Co-amorphous Approach for Enhancing Rilpivirine Oral Bioavailability using CYP3A4 Inhibitor as a Co-former

Rilpivirine, a BCS class II drug, has low water solubility (0.0166 mg/ml) and oral bioavailability of (32%), limiting its HIV treatment delivery. This research aimed to improve rilpivirine's solubility and bioavailability by developing a co-amorphous system (CAMS) using nicotinamide as co-former. Nicotinamide selection was based on knowledge-based methods such as Hansen solubility parameter, Flory–Huggins interaction parameter, and molecular modeling. CAMS was prepared using solvent evaporation and quench cooling at molar ratio of 1:1, 1:2, and 2:1. Phase solubility study showed 1:1 molar ratio was most suitable for complex formation. Fourier transform infrared spectroscopy, powder X-ray diffraction, differential scanning calorimetry, and field-emission scanning electron microscopy confirmed CAMS formation. Saturation solubility studies showed rilpivirine's solubility increased 38-fold in CAMS compared to pure drug. In vitro drug release and ex vivo permeation study demonstrated 2.86- and 2.87-fold enhancement in drug release and permeation. Pharmacokinetic study in Wistar rats showed 2.49-fold improvement in oral bioavailability, attributed to improved dissolution and CYP3A4 enzyme inhibition by nicotinamide. Stability studies confirmed CAMS maintained its amorphous state for over three months, as shown by DSC, PXRD, FE-SEM, solubility and dissolution studies. The CAMS of rilpivirine and nicotinamide, prepared through solvent evaporation at 1:1 molar ratio, enhanced rilpivirine's solubility, dissolution, permeation, and oral bioavailability, offering a promising antiretroviral drug delivery strategy.

• Publication year

  2025

• Venue

  AAPS PharmSciTech

• Publication date

  2025-11-05

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1208/s12249-025-03222-4PMID 41188591
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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