Comprehensive evaluation of xylometazoline hydrochloride formulations: Ex-vivo and in-vitro studies

IF 4.4 2区 医学 Q1 PHARMACOLOGY & PHARMACY
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Abstract

Xylometazoline is a well-established nasal decongestant that has been used alone and in combination with dexpanthenol as an over the counter (OTC) medicine. Considering the possibility of further improvement of xylometazoline nasal formulations, hyaluronic acid (HA) was evaluated as an additional ingredient. The aim of this study was to investigate the permeation, mucosal retention, and mucoadhesion properties of a new xylometazoline-HA [Xylo-HA] formulation ex vivo and to explore the potential benefits of incorporating HA in the formulation in vitro. Sheep nasal mucosa was used in the ex vivo study, where Xylo-HA was compared with xylometazoline alone [Xylo-Mono], and in combination with dexpanthenol [Xylo-Dex] to understand the impact of formulation changes. The permeation of xylometazoline was generally low (Xylo-Mono 11.14 ± 4.75 %, Xylo-HA 14.57 ± 5.72 % and Xylo-Dex 11.00 ± 3.05 % of the applied dose). The steady state fluxes of xylometazoline were determined as 12.64 ± 3.52 μg/cm2h, 14.94 ± 3.38 μg/cm2h and 12.19 ± 2.05 μg/cm2h for Xylo-Mono, Xylo-HA and Xylo-Dex, respectively. No significant differences were observed between the formulations in the permeation nor mucosal retention studies (p > 0.05 for all), while Xylo-HA exhibited superior mucoadhesive proprieties (p < 0.05 for all). The effects on wound healing and barrier integrity of the three xylometazoline formulations were tested in vitro on HaCaT cells. To better elucidate the role of HA, an additional HA formulation without xylometazoline was prepared (HA-Mono). A scratch test was performed to evaluate wound healing, revealing that the test formulations did not achieve complete wound closure within 72 h and demonstrated a similar effect at the end of the testing period. To assess the effect on barrier integrity, cells were treated for 5 days with daily measurements of transepithelial electrical resistance (TEER). At the end of the experiment, Xylo-Dex showed a moderate 14 % increase in TEER, while Xylo-Mono did not significantly affect this parameter. TEER rose by 951 % in the Xylo-HA, and by 10497 % in the HA group, suggesting that incorporating HA led to enhanced barrier function. Further clinical studies are recommended to better understand the clinical implications and efficacy of the Xylo-HA formulation, with particular focus on the role of HA.

Abstract Image

盐酸甲氧甲唑啉制剂的综合评估:体内外研究
甲氧甲唑啉是一种久负盛名的鼻腔减充血剂,曾作为非处方药(OTC)单独或与右泛醇联合使用。考虑到进一步改进甲氧甲唑啉鼻腔制剂的可能性,研究人员对透明质酸(HA)作为附加成分进行了评估。本研究的目的是调查一种新型甲氧甲唑啉-HA [Xylo-HA]制剂在体内的渗透、粘膜保留和粘附特性,并在体外探索在制剂中加入透明质酸的潜在益处。体内外研究使用的是绵羊鼻粘膜,将 Xylo-HA 与单独使用的异丙甲唑啉 [Xylo-Mono] 和与右泛醇 [Xylo-Dex] 混合使用的异丙甲唑啉进行比较,以了解配方变化的影响。甲氧甲唑啉的渗透率普遍较低(Xylo-Mono 为 11.14 ± 4.75 %,Xylo-HA 为 14.57 ± 5.72 %,Xylo-Dex 为 11.00 ± 3.05 %)。经测定,Xylo-Mono、Xylo-HA 和 Xylo-Dex 的甲基唑啉稳态通量分别为 12.64 ± 3.52 μg/cm2h 、14.94 ± 3.38 μg/cm2h 和 12.19 ± 2.05 μg/cm2h。在渗透性和粘膜保留研究中,未观察到配方之间存在明显差异(均为 p > 0.05),而 Xylo-HA 则表现出更优越的粘附性(p > 0.05)。
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来源期刊
CiteScore
8.80
自引率
4.10%
发文量
211
审稿时长
36 days
期刊介绍: The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics. Topics covered include for example: Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids) Aspects of manufacturing process design Biomedical aspects of drug product design Strategies and formulations for controlled drug transport across biological barriers Physicochemical aspects of drug product development Novel excipients for drug product design Drug delivery and controlled release systems for systemic and local applications Nanomaterials for therapeutic and diagnostic purposes Advanced therapy medicinal products Medical devices supporting a distinct pharmacological effect.
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