目的 研究地氯雷他定（DL）自微乳的制劑處方與制備工藝，并對(duì)其質(zhì)量進(jìn)行評(píng)價(jià)。方法 通過溶解度實(shí)驗(yàn)，偽三元相圖實(shí)驗(yàn)，油相、乳化劑及助乳化劑配伍實(shí)驗(yàn)，篩選出DL自微乳制劑的處方組成；以乳滴平均粒徑，載藥量及包封率為指標(biāo)，采用單純形網(wǎng)格法優(yōu)化制劑處方，并對(duì)DL自微乳的理化性質(zhì)，溶出度以及穩(wěn)定性進(jìn)行評(píng)價(jià)。結(jié)果 DL自微乳處方中油相為中碳鏈三甘酯（MCT）（35%），乳化劑為聚乙二醇-12羥基-硬脂酸酯（HS15）（45%），助乳化劑為1，2-丙二醇（20%）。所得自微乳制劑外觀均一透明，略帶黏性，自乳化后平均粒徑為20.21 nm，平均載藥量為20.95 mg/g，包封率為76.56%。溶出度實(shí)驗(yàn)結(jié)果表明，DL 60 min累積溶出率達(dá)到93.78%。穩(wěn)定性實(shí)驗(yàn)表明，高溫、光照影響自微乳制劑的穩(wěn)定性，制劑應(yīng)低溫避光保存。結(jié)論 DL自微乳制劑制備工藝簡單，質(zhì)量穩(wěn)定，能顯著增加藥物的溶解度，進(jìn)而提高DL的口服生物利用度。

Objective to study the formulation, preparation and quality evaluation of DL self-microemulsion preparation. Methods through solubility test, pseudo-ternary phase diagram test, oil phase, emulsifier and co-emulsifier compatibility test, the formulation of DL self-microemulsion preparation was screened out. Through particle size determination, drug loading and encapsulation rate determination, simplex mesh method was used to optimize the formulation, and the physical and chemical properties, dissolution and stability of self-microemulsion preparation of DL were evaluated. Results the oil phase of DL from the formulation of microemulsion was medium c-triglyceride (MCT) (35%), (HS15) (45%), and 1, 2-propylene glycol (20%). The dissolution test results showed that DL accumulated dissolution rate reached 93.85% after 60min. The stability experiment shows that low temperature, high temperature, high humidity and illumination all affect the stability of self-microemulsion preparation, so the preparation should be kept dry in room temperature away from light. Conclusion the preparation process of DL self-microemulsion preparation is simple, the excient components are low toxic and the quality of the preparation is stable, which can significantly increase the solubility of the drug, thus improving the oral bioavailability of DL. It provides reference for the further research and development about the related preparations of this drug.

R944

國家“十三五”重大科技專項(xiàng)（2017ZX09101002-001-005）