Nikolakakis Ioannis, Malamataris Stavros
Department of Pharmaceutical Technology, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece.
J Pharm Sci. 2014 May;103(5):1453-65. doi: 10.1002/jps.23919. Epub 2014 Mar 4.
The effects of surfactant type and content on the kinetics of emulsion reconstitution and release of drugs differing in lipophilicity from self-emulsifying microcrystalline cellulose pellets were studied. Furosemide and propranolol were the drugs, medium-chain triglyceride was the oil, and Cremophors ELP, RH40, and RH60 were the surfactants. Pellets were prepared by extrusion/spheronization with emulsions (75% water and 25%, w/w, oil/surfactant/drug). Stability of the emulsions was evaluated from changes in the back-scattered light, and re-emulsification and drug release from light transmittance and UV spectroscopy, respectively. Emulsion stability increased because of the incorporation of the drugs. Re-emulsification depended only on the surfactant content and was expressed by a simple power equation (Ra2 > 0.945, Q(2) > 0.752). Drug release was expressed by two biexponential equations (Ra2 > 0.989, Q(2) > 0.699 and Ra2 > 0.947, Q(2) > 0.693) implying initial burst and terminal slow release phase and by the linear form (Lineweaver-Burke) of Michaelis-Menten equation (Ra2 > 0.726, Q(2) > 0.397). Relationships exist between the rate constants of the equations describing emulsion reconstitution and drug release, for propranolol compositions (R(2) = 0.915), and for compositions of both drugs with less hydrophilic ELP and RH40 (R(2) = 0.511), and also, among dissolution efficiency, drug solubility in oil/surfactant, and emulsion reconstitution ability, indicating the importance of drug solubilization in oil/surfactant and re-emulsification ability on drug release.
研究了表面活性剂类型和含量对自乳化微晶纤维素微丸中不同亲脂性药物的乳液重构动力学及释放的影响。呋塞米和普萘洛尔为药物，中链甘油三酯为油相，聚氧乙烯蓖麻油ELP、RH40和RH60为表面活性剂。通过将乳液（75%水和25%，w/w，油/表面活性剂/药物）进行挤出/滚圆制备微丸。分别从背散射光的变化评估乳液稳定性，从透光率和紫外光谱评估再乳化及药物释放。药物的加入提高了乳液稳定性。再乳化仅取决于表面活性剂含量，可用简单幂方程表示（相关系数Ra2>0.945，Q(2)>0.752）。药物释放可用两个双指数方程表示（相关系数Ra2>0.989，Q(2)>0.699和Ra2>0.947，Q(2)>0.693），意味着初始突释和终末缓释阶段，也可用米氏方程的线性形式（Lineweaver-Burke）表示（相关系数Ra2>0.726，Q(2)>0.397）。描述普萘洛尔组合物乳液重构和药物释放的方程速率常数之间存在关系（R(2)=0.915），两种药物与亲水性较低的ELP和RH40的组合物之间也存在关系（R(2)=0.511），并且在溶出效率、药物在油/表面活性剂中的溶解度和乳液重构能力之间也存在关系，表明药物在油/表面活性剂中的增溶作用和再乳化能力对药物释放的重要性。
