Khan Rahman Ullah, Shah Shefaat Ullah, Rashid Sheikh Abdur, Naseem Faiza, Shah Kifayat Ullah, Farid Arshad, Hakeem Khalid Rehman, Kamli Majid Rasool, Althubaiti Eman Hillal, Alamoudi Soha A
Skin/Regenerative Medicine and Drug Delivery Research, GCPS, Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Pakistan.
Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, Pakistan.
Polymers (Basel). 2022 May 9;14(9):1922. doi: 10.3390/polym14091922.
Nanoemulsions are promising drug delivery systems for the administration of poorly soluble drugs like lornoxicam (LRX) by oral or parenteral routes. Such formulations work perfectly for transdermal delivery of lornoxicam-type drugs. It has also been established that formulating such a delivery system is highly dependent on the presence, type, and concentration of excipients taking part in the formulation. The inherent characteristics of nanoemulsion (NE), i.e., smaller globule size and excipient nature, facilitate the drug's passage through skin. The current study was aimed at the development of an NE-based formulation of LRX to improve the drug solubility in vitro as well as to enhance drug skin permeation to promote therapeutic outcome in appropriate time. Spontaneous self-emulsification technique was utilized to develop optimized LRX-encapsulated NE-based formulations. ATR-FTIR spectra of the pure drug and various formulations did not show any interaction between the drug and various formulation excipients showing compatibility. Globule size for stable formulations ranged between 63-168 nm. These formulations were characterized for viscosity, surface tension, pH, drug encapsulation efficiency, in vitro drug release, and drug skin permeation studies. Chitosan-decorated optimized NE formulation of LRX showed about 58.82% cumulative drug release, showing an anomalous non-Fickian diffusion mechanism of drug release. Drug encapsulation efficiency, in vitro drug release, and skin permeation studies exhibited promising results. An appreciable drug entrapment efficiency was exhibited by optimized NE formulations LRX-6, 71.91 ± 3.17% and C-LRX, 65.25 ± 4.89%. Permeability parameters like enhancement ratio (Er), permeability constant (Kp), and steady state flux (Jss) showed higher values and exhibited good results based on formulation type. The selected promising formulation type "LRX-6" showed significantly different results as compared to other formulations (LRX-4, 5, and 7). The skin permeation property of the LRX-6 formulation was compared to similar chitosan-based formulations and was found to have better skin permeation results than chitosan-based formulations. This study clearly exhibited that an LRX-containing NE-based formulation can be formulated to form a stable drug delivery system. Such formulations are promising in terms of physicochemical characteristics, improved solubility, and high skin permeation potential.
纳米乳剂是一种很有前景的药物递送系统，可通过口服或肠胃外途径给药难溶性药物，如氯诺昔康（LRX）。这类制剂非常适合氯诺昔康类药物的透皮给药。还已证实，制备这种递送系统高度依赖于参与制剂的辅料的存在、类型和浓度。纳米乳剂（NE）的固有特性，即较小的球粒尺寸和辅料性质，有利于药物透过皮肤。本研究旨在开发一种基于纳米乳剂的LRX制剂，以提高药物的体外溶解度，并增强药物的皮肤渗透，从而在适当时间促进治疗效果。采用自发自乳化技术开发了优化的包封LRX的纳米乳剂制剂。纯药物和各种制剂的衰减全反射傅里叶变换红外光谱（ATR-FTIR）未显示药物与各种制剂辅料之间有任何相互作用，表明具有相容性。稳定制剂的球粒尺寸在63-168nm之间。对这些制剂进行了粘度、表面张力、pH值、药物包封率、体外药物释放和药物皮肤渗透研究。壳聚糖修饰的优化LRX纳米乳剂制剂显示约58.82%的累积药物释放，表明药物释放具有非菲克反常扩散机制。药物包封率、体外药物释放和皮肤渗透研究均显示出有前景的结果。优化的纳米乳剂制剂LRX-6的药物截留率为71.91±3.17%，C-LRX为65.25±4.89%，表现出可观的药物截留效率。增强比（Er）、渗透常数（Kp）和稳态通量（Jss）等渗透参数显示出较高的值，并根据制剂类型表现出良好的结果。所选的有前景的制剂类型“LRX-6”与其他制剂（LRX-4、5和7）相比显示出显著不同的结果。将LRX-6制剂的皮肤渗透性能与类似的壳聚糖基制剂进行比较，发现其皮肤渗透结果优于壳聚糖基制剂。本研究清楚地表明，可以制备含LRX的纳米乳剂制剂以形成稳定的药物递送系统。这类制剂在物理化学特性、改善溶解度和高皮肤渗透潜力方面很有前景。
