Opawale F O, Burgess D J
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs 06269, USA.
J Pharm Pharmacol. 1998 Sep;50(9):965-73. doi: 10.1111/j.2042-7158.1998.tb06910.x.
The purpose of this study was to investigate the influence of mixtures of the emulsifiers Span 80, 83 and 85 and Tween 80 on multiple emulsion stability. An oscillatory ring-surface rheometer was used to measure interfacial elasticity at the oil-aqueous interface. Multiple emulsions were prepared via a two-step emulsification process and stability was evaluated by investigation of drug transport from freshly prepared and eight-day-old emulsions by use of a dialysis method. Photomicrography and droplet-size analysis of multiple emulsions were also conducted. Spans 80 and 83 were appreciably elastic (683.10+/-29.13 mNm(-1) and 1128.09+/-14.81 mNm(-1), respectively at 5% w/v) when present at the mineral oil-aqueous interface whereas Span 85 and Tween 80 were not (11.10+/-3.88 mNm(-1) (5% w/v) and 0 (0.1-5% w/v) respectively). The interfacial elasticities of Spans 80 and 83 decreased in the presence of Tween 80 in the aqueous phase; this was attributed to co-adsorption of Tween 80 at the interface or aqueous-phase solubilization of the Spans within mixed micelles, or both. Drug-transport studies indicated that drug release on storage was lower from water-in-oil-in-water (w/o/w) emulsions prepared with 5% w/v Span 80 or 83 and 0.1% w/v Tween 80 than from emulsions prepared with 5% w/v Spans 80 or 83 and 1% w/v Tween 80. Photomicrography and droplet-size analysis indicated the same trend-emulsions containing a higher percentage of Tween 80 were less stable. The relatively stable w/o/w emulsions (e.g. 5% w/v Spans 80 or 83 and 0.1% w/v Tween 80) contained a large number of multiple droplets for up to eight weeks of storage whereas the relatively unstable w/o/w emulsions (e.g., 5% w/v Span 85 and 0.1% w/v Tween 80 and 5% w/v Spans and 1% w/v Tween 80) contained mostly simple droplets after only one week of storage. The mean volume/weight droplet size decreased on storage with breakdown of these w/o/w emulsions to simple oil-in-water emulsions. There was a positive correlation between the interfacial elasticity and emulsion stability data. Mixed emulsifiers giving higher film strength, as quantified by interfacial elasticity measurements, resulted in more stable w/o/w emulsions.
本研究的目的是考察乳化剂司盘80、83、85与吐温80的混合物对复乳稳定性的影响。使用振荡环表面流变仪测量油-水界面的界面弹性。通过两步乳化法制备复乳,并采用透析法研究新鲜制备的和保存八天的乳液中药物的转运情况,以此评估复乳的稳定性。还对复乳进行了显微摄影和液滴尺寸分析。当司盘80和83存在于矿物油-水界面时具有明显的弹性(5% w/v时分别为683.10±29.13 mN/m和1128.09±14.81 mN/m),而司盘85和吐温80则没有(5% w/v时司盘85为11.10±3.88 mN/m,0.1 - 5% w/v时吐温80为0)。在水相中存在吐温80时,司盘80和83的界面弹性降低;这归因于吐温80在界面处的共吸附或司盘在混合胶束中的水相增溶作用,或两者皆有。药物转运研究表明,与用5% w/v司盘80或83和1% w/v吐温80制备的乳液相比,用5% w/v司盘80或83和0.1% w/v吐温80制备的水包油包水(w/o/w)型乳液在储存时药物释放较低。显微摄影和液滴尺寸分析表明了相同的趋势——含有较高百分比吐温80的乳液稳定性较差。相对稳定的w/o/w型乳液(如5% w/v司盘80或83和0.1% w/v吐温80)在储存长达八周的时间内含有大量的多重液滴,而相对不稳定的w/o/w型乳液(如5% w/v司盘85和0.1% w/v吐温80以及5% w/v司盘和1% w/v吐温80)在储存仅一周后大多含有简单液滴。随着这些w/o/w型乳液分解为简单的水包油型乳液,储存过程中液滴的平均体积/重量尺寸减小。界面弹性与乳液稳定性数据之间存在正相关。通过界面弹性测量量化得出,具有较高膜强度的混合乳化剂可形成更稳定的w/o/w型乳液。