Enhancement of oral bioavailability of anti-HIV drug rilpivirine HCl through nanosponge formulation^*

Abstract

Objective: To synthesize β cyclodextrin nanosponges using a novel and efficient microwave mediated method for enhancing bioavailability of Rilpivirine HCl (RLP).

Significance: Belonging to BCS class II RLP has pH dependent solubility and poor oral bioavailability. However, a fatty meal enhances its absorption hence the therapy indicates that the dosage form be consumed with a meal. But then it becomes tedious and inconvenient to continue the therapy for years with having to face the associated gastric side effects such as nausea.

Method: Microwave synthesizer was used to mediate the poly-condensation reaction between β-cyclodextrin and cross-linker diphenylcarbonate. Critical parameters selected were polymer to cross-linker ratio, Watt power, reaction time and solvent volume. Characterization studies were performed using FTIR, DSC, SEM, ¹H-NMR and PXRD. Molecular modeling was applied to confirm the possibility of drug entrapment. In vitro drug dissolution followed by oral bioavailability studies was performed in Sprawley rats. Samples were analyzed using HPLC.

Results: Microwave synthesis yields para-crystalline, porous nanosponges (∼205 nm). Drug entrapment led to enhancement of solubility and a two-fold increase in drug dissolution (P < 0.001) following Higuchi release model. Enhanced oral bioavailability was observed in fasted Sprawley rats where C_max and AUC_0-∞ increases significantly (C_max of NS∼ 586 ± 5.91 ng/mL; plain RLP ∼310 ± 5. 74 ng/mL).

Conclusion: The approach offers a comfortable dosing zone for AIDs patients, negating the requirement of consuming the formulation in a fed state due to enhancement in drugs’ oral bioavailability.

Keywords:

• Rilpivirine hydrochloride (RLP)
• microwave synthesis
• nanosponge
• oral bioavailability
• anti-HIV drug

Acknowledgement

The authors are thankful to Ms. Fatma Rafiq Zakaria, Chairman of Maulana Azad Educational Trust, for her endless encouragement and support.

Disclosure statement

Authors declare no conflict of interest. All authors have contributed in the research.

Additional information

Funding

Dr. Ms. Rana Zainuddin is thankful to the University Grants Commission, India for funding this research work (Minor research grant 47–856/13 WRO).