Formulation development, characterization, and evaluation of bedaquiline fumarate – Soluplus^® – solid dispersion

Abstract

Bedaquiline fumarate (BQF) is classified as a BCS class II drug and has poor water solubility and dissolution rate, which ultimately compromises bioavailability. The objective of this study is to improve the biopharmaceutical properties of BQF through a solid dispersion system by using Soluplus^®. Two solid dispersion systems were prepared i.e. binary solid dispersion (BSD) and ternary solid dispersion (TSD) where 14.31-fold and 20.43-fold increase in solubility of BQF was observed with BSD and TSD in comparison to BQF. In our previous research work, we explored the BSD and TSD of BQF with a crystalline polymer, poloxamer 188, which showed an increment in the solubility of BQF. In the current research, amorphous Soluplus^® polymer was selected to formulate BSD and TSD with BQF and showed higher solubility than poloxamer 188. The various solid and liquid state characterization results confirmed the presence of an amorphous form of BQF inside solid dispersion. The Fourier transform infrared spectroscopy showed no chemical interactions between BQF and polymer. The cellular uptake results demonstrated higher uptake in Caco-2 cell lines. Pharmacokinetic studies showed enhanced solubility and bioavailability of TSDs. Hence, the present research shows a promising formulation strategy for enhancing the biopharmaceutical performance of BQF by increasing its solubility.

Graphical Abstract

Keywords:

• Multidrug-resistant tuberculosis
• dissolution rate
• tocopherol polyethylene glycol succinate
• differential scanning calorimetry

Acknowledgment

We acknowledge the Department of Pharmaceuticals (DoP), Ministry of Chemicals and Fertilizers, Government of India, for providing necessary facilities to execute this research work. The NIPER-Raebareli communication number for this manuscript is NIPER-R/Communication/537.

Declaration

The in vivo pharmacokinetic study with animals were performed according to protocol duly approved by Institutional Animal Ethics Committee (IAEC) with approval number NIPER/RBL/IAEC/31/Aug 2019 in accordance with the guidelines of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA).

Disclosure statement

The authors clarify that the formulation part of this research work has been filed for Indian patent at Indian Patent Office (IPO), Mumbai, India; Application No.: 202011040038; Date of Application: 16/09/2020.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.