Formulation and In-vitro Characterization of Nefopam Hydrochloride as In-situ nasal gel

Abstract

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Abstract Nefopam HCl (NF) is a non-narcotic, non-opioid, centrally acting analgesic. It has a limited bioavailability (approximately 36%) as a result of liver first-pass hepatic metabolism.

This study aims to develop and improve mucoadhesive nasal thermosensitive in-situ gel of nefopam hydrochloride to prolong nasal residence time for pain management.

In situ gel of NF formulas (No. 1-48, 20 mg/ml NF) were formulated by the cold approach using different concentrations of thermosensitive Poloxamer 407 alone or with a combination of Poloxamer 188 with a mucoadhesive polymer(s); Hydroxypropyl methylcellulose K4M, Carbopol® 934, Methylcellulose and Hyaluronic acid polymers.

The prepared formulas were subjected to gelation temperature and time, clarity and appearance, and these were the criteria for the initial selection of formulas. The pH, gel strength, drug content, gel spreadability, osmolarity, mucoadhesive force determination, viscosity, and in-vitro drug release of formulations was performed, the most suitable formulas were subjected to permeation study, Fourier transform infrared (FTIR) compatibility studies, and stability study.

The results showed that formulas No. (F 13,16,17,20,21,24,41,44,45) passed the initial gelation temperature and gelling capacity and appearance criteria as well as other characterization tests, but only they differentiate in drug release in comparison with a NF aqueous solution as a control. The formulas No. F21 and 45 (Poloxamer 407 17% and Hyaluronic acid 0.25%, Poloxamer 407 17% and Methylcellulose 0.1%, respectively) show similarity in release pattern in comparison with control.

The formula No. F21 show enhanced ex-vivo permeation through sheep nasal mucosa in comparing with control, that attributed to the permeation enhancing effects as well as due to increasing residence time of mucoadhesive polymers.

No interaction between NF and other additives in both formulas, according to FTIR studies.

In conclusion, a promising non-invasive thermosensitive nasal mucoadhesive in situ gel of nefopam hydrochloride can be prepared successfully by using poloxamer 407 based in situ gel together with mucoadhesive polymers.