Department of Pharmaceutical Sciences, Bologna University, Bologna, Italy.
J Pharm Pharmacol. 2010 Mar;62(3):305-9. doi: 10.1211/jpp.62.03.0003.
The aim of this study was to develop transdermal films based on hydroxypropylmethylcellulose with the purpose of improving transdermal permeation of chlorpromazine hydrochloride, an antipsychotic drug used to alleviate the symptoms and signs of psychosis.
Hydroxypropylmethylcellulose films were prepared and evaluated for their drug content, film thickness, residual water content and bioadhesive properties. In-vitro permeation experiments were performed in the absence and in the presence of permeation enhancers (oleic acid, polysorbate 80, or both) with the purpose of improving drug availability. Other formulative parameters, such as drug and plasticizer concentration and hydroxypropylmethylcellulose type, were investigated.
Both oleic acid and polysorbate 80 had significant effect on drug permeation with respect to the control formulation. In particular films containing a mixture of oleic acid and polysorbate 80 provided the best enhancement activity for chlorpromazine. Moreover, a decrease in propylene glycol or chlorpromazine content or an increase of hydroxypropylmethylcellulose viscosity provided lower cumulative amounts of drug permeated.
The results obtained confirm that chlorpromazine permeation can be easily modulated by varying the composition of hydroxypropylmethylcellulose-based films. These formulations could serve as candidates for transdermal delivery of antipsychotic drugs.
本研究旨在开发基于羟丙甲纤维素的透皮贴剂，以改善盐酸氯丙嗪（一种用于缓解精神病症状和体征的抗精神病药物）的经皮渗透。
制备羟丙甲纤维素膜并对其药物含量、膜厚度、残留水分含量和生物黏附性能进行评价。进行了体外渗透实验，在不存在和存在渗透增强剂（油酸、聚山梨酯 80 或两者的混合物）的情况下，以提高药物的可用性。还研究了其他制剂参数，如药物和增塑剂浓度以及羟丙甲纤维素类型。
油酸和聚山梨酯 80 对药物渗透相对于对照制剂均有显著影响。特别是含有油酸和聚山梨酯 80 混合物的薄膜为氯丙嗪提供了最佳的增强活性。此外，降低丙二醇或氯丙嗪的含量或增加羟丙甲纤维素的黏度会导致透过的药物累积量减少。
所得结果证实，通过改变基于羟丙甲纤维素的薄膜的组成，可以轻松调节氯丙嗪的渗透。这些制剂可作为抗精神病药物经皮给药的候选药物。
