Patwardhan Sunetra, Patil Manohar, Sockalingam Anbazhagan
Sinhgad College of Pharmacy, 44/1, Vadgaon (Bk), Off Sinhgad Road, Pune- 411041, Maharashtra, India.
Department Pharmacognosy, Marathwada Mitramandal College of Pharmacy, Pimpri, Pune, India.
Recent Pat Drug Deliv Formul. 2017;11(1):28-35. doi: 10.2174/1872211311666170105114459.
The absorption of drug through skin avoids many side effects of oral route like gastric irritation, nausea, systemic toxicity etc and thus improves patient compliance. Naproxen sodium (NPRS) is one of the potent NSAID agents.
The present study was aimed to develop and evaluate the gel formulation containing NPRS for transdermal drug delivery reducing the side effects and improving patient compliance. The patents on topical delivery of NSAIDS (US 9012402 B1, US 9072659 B2, US 20150258196 A1) and patents indicating use of herbal penetration enhancers (US 20100273746A1, WO 2005009510 A2, US 6004969 A) helped in selecting the drug, excipients.
Current protocol employs various extracts of Piper cubeba fruit to evaluate its role in absorption of NPRS. Various batches containing 1% NPRS and varying concentrations of synthetic permeation enhancers or the extracts were formulated in carbopol gel. Gel was evaluated for parameters like organoleptic parameters, pH, viscosity and spreadability. An ex-vivo percutaneous absorption of NPRS from gel was investigated and compared with best performing synthetic enhancer, transcutol P (TP).
The batch containing 2% n-hexane extract (NHE) of Piper cubeba showed higher permeation than TP and Chloroform (CE), Methanolic (ME) and aqueous (AE) extracts as well. It showed improved % cumulative release (85.09%) and flux (278.61μg/cm2.h), as compared to TP and other extracts. Histopathology indicated the formulation safer as compared to that with synthetic enhancer.
It suggests P. cubeba as effective and safer tool for transdermal delivery and acts as therapeutic facilitator for naproxen. GC-MS analysis indicates lignans & terpenes in NHE to which this permeation enhancement activity may be attributed.
药物经皮肤吸收可避免口服途径的许多副作用，如胃部刺激、恶心、全身毒性等，从而提高患者的依从性。萘普生钠（NPRS）是一种强效非甾体抗炎药。
本研究旨在开发和评估含有NPRS的凝胶制剂用于透皮给药，以减少副作用并提高患者依从性。关于非甾体抗炎药局部给药的专利（美国专利9012402 B1、美国专利9072659 B2、美国专利20150258196 A1）以及表明使用草药渗透促进剂的专利（美国专利20100273746A1、国际专利申请WO 2005009510 A2、美国专利6004969 A）有助于选择药物和辅料。
当前方案采用荜澄茄果实的各种提取物来评估其在NPRS吸收中的作用。将含有1% NPRS和不同浓度合成渗透促进剂或提取物的不同批次制剂制成卡波姆凝胶。对凝胶进行感官参数、pH值、粘度和铺展性等参数的评估。研究了NPRS从凝胶中的体外经皮吸收情况，并与性能最佳的合成促进剂二乙二醇单乙醚（TP）进行比较。
含有2%荜澄茄正己烷提取物（NHE）的批次显示出比TP以及氯仿提取物（CE）、甲醇提取物（ME）和水提取物（AE）更高的渗透率。与TP和其他提取物相比，它显示出更高的累积释放率（85.09%）和通量（278.61μg/cm2·h）。组织病理学表明该制剂与使用合成促进剂的制剂相比更安全。
这表明荜澄茄是透皮给药的有效且安全的工具，并且是萘普生的治疗促进剂。气相色谱 - 质谱分析表明NHE中存在木脂素和萜类化合物，这种渗透增强活性可能归因于此。
