Malcolmson Carole, Barlow David J, Lawrence M Jayne
Department of Pharmacy, Franklin Wilkins Building, King's College London, 150 Stamford Street, London, SE1 9NN, United Kingdom.
J Pharm Sci. 2002 Nov;91(11):2317-31. doi: 10.1002/jps.10221.
Total-intensity light scattering (TILS) and photon correlation spectroscopy (PCS) techniques have been used to determine the droplet size of concentrated, oil-in-water microemulsions formed from soybean oil, polyoxyethylene-10-oleyl ether (C(18:1)E(10)), and water, both in the presence and absence of the lipophilic drug, testosterone enanthate. The TILS data were analyzed using the hard-sphere model of Percus-Yevick to account for interparticulate interactions experienced in the concentrated systems studied and the volume fraction of the hard-sphere droplet obtained from these analyses used to correct the PCS data. Correction of the light-scattering data in this manner yielded a satisfactory agreement between the size of the microemulsion droplets calculated using both techniques. Both the TILS and PCS data showed that, for a constant surfactant concentration, the size of the microemulsion droplets increased with increasing oil content. For example, droplets of radius 52.5 and 65.1 A (as determined by TILS) were obtained at 10.0% w/w C(18:1)E(10) and 0.5 and 2.0% w/w soybean oil, respectively. In contrast, for a constant oil concentration, microemulsion droplet size decreased with increasing surfactant concentration. For example, droplet sizes of 65.1, 59.3, 56.6, 54.5, and 53.3 A were seen with 2.0% w/w soybean oil and 10, 14.0, 18, 22, or 26% w/w C(18:1)E(10), respectively. Furthermore, in the presence of 1.0% w/w of the lipophilic drug, testosterone enanthate, the size of the microemulsion droplet increased by about 6-10 A depending on the concentration of the surfactant; the higher the concentration of the surfactant, the smaller the increase in size. The slight increase in size of the drug-containing microemulsion droplets suggests that some of the drug has penetrated into the core of the droplet.
总强度光散射(TILS)和光子相关光谱(PCS)技术已被用于测定由大豆油、聚氧乙烯-10-油基醚(C(18:1)E(10))和水形成的浓缩水包油微乳液的液滴大小,这一过程分别在有和亲脂性药物庚酸睾酮存在与不存在的情况下进行。使用Percus-Yevick硬球模型分析TILS数据,以解释在所研究的浓缩体系中颗粒间的相互作用,并将通过这些分析获得的硬球液滴的体积分数用于校正PCS数据。以这种方式对光散射数据进行校正后,两种技术计算得到的微乳液液滴大小之间达成了令人满意的一致性。TILS和PCS数据均表明,在表面活性剂浓度恒定的情况下,微乳液液滴的大小随油含量的增加而增大。例如,在10.0% w/w C(18:1)E(10)以及0.5%和2.0% w/w大豆油的条件下,通过TILS测定得到的液滴半径分别为52.5 Å和65.1 Å。相反,在油浓度恒定的情况下,微乳液液滴大小随表面活性剂浓度的增加而减小。例如,在2.0% w/w大豆油以及10%、14.0%、18%、22%或26% w/w C(18:1)E(10)的条件下,观察到的液滴大小分别为65.1 Å、59.3 Å、56.6 Å、54.5 Å和53.3 Å。此外,在存在1.0% w/w亲脂性药物庚酸睾酮的情况下,微乳液液滴的大小根据表面活性剂浓度增加约6 - 10 Å;表面活性剂浓度越高,大小增加越小。含药微乳液液滴大小的轻微增加表明部分药物已渗透到液滴核心。