MICROCRYSTAL FORMULATIONS OF ETOPOSIDE

本提案涉及水不溶性抗癌剂依托泊苷， 并利用微晶技术生产改进的静脉输液 制剂，一种具有更高生物利用度的改进口服制剂 和肌肉内或皮下的缓释制剂 行政管理。微晶技术是一种独特的传递系统 其中药物的细微水悬浮液被包裹在 微流态化制备磷脂。悬浮液是稳定的，不是 容易沉淀，可冷冻干燥，储存时间更长，需要 只有生理盐水才能在以后重建它。微晶的优点 配方是它避免了有毒的增溶剂，如吐温 80或多山梨酸酯(可在目前的依托泊苷制剂中找到)， 所有成分都是组织相容的，缓释制剂是 有可能在I.M.或者南加州大学。用药和口服法 化合物的生物利用度可以大大提高。这个 这项技术也适用于其他难溶的抗癌药物， 包括紫杉醇、紫杉醇和喜树碱。

This proposal relates to the water-insoluble anticancer agent, etoposide, and the use of Microcrystal Technology to produce an improved intravenous formulation, an improved oral formulation with increased bioavailability and a slow-release formulation for intramuscular or subcutaneous administration. The Microcrystal Technology is a unique delivery system in which a fine aqueous suspension of drug is encapsulated in phospholipids by microfluidization. The suspension is stable, does not precipitate readily and can be lyophilized for longer storage, requiring only saline to reconstitute it later. The advantages of the microcrystal formulation are that it avoids toxic solubilizing agents such as tween 80 or polysorbate (which is found in present formulations of etoposide), all components are tissue compatible, slow-release formulations are possible when i.m. or s.c. administration is used and oral bioavailability of compounds can be substantially increased. The Technology has applicability to other poorly soluble anticancer agents, including taxol, taxotere and camptothecin.