Bioavailability enhancement of voriconazole using liposomal pastilles: Formulation and experimental design investigation

Abstract

Oral mucosa offers several advantages in the delivery of therapeutic molecules. It avoids presystemic metabolism, Nanoencapsulation techniques might be applied to conquer physical, chemical challenges and enhance drug penetration, formulation performance, prolonging drug residence time, and improving sensorial feeling. The present investigation is aimed to formulate liposomal pastilles with high bioavailability. Voriconazole Liposomes (VL) were produced by utilizing varied ratios of soya lecithin (SL) and cholesterol (CH) by solvent Injection method. RSM is utilized to identify the optimized formulation, as this design provides a thorough understanding of a process and also has great utilization in originating the robustness of the product. The main impact and interaction terms of the formulation variables were assessed quantitatively utilizing a mathematical-statistical approach indicating that both independent variables have significant (‘P’ value < 0.05) effects on particle size (‘P’ value: 0.0142), percentage entrapment efficiency (‘P’ value: 0.0120), percentage drug release through the dialysis membrane (‘P’ value: 0.0105), percentage drug release through porcine buccal mucosa (‘P’ value: 0.0171) and percentage zone of inhibition (‘P’ value: 0.0305). Optimal liposomal encapsulated in noticed in 15:10 lecithin: cholesterol concentration (VLP-6). Higher Lecithin and Cholesterol quantity in the liposome formulations resulted in lower drug entrapment efficiency and drug release when compared with middle levels of lecithin and cholesterol content formulation. The pastilles were prepared from the optimized liposomal formulation with a modified method reported in British Pharmaceutical Codex, 1907. These liposomal pastilles were subjected to evaluation of physicochemical parameters, In vitro drug release studies, stability studies, and In vivo bioavailability studies in comparison with pure voriconazole pastilles (PVP). The statistical data analysis results indicated that there was a significant difference in T_max, K_a, t_{1/2 abs}, t_{1/2 elim,} AUC_0–24, AUC_0-∞, AUMC_0–24 and AUMC_0-∞, values among PVP and VLP-6. There was no significant difference in C_max, K_el, MRT_0–24 and MRT_0-∞values among pure voriconazole pastilles and optimized liposomal formulation.

Keywords:

• Liposomes
• voriconazole
• antifungal
• response surface methodology
• lecithin
• cholesterol

Acknowledgments

The authors are thankful to University Grants Commission (UGC, New Delhi, India) for providing financial assistance for carrying the research work. The authors are also thankful to M/s. GITAM Institute of Pharmacy, GITAM University, Visakhapatnam, Andhra Pradesh, India for providing facilities and giving support to conduct this work.

Ethics approval and consent to participate

The protocol for the study was approved by the Institute of Animals Ethics Committee (IAEC; Reg. No: 1287/PO/ac/2009/CPCSEA).

Disclosure statement

The authors declare no conflicts of interest.

Author contributions

VDV: literature review, supervision, and corrections. VSVT: formulation development. SL: plan of Investigation. All the authors have read and approved the manuscript.

Data availability statement

The data generated or analyzed during this study are included in this article, if any excess data required will be available from the corresponding author on reasonable request.

Additional information

Funding

This research received financial assistance from University Grants Commission (UGC, New Delhi, India) for carrying the research work.