A-sasutjarit Rathapon, Sirivat Anuvat, Vayumhasuwan Panida
Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Pharm Res. 2005 Dec;22(12):2134-40. doi: 10.1007/s11095-005-8244-2. Epub 2005 Oct 14.
This study was conducted to determine the effect of formula compositions on viscoelastic properties of piroxicam gels using Carbopol 940 as a gelling agent and to determine the relationships between viscoelastic properties of Carbopol 940 gel bases and diffusion coefficients of piroxicam in gel bases.
Piroxicam gels (1.0% w/w) were prepared by using Carbopol 940 as a gelling agent and varying Carbopol 940 concentrations, glycerin, and sodium chloride contents. The in vitro release of piroxicam from gel bases to the receiving media, isotonic phosphate buffer solution (pH 7.4), were carried out using Franz-modified cell. The piroxicam diffusion coefficients were obtained by Higuchi's equation. Rheological property measurements of gel samples were performed via a cone and plate fluid rheometer. Relationships between viscoelastic properties of gel samples and piroxicam diffusion in gel bases were analyzed by Pearson's test at a p value of less than 0.05.
All piroxicam gels exhibited predominantly elastic solid behavior whose magnitude depended on Carbopol 940 concentration. Preparations containing good solvent exhibited more elastic solid characters. In contrast, the piroxicam gels containing higher sodium chloride contents possessed more viscous fluid behavior. Analyzed by Pearson's test at a p value of less than 0.05, piroxicam diffusion coefficients were directly proportional to loss tangent, but were inversely proportional to storage modulus, loss modulus, complex modulus, and viscosity.
There is a potential for predicting drug diffusion coefficients from their correlations to rheological parameters. This could be beneficial to the formulation design of transdermal drug delivery systems including mucoadhesive drug delivery systems.
本研究旨在确定以卡波姆940作为凝胶剂时，配方组成对吡罗昔康凝胶黏弹性的影响，并确定卡波姆940凝胶基质的黏弹性与吡罗昔康在凝胶基质中扩散系数之间的关系。
以卡波姆940作为凝胶剂，改变卡波姆940浓度、甘油和氯化钠含量，制备1.0%（w/w）的吡罗昔康凝胶。使用Franz改良细胞，将吡罗昔康从凝胶基质释放到接收介质（等渗磷酸盐缓冲溶液，pH 7.4）中进行体外释放实验。通过Higuchi方程获得吡罗昔康的扩散系数。通过锥板流体流变仪对凝胶样品进行流变学性质测量。在p值小于0.05的情况下，通过Pearson检验分析凝胶样品的黏弹性与吡罗昔康在凝胶基质中扩散之间的关系。
所有吡罗昔康凝胶主要表现出弹性固体行为，其程度取决于卡波姆940的浓度。含有良溶剂的制剂表现出更多的弹性固体特征。相反，含有较高氯化钠含量的吡罗昔康凝胶具有更多的黏性流体行为。在p值小于0.05的情况下通过Pearson检验分析，吡罗昔康扩散系数与损耗角正切成正比，但与储能模量、损耗模量、复数模量和黏度成反比。
根据药物与流变学参数的相关性预测药物扩散系数具有潜力。这可能有利于包括黏膜黏附给药系统在内的透皮给药系统的制剂设计。
