Shah Jigar, Nair Anroop B, Shah Hiral, Jacob Shery, Shehata Tamer M, Morsy Mohamed Aly
Institute of Pharmacy, Nirma University, Ahmedabad 382481, India.
College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
Asian J Pharm Sci. 2020 Nov;15(6):786-796. doi: 10.1016/j.ajps.2019.05.001. Epub 2019 Jun 19.
Oral therapy of tramadol, an opiate analgesic, undergoes extensive hepatic metabolism and requires frequent administration. Transdermal therapy by virtue can overcome these issues and can improve the efficacy and reduce abuse liability of tramadol. The aim of this research was to investigate the possibility of transdermal delivery of tramadol by formulating proniosome gel and evaluate its therapeutic potential . The effect of formulation composition as well as amount of drug on physicochemical characteristics of prepared proniosomes were examined. Best proniosome gel (F4) was selected and evaluated for drug release, stability and transdermal efficacy by and experiments. The vesicles demonstrated optimal properties including spherical shape, nanosize with good entrapment efficiency, adequate zeta potential, higher stability and greater transdermal flux. The amorphization and dispersion of tramadol in the aqueous core of proniosome vesicles was confirmed by differential scanning calorimeter. Release profile of F4 was distinct ( < 0.001) from control and displayed steady and prolonged tramadol release by Fickian diffusion. Transdermal therapy of F4 showed prominent reduction of induced twitches ( < 0.005) in mice and edema ( < .05) in rats, as compared to oral tramadol. The improvement in clinical efficacy of tramadol in transdermal therapy is correlated with the pharmacokinetic data observed. In conclusion, the observed improvement in antinociceptive and anti-inflammatory effects from proniosome carriers signifies its potential to be a suitable alternative to oral therapy of tramadol with greater efficacy.
阿片类镇痛药曲马多的口服疗法会经历广泛的肝脏代谢，需要频繁给药。经皮疗法则可以克服这些问题，并能提高曲马多的疗效和降低其被滥用的可能性。本研究的目的是通过制备前体脂质体凝胶来研究曲马多经皮给药的可能性，并评估其治疗潜力。研究了制剂组成以及药物用量对所制备前体脂质体物理化学特性的影响。通过相关实验选择并评估了最佳前体脂质体凝胶（F4）的药物释放、稳定性和经皮疗效。这些囊泡表现出最佳特性，包括球形、纳米尺寸、良好的包封率、合适的zeta电位、更高的稳定性和更大的经皮通量。差示扫描量热法证实了曲马多在前体脂质体囊泡水核中的非晶化和分散。F4的释放曲线与对照有显著差异（P<0.001），并通过菲克扩散显示出稳定且持续的曲马多释放。与口服曲马多相比，F4的经皮疗法在小鼠中显示出诱导抽搐显著减少（P<0.005），在大鼠中显示出水肿减轻（P<0.05）。曲马多经皮疗法临床疗效的改善与所观察到的药代动力学数据相关。总之，前体脂质体载体在镇痛和抗炎作用方面观察到的改善表明其有潜力成为曲马多口服疗法更有效的合适替代方案。
