Ahn B N, Kim S K, Shim C K
Department of Pharmaceutics, College of Pharmacy, Seoul National University, Korea.
J Microencapsul. 1995 Jul-Aug;12(4):363-75. doi: 10.3109/02652049509087249.
Proliposomes were prepared by the penetration of a methanol-chloroform solution of propranolol hydrochloride (PH) and lecithin into microporous sorbitol, with subsequent vacuum drying. They were characterized for surface morphology and flowability, and following the conversion to liposomes upon hydration, size distribution, drug content and in vitro drug release of the reconstituted liposomes were examined. The porous structure of sorbitol was maintained in the proliposomes, affording the proliposomes good flowability at lecithin-to-sorbitol ratios (w/w) of not more than 0.2. Multilamellar liposomes were reconstituted spontaneously from the proliposomes upon hydration. The mean diameter of the resultant liposomes was highly dependent on the PH-to-lecithin ratio, but less dependent on the lecithin-to-sorbitol ratio and sorbitol particle size (105-710 microns). Entrapment efficiency of PH in liposomes showed a maximum 10% at PH-to-lecithin ratio < 0.5 and a lecithin-to-sorbitol ratio > 0.1. Sustained release of propranolol from the proliposomes was achieved when the lecithin-to-PH ratio was > 2, and the lecithin-to-sorbitol ratio was in the range examined (0.067-0.2). In conclusion, granular proliposomes of PH with good flowability and sustained release characteristics could be prepared by controlling the drug/lecithin/sorbitol ratio and sorbitol particle size. PH proliposomes can be potential candidates for the sustained drug delivery of propranolol when applied directly onto the mucosal membranes.
通过将盐酸普萘洛尔（PH）和卵磷脂的甲醇 - 氯仿溶液渗透到微孔山梨醇中，随后进行真空干燥来制备前体脂质体。对其表面形态和流动性进行了表征，并且在水合后转化为脂质体后，检查了重构脂质体的大小分布、药物含量和体外药物释放情况。山梨醇的多孔结构在前体脂质体中得以保留，在卵磷脂与山梨醇的比例（w/w）不超过0.2时，赋予前体脂质体良好的流动性。水合后，多层脂质体从前体脂质体中自发重构。所得脂质体的平均直径高度依赖于PH与卵磷脂的比例，但对卵磷脂与山梨醇的比例和山梨醇粒径（105 - 710微米）的依赖性较小。当PH与卵磷脂的比例<0.5且卵磷脂与山梨醇的比例>0.1时，脂质体中PH的包封率最高可达10%。当卵磷脂与PH的比例>2且卵磷脂与山梨醇的比例在所研究的范围内（0.067 - 0.2）时，前体脂质体实现了普萘洛尔的持续释放。总之，通过控制药物/卵磷脂/山梨醇比例和山梨醇粒径，可以制备具有良好流动性和持续释放特性的PH颗粒状前体脂质体。当直接应用于粘膜时，PH前体脂质体可能是普萘洛尔持续药物递送的潜在候选物。
