Ochoa-Andrade Ana, Parente M Emma, Jimenez-Kairuz Álvaro, Boinbaser Lucía, Torregrosa Annibal
Pharmaceutical Technology, Department of Pharmaceutical Sciences, Facultad de Química, Universidad de la República, Gral. Flores 2124, 11800, Montevideo, Uruguay.
Cosmetic Chemistry, Department of Pharmaceutical Sciences, Facultad de Química, Universidad de la República, Montevideo, Uruguay.
AAPS PharmSciTech. 2017 Aug;18(6):2269-2278. doi: 10.1208/s12249-016-0707-8. Epub 2017 Jan 17.
The aim of the present work was to study the main formulation variables that influence attributes of bioadhesive emulgels based on a combination of polymers, using response surface methodology (RSM). Bioadhesive products continue to gain attention in topical cutaneous administration as they allow long residence times on the application site, which is important when a long dermal action and a reduced product administration frequency are desired. A Box-Behnken design of experiments (DoE) was introduced to study the effect of formulation variables on quality attributes of the emulgels. The effects of concentration of carbomer interpolymer type A (Polym1), xanthan gum (Polym2) and mineral oil (Oil) on detachment force (Fdetch), spreadability (Spread), and phase separation by mechanical stress (PhSep) were investigated. RSM and desirability functions were applied for data analysis. Emulgels were further characterized by viscosity and extrudability measurements. Polym1 showed a positive effect on Fdetch, while the increase in concentrations of Polym2 and Oil decreased this property. Polym1 and Polym2 favored emulgel PhSep. However, their interaction effect decreased it. The combination of 0.4-0.6% of carbomer and 0.2-0.3% of gum was able to produce easy-to-spread bioadhesive emulgels with mineral oil as discontinuous phase in the presence of a low surfactant concentration. Based on the DoE results, value ranges for the variables, which could achieve for the experimental domain to get the critical quality attributes of emulgels jointly within the specification limits, were able to be identified using RSM supported by desirability functions.
本研究的目的是使用响应面法（RSM）研究影响基于聚合物组合的生物粘附性乳胶凝胶属性的主要配方变量。生物粘附性产品在局部皮肤给药中持续受到关注，因为它们能够在应用部位长时间停留，这在期望长期皮肤作用和减少产品给药频率时很重要。引入了Box-Behnken实验设计（DoE）来研究配方变量对乳胶凝胶质量属性的影响。研究了A型卡波姆共聚物（Polym1）、黄原胶（Polym2）和矿物油（Oil）的浓度对剥离力（Fdetch）、铺展性（Spread）和机械应力引起的相分离（PhSep）的影响。应用RSM和期望函数进行数据分析。通过粘度和挤出性测量对乳胶凝胶进行了进一步表征。Polym1对Fdetch有积极影响，而Polym2和Oil浓度的增加则降低了该性能。Polym1和Polym2有利于乳胶凝胶的PhSep。然而，它们的相互作用效应降低了PhSep。在低表面活性剂浓度下，0.4 - 0.6%的卡波姆和0.2 - 0.3%的胶的组合能够生产出以矿物油为分散相、易于铺展的生物粘附性乳胶凝胶。基于DoE结果，使用由期望函数支持的RSM能够确定变量的值范围，该范围在实验域内可实现，以使乳胶凝胶的关键质量属性共同在规格限度内。
