Yoon X A, Burgess D J
Dept. Pharmaceutical Science, School of Pharmacy, University of Connecticut, Storrs 06269-2092, USA.
J Pharm Pharmacol. 1997 May;49(5):478-84. doi: 10.1111/j.2042-7158.1997.tb06827.x.
Excess surfactant present in emulsions can influence the rates of transport of incorporated drugs by micellar solubilization, alteration of the partitioning process and by drug-surfactant complexation. Cetyltrimethylammonium bromide (CTAB), a cationic surfactant was selected to investigate these phenomena as it forms relatively stable mineral oil-water (O-W) emulsions and has the potential for ionic interaction. Phenylazoaniline, benzocaine, benzoic acid and phenol were chosen as model drugs for this study. The emulsion critical micelle concentration (CMC) for CTAB determined using a combination of a membrane equilibrium technique and surface-tension measurement was 1.0% w/v in 10% v/v% O-W emulsion systems. Ionic interaction between model drugs and surfactants and drug hydrophobicity affected their transport rates in the emulsion systems. The transport rates of the lipophilic drugs (benzocaine and phenylazoaniline) and the ionized hydrophillic drug (benzoic acid, pH 7.0) in the emulsion systems increased with increasing CTAB concentration up to 0.5% w/v micellar concentration and then decreased at higher concentrations. The rate of transport of phenol was not affected by the presence of micellar phase. Ionic interaction between surfactant and model drugs affected transport rates of model drugs in emulsion systems. The micellar phase was considered to affect the overall transport rates of model drugs.
乳剂中存在的过量表面活性剂可通过胶束增溶、分配过程的改变以及药物 - 表面活性剂络合作用来影响包封药物的转运速率。选择阳离子表面活性剂十六烷基三甲基溴化铵(CTAB)来研究这些现象,因为它能形成相对稳定的矿物油 - 水(O - W)乳剂,并且具有发生离子相互作用的潜力。本研究选择苯基偶氮苯胺、苯佐卡因、苯甲酸和苯酚作为模型药物。采用膜平衡技术和表面张力测量相结合的方法测定,在10% v/v% 的O - W乳剂体系中,CTAB的乳剂临界胶束浓度(CMC)为1.0% w/v。模型药物与表面活性剂之间的离子相互作用以及药物疏水性影响了它们在乳剂体系中的转运速率。在乳剂体系中,亲脂性药物(苯佐卡因和苯基偶氮苯胺)以及离子化的亲水性药物(苯甲酸,pH 7.0)的转运速率随着CTAB浓度增加至0.5% w/v胶束浓度而升高,然后在更高浓度时下降。苯酚的转运速率不受胶束相存在的影响。表面活性剂与模型药物之间的离子相互作用影响了模型药物在乳剂体系中的转运速率。胶束相被认为会影响模型药物的整体转运速率。