline loaded micelles than free bedaquiline.

The in vitro cell line studies with Caco-2 cells showed desired cell viability and dose dependent increment in cell uptake. In conclusion, Soluplus® micelles showed the ability to protect the bedaquiline in harsh physiologic environments with significant enhancement in solubility and permeability.

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Materials

Bedaquiline was purchased from Clearsynth India Private Limited (Hyderabad, India). Soluplus® was generously gifted by BASF India Limited (Mumbai, India). Span 20 and methanol (analytical grade and HPLC grade) were purchased from Sigma-Aldrich (St. Louis, Germany) and Merck Life Sciences Pvt Ltd (Bengaluru, India), respectively. The triple distilled water (TDW) was generated using an in-house Millipore water purification assembly (Millipore Corp., USA).

Krishnapal, Parth Patel, Vishwas Pardhi, Keerti Jain, Bedaquiline loaded Soluplus® Micelles for Improving Solubility and Intestinal Permeability: Formulation, Optimization, and Ex vivo Evaluation, Journal of Drug Delivery Science and Technology, 2025, 106656, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2025.106656.

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