Samczewska Grazyna
Zakad Farmacji Aptecznej, Katedra Farmacji Stosowanej Uniwersytet Medyczny w Łodzi.
Polim Med. 2009;39(4):25-37.
In the second half of the 20th century a heterogenic group of opioid receptors was discovered and identified in the central nervous system and in peripheral tissues. However, micro-type opioid receptors, responsible for analgesic effect of endogenic and egzogenic opioids, were not found on majority of peripheral neurons. They appear in skin or mucous membranes with active inflammatory or neoplastic process due to intensive migration to peripheral nerve efferent fibres. These discoveries made it possible to apply opioid analgesics topically (ointments, hydrogels) on pathologically changed skin or mucous membranes. This study presents the results of tests on two batches of hydrogel preparations produced according to own prescription on the base of acrylic acid polymers (Carbopol Ultrez 10 and Carbopol 980 NF). The polymer carboxyl groups were neutralized with different bases: sodium hydroxide, potasium hydroxide, triethanolamine, sodium tetraborate. The obtained hydrogel preparations were subjected to rheological tests. Extensibility was determined by extensometric method, whereas viscosity, yield stress and thixotropy were determined with the use of cone-plate digital rheometer. The activity of hydrogels hydrogen ions (pH) and the rate of their loss of volatile components at human body temperature were also tested. Using modified Mutimer apparatus morphine hydrochloride (MCl) diffusion was performed from the surface of the produced hydrogels through model stratum corneum (Tomofan) to acceptor fluid (water). The quantity of the released therapeutic agent in time function was determined by spectrophotometric method. The carried out studies have demonstrated that the produced hydrogels are non-Newtonian, viscoelastic, thixotropic systems of similar yield stress. The obtained results do not allow to determine unequivocally the effect of MCl, the kind of Carbopol and cross-linking base on hydrogel viscosity. The inversely proportional dependence between hydrogel viscosity (eta) and theoretical diffusion coefficient (D) of morphine hydrochloride was not observed, either. The loss of volatile components (water) is more effective from hydrogels produced on Carbopol Ultrez 10 base. The process of MCl diffusion is most effective from hydrogel made on Carbopol Ultrez 10 base and neutralized with sodium hydroxide or triethanolamine.
20世纪下半叶,在中枢神经系统和外周组织中发现并鉴定出一组异质性阿片受体。然而,负责内源性和外源性阿片类药物镇痛作用的微型阿片受体在大多数外周神经元上并未发现。它们出现在具有活跃炎症或肿瘤过程的皮肤或黏膜中,这是由于它们大量迁移到外周神经传出纤维所致。这些发现使得在病理改变的皮肤或黏膜上局部应用阿片类镇痛药(软膏、水凝胶)成为可能。本研究展示了根据自身配方以丙烯酸聚合物(卡波姆Ultrez 10和卡波姆980 NF)为基础生产的两批水凝胶制剂的测试结果。聚合物羧基用不同的碱进行中和:氢氧化钠、氢氧化钾、三乙醇胺、硼砂。对获得的水凝胶制剂进行流变学测试。拉伸性通过引伸计法测定,而粘度、屈服应力和触变性则使用锥板数字流变仪测定。还测试了水凝胶氢离子的活性(pH值)及其在人体温度下挥发性成分的损失率。使用改良的穆蒂默仪器,使盐酸吗啡(MCl)从所生产水凝胶的表面通过模型角质层(托莫凡)扩散到接受液(水)中。通过分光光度法测定释放的治疗剂随时间的量。所进行的研究表明,所生产的水凝胶是非牛顿、粘弹性、触变性的系统,屈服应力相似。所获得的结果无法明确确定MCl、卡波姆种类和交联碱对水凝胶粘度的影响。也未观察到水凝胶粘度(η)与盐酸吗啡理论扩散系数(D)之间的反比关系。基于卡波姆Ultrez 10制成的水凝胶中挥发性成分(水)的损失更有效。MCl从基于卡波姆Ultrez 10制成并用氢氧化钠或三乙醇胺中和的水凝胶中的扩散过程最有效。