Institute of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, Belgrade Vojvode Stepe 450, 11221 Belgrade, Serbia.
Int J Pharm. 2009 Nov 3;381(2):220-30. doi: 10.1016/j.ijpharm.2009.07.007. Epub 2009 Jul 16.
This study focuses on the properties of topical vehicles based on alkylpolyglucoside natural surfactant-mixed emulsifier, cetearyl glucoside and cetearyl alcohol, in order to propose their use as "ready to use" pharmaceutical bases for a number of model drugs. We were interested to investigate how the alternative use of three lipophilic excipients (Ph. Eur. 6.0), differing in their polarity indexes (medium chain triglycerides (MG), decyl oleate (DO), and isopropyl myristate (IPM), respectively), affects the colloidal structure of the alkylpolyglucoside-based vehicles and in vitro permeation profiles of two model drugs: diclofenac sodium (DC) and caffeine (CF), both sparingly soluble in water. Finally, we aimed to evaluate the safety profile of such vehicles in vitro (acute skin irritation test using a cytotoxicity assay), comparing it with in vivo data obtained by the methods of skin bioengineering. The results have shown that the emulsion vehicles consisted of a complex colloidal structure of lamellar liquid crystalline and lamellar gel crystalline type. Varying of lipophilic excipient influenced noteworthy variations in the colloidal structure demonstrated as different rheological profiles accompanied to the certain degree by different water distribution modes, but notably provoked by drug nature (an amphiphilic electrolyte drug vs. nonelectrolyte). In vitro permeation data obtained using ASC membranes in an infinite dose-type of experiment stressed the importance of the vehicle/solute interactions in case of small variation in formulation composition, asserting the drug properties in the first hours of permeation and rheological profile of the vehicles in the later phase of experiment as decisive factors. In vitro skin irritation test demonstrated a mild nature of the emulsifying wax and the absence of negative effects of used oil phases on cell viability in formulation concentrations correspondent to the therapeutic need. This result alongside with data obtained from in vivo study, could additionally promote investigated topical vehicles as prospective "ready to use" pharmaceutical bases.
本研究集中于基于烷基聚葡糖苷天然表面活性剂-混合乳化剂、鲸蜡硬脂基葡糖苷和鲸蜡硬脂醇的局部用制剂的性质，以便提出将其用作多种模型药物的“即用型”药物制剂基质。我们有兴趣研究三种亲脂性赋形剂（欧洲药典 6.0）的替代用途如何影响基于烷基聚葡糖苷的制剂的胶体结构，这三种亲脂性赋形剂在极性指数方面有所不同（中链甘油三酯（MG）、癸酸油醇酯（DO）和肉豆蔻异丙酯（IPM）），以及两种模型药物（二氯芬酸钠（DC）和咖啡因（CF））的体外渗透特性，这两种药物在水中的溶解度都较低。最后，我们旨在评估此类制剂在体外的安全性概况（使用细胞毒性测定进行急性皮肤刺激性试验），并将其与通过皮肤生物工程方法获得的体内数据进行比较。结果表明，乳剂制剂由层状液晶和层状凝胶晶体型的复杂胶体结构组成。亲脂性赋形剂的变化会引起胶体结构的显著变化，表现为不同的流变学特性，伴随着一定程度上不同的水分分布模式，但主要是由药物性质（亲脂性电解质药物与非电解质药物）引起的。使用 ASC 膜在无限剂量型实验中获得的体外渗透数据强调了制剂组成小变化情况下制剂基质与溶质相互作用的重要性，在渗透的最初几个小时内强调了药物性质的重要性，而在实验的后期阶段，制剂基质的流变学特性则起决定性作用。体外皮肤刺激性试验表明乳化蜡具有温和的性质，并且在制剂浓度下使用的油相对细胞活力没有负面影响，该浓度对应于治疗需要。这一结果与体内研究获得的数据一起，可以进一步促进所研究的局部用制剂作为有前途的“即用型”药物制剂基质。
