Department of Pharmaceutics, Bombay College of Pharmacy, Sundernagar, Kalina, Santacruz East, Mumbai 400098, India.
AAPS PharmSciTech. 2009;10(3):985-92. doi: 10.1208/s12249-009-9287-1. Epub 2009 Jul 30.
The objective of the present investigation was to formulate solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for improving the dermal delivery of a local anesthetic agent lidocaine (LID). SLN and NLC were characterized for particle size distribution, polydispersity index, entrapment efficiency, X-ray powder diffraction pattern (XRD), thermal behavior by differential scanning colorimeter (DSC) and surface morphology by transmission electron microscopy (TEM). LID-loaded SLN and NLC were formulated into hydrogels for topical application. The in vitro permeation profiles of LID SLN gel, LID NLC gel, and a marketed LID formulation (Xylocaine gel) were evaluated by using guinea pig skin. The in vivo efficacy of LID SLN gel, LID NLC gel, and a marketed LID formulation (Xylocaine gel) gel was evaluated on guinea pig using pinprick test. LID SLN showed a particle size of 78.1 nm with a polydispersity index of 0.556, whereas LID NLC showed a particle size of 72.8 nm with a polydispersity index of 0.463. The entrapment efficiency of LID in both SLN and NLC was 97% and 95.9%, respectively. The TEM studies revealed the almost spherical nature of LID SLN and NLC formulations. The XRD and DSC studies of LID SLN suggested amorphization of drug in the carrier system. The SLN formulation was stable with respect to particle size, polydispersity, and entrapment efficiency for 6 months at 40 degrees C/75% relative humidity (RH). Negligible leakage was observed for the NLC formulation when stored for 1 month at 40 degrees C/75% RH. In vitro permeation studies indicated that LID SLN gel and LID NLC gel significantly sustained the LID release compared to that of Xylocaine gel. The in vivo efficacy results supported the results of the in vitro permeation studies wherein the LID SLN gel and LID NLC gel resulted in fivefold and sixfold increase in duration of anesthesia, respectively, compared to that of Xylocaine gel.
本研究的目的是制备固体脂质纳米粒（SLN）和纳米结构脂质载体（NLC），以改善局部麻醉剂利多卡因（LID）的经皮传递。SLN 和 NLC 的粒径分布、多分散指数、包封效率、X 射线粉末衍射图谱（XRD）、差示扫描量热仪（DSC）的热行为和透射电子显微镜（TEM）的表面形态进行了表征。将 LID 负载的 SLN 和 NLC 制成用于局部应用的水凝胶。通过使用豚鼠皮肤评估 LID SLN 凝胶、LID NLC 凝胶和市售 LID 制剂（Xylocaine 凝胶）的体外渗透曲线。通过刺痛试验评估 LID SLN 凝胶、LID NLC 凝胶和市售 LID 制剂（Xylocaine 凝胶）在豚鼠体内的疗效。LID SLN 的粒径为 78.1nm，多分散指数为 0.556，而 LID NLC 的粒径为 72.8nm，多分散指数为 0.463。LID 在 SLN 和 NLC 中的包封效率分别为 97%和 95.9%。TEM 研究表明 LID SLN 和 NLC 制剂具有近乎球形的性质。LID SLN 的 XRD 和 DSC 研究表明药物在载体系统中呈非晶态。SLN 制剂在 40°C/75%相对湿度（RH）下放置 6 个月时，粒径、多分散性和包封效率均稳定。NLC 制剂在 40°C/75%RH 下储存 1 个月时，几乎没有观察到泄漏。体外渗透研究表明，与 Xylocaine 凝胶相比，LID SLN 凝胶和 LID NLC 凝胶显著延长了 LID 的释放。体内疗效结果支持体外渗透研究的结果，与 Xylocaine 凝胶相比，LID SLN 凝胶和 LID NLC 凝胶使麻醉持续时间分别延长了五倍和六倍。
