Alsaab Hashem, Alzhrani Rami M, Boddu Sai H S
a Department of Pharmacy Practice , College of Pharmacy and Pharmaceutical Sciences, The University of Toledo , Toledo, OH , USA.
Drug Dev Ind Pharm. 2016 Aug;42(8):1258-66. doi: 10.3109/03639045.2015.1122610. Epub 2015 Dec 21.
The overall objective of this work is to determine the percutaneous absorption of chlorpromazine hydrochloride from pluronic lecithin organogels (PLO gels) and verify the suitability of topically applied chlorpromazine hydrochloride PLO gels for use in hospice patients for relieving symptoms such as vomiting and nausea during the end stages of life.
PLO gels of chlorpromazine hydrochloride were prepared using isopropyl palmitate (IPP) or ricinoleic acid (RA) as oil phase. In vitro percutaneous absorption of chlorpromazine hydrochloride was assessed through porcine ear and human abdominal skin. Further, the theoretical steady state plasma concentration (Css) of chlorpromazine was calculated from the flux values.
The pH, viscosity, and stability of both PLO gels prepared with IPP and RA were comparable. The thixotropic property of RA PLO gel was found to be better than that of IPP PLO gel. The permeation of chlorpromazine hydrochloride was higher from RA PLO gel than from IPP PLO gel and pure drug solution. Theoretical Css of chlorpromazine from pure drug solution, IPP PLO gel and RA PLO gel were found to be 1.05, 1.20, and 1.50 ng/ml, respectively. PLO gels only marginally increased the flux and theoretical Css of chlorpromazine.
From this study, it is clearly evident that PLO gels fail to achieve required systemic levels of chlorpromazine following topical application. Chlorpromazine PLO gel may not be effective in treating nausea and vomiting for hospice patients with swallowing difficulties.
本研究的总体目标是测定盐酸氯丙嗪从普朗尼克卵磷脂有机凝胶(PLO凝胶)中的经皮吸收情况,并验证局部应用的盐酸氯丙嗪PLO凝胶用于临终关怀患者缓解生命末期呕吐和恶心等症状的适用性。
以棕榈酸异丙酯(IPP)或蓖麻油酸(RA)为油相制备盐酸氯丙嗪PLO凝胶。通过猪耳皮肤和人腹部皮肤评估盐酸氯丙嗪的体外经皮吸收情况。此外,根据通量值计算氯丙嗪的理论稳态血药浓度(Css)。
用IPP和RA制备的两种PLO凝胶的pH值、粘度和稳定性相当。发现RA PLO凝胶的触变性优于IPP PLO凝胶。盐酸氯丙嗪从RA PLO凝胶中的渗透高于从IPP PLO凝胶和纯药物溶液中的渗透。纯药物溶液、IPP PLO凝胶和RA PLO凝胶中氯丙嗪的理论Css分别为1.05、1.20和1.50 ng/ml。PLO凝胶仅略微增加了氯丙嗪的通量和理论Css。
从本研究中可以明显看出,局部应用PLO凝胶未能达到所需的氯丙嗪全身水平。盐酸氯丙嗪PLO凝胶可能对吞咽困难的临终关怀患者治疗恶心和呕吐无效。