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

• Published in: Pharmaceutical development and technology Vol. 29; no. 5; pp. 492 - 503
• Main Authors: Pardhi, Vishwas P, Patel, Manisha, Jain, Keerti
• Format: Journal Article
• Language: English
• Published: England 01-06-2024
• Subjects: Animals; Antitubercular Agents - administration & dosage; Antitubercular Agents - chemistry; Antitubercular Agents - pharmacokinetics; Antitubercular Agents - pharmacology; Biological Availability; Caco-2 Cells; Chemistry, Pharmaceutical - methods; Diarylquinolines - chemistry; Diarylquinolines - pharmacokinetics; Diarylquinolines - pharmacology; Drug Compounding - methods; Humans; Male; Poloxamer - chemistry; Polyethylene Glycols - chemistry; Polyvinyls - chemistry; Rats; Solubility; dissolution rate; Multidrug-resistant tuberculosis; tocopherol polyethylene glycol succinate; differential scanning calorimetry
• ISSN: 1083-7450; 1097-9867; 1097-9867
• DOI: 10.1080/10837450.2024.2348585

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.