Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, 27-31 Joan XXIII Av,, 08028, Barcelona,, Spain.
Nanoscience and Nanotechnology Institute (IN2UB), University of Barcelona, 27-31 Joan XXIII Av, 08028, Barcelona, Spain.
Pharm Res. 2017 Aug;34(8):1728-1740. doi: 10.1007/s11095-017-2181-8. Epub 2017 May 24.
In order to obtain dermal vehicles of ketorolac tromethamine (KT) for the local treatment of inflammation and restrict undesirable side effects of systemic levels hydrogels (HGs) of poloxamer and carbomer were developed.
KT poloxamer based HG (KT-P407-HG) and KT carbomer based HG (KT-C940-HG) were elaborated and characterized in terms of swelling, degradation, porosity, rheology, stability, in vitro release, ex vivo permeation and distribution skin layers. Finally, in vivo anti-inflammatory efficacy and skin tolerance were also assessed.
HGs were transparent and kept stable after 3 months exhibiting biocompatible near neutral pH values. Rheological patterns fitted to Herschel-Bulkley for KT-C940-HG and Newton for KT-P407-HG due to its low viscosity at 25°C. Rapid release profiles were observed through first order kinetics. Following the surface the highest concentration of KT from C940-HG was found in the epidermis and the stratum corneum for P407-HG. Relevant anti-inflammatory efficacy of KT-P407-HG revealed enough ability to provide sufficient bioavailability KT to reach easily the site of action. The application of developed formulations in volunteers did not induce any visual skin irritation.
KT-P407-HG was proposed as suitable formulation for anti-inflammatory local treatment without theoretical systemic side effect.
为了获得酮咯酸氨丁三醇（KT）的透皮制剂，用于局部治疗炎症，并限制全身水平的聚氧丙烯和卡波姆水凝胶（HGs）的不良副作用。
研制了基于聚氧丙烯的 KT 水凝胶（KT-P407-HG）和基于卡波姆的 KT 水凝胶（KT-C940-HG），并对其溶胀、降解、孔隙率、流变学、稳定性、体外释放、体外渗透和分布皮肤层进行了表征。最后，还评估了体内抗炎功效和皮肤耐受性。
HGs 在 3 个月后仍保持透明且稳定，表现出生物相容性和接近中性的 pH 值。流变学模式适合于 Herschel-Bulkley 用于 KT-C940-HG 和 Newton 用于 KT-P407-HG，因为其在 25°C 时粘度较低。通过一级动力学观察到快速释放曲线。从表面看，C940-HG 中 KT 的最高浓度出现在表皮和角质层，而 P407-HG 中 KT 的最高浓度出现在表皮和角质层。KT-P407-HG 的相关抗炎功效表明，它有足够的能力提供足够的 KT 生物利用度，使其容易到达作用部位。在志愿者中应用所开发的制剂不会引起任何视觉皮肤刺激。
KT-P407-HG 被提议作为一种适合局部抗炎治疗的制剂，没有理论上的全身副作用。
