Advancements in Antiviral Therapy: Favipiravir Sodium in Nasal Formulation

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY AAPS PharmSciTech Pub Date : 2024-11-26 DOI:10.1208/s12249-024-02986-5

Priti Darne, Shankar Vidhate, Somesh Shintre, Somnath Wagdare, Dhiraj Bhamare, Nisha Mehta, Vishal Rajagopalan, Sriram Padmanabhan

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Abstract

Favipiravir (FPV) is an Active Pharmaceutical Ingredient (API) known to have lower solubility in aqueous solvents. In the current study, efforts were made to generate a crystalline Favipiravir Sodium Salt (NaFPV) for enhanced solubility in aqueous media. The in-house generated NaFPV was characterized by NMR studies and its sodium content was determined by Flame Emission Spectroscopy (FES) as a confirmation of salt formation. Its solubility was determined where-in the solubility of NaFPV in water was about 100 times greater than FVP. FPV and NaFPV nasal spray formulations were prepared and its activity was determined against human coronavirus (hCoV) 229E strain. In the anti-hCoV assay as compared to FPV, NaFPV showed almost threefold higher anti-viral activity than its unmodified counterpart. Accelerated stability and spray pattern characteristics of both the formulations were studied. Interestingly, NaFPV showed higher physical stability during storage at conditions 40 ± 2 °C/ 75% ± 5% RH. The nasal spray formulations of both FPV and NaFPV showed ideal plume geometry and spray pattern of acceptable specifications. Due to its improvement in terms of solubility, NaFPV will have higher rate and extent of absorption, and faster onset of the therapeutic effect and may appear to be a feasible alternative to regular favipiravir for use in solid dosage forms.

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抗病毒疗法的进展：鼻用制剂法维拉韦钠

已知法维拉韦（Favipiravir，FPV）是一种活性药物成分（API），在水性溶剂中的溶解度较低。在本研究中，我们努力生成结晶的法维拉韦钠盐（NaFPV），以提高其在水介质中的溶解度。通过核磁共振研究对内部生成的 NaFPV 进行了表征，并通过火焰发射光谱（FES）测定其钠含量，以确认盐的形成。NaFPV 在水中的溶解度约为 FVP 的 100 倍。制备了 FPV 和 NaFPV 鼻腔喷雾制剂，并测定了它们对人类冠状病毒（hCoV）229E 株的活性。在抗 hCoV 试验中，与 FPV 相比，NaFPV 的抗病毒活性几乎是其未改性制剂的三倍。对两种制剂的加速稳定性和喷雾模式特性进行了研究。有趣的是，NaFPV 在 40±2 °C/75%±5% 相对湿度条件下储存时显示出更高的物理稳定性。FPV 和 NaFPV 的鼻腔喷雾配方都显示出理想的羽流几何形状和喷雾模式，达到了可接受的规格。由于 NaFPV 在溶解度方面的改进，它的吸收率和吸收范围会更高，治疗效果也会更快显现，因此可以作为常规法非拉韦的可行替代品，用于固体制剂中。

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来源期刊

AAPS PharmSciTech 医学-药学

CiteScore

6.80

自引率

3.00%

发文量

264

审稿时长

2.4 months

期刊介绍： AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.