环丙沙星缓释微粒制剂的研制
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摘要
目的：采用现代制药技术，制备环丙沙星缓释微粒制剂，为动物保健提供一种安全、高效、方便的新剂型药物。
内容与方法：以环丙沙星为主药，分别用液中干燥法和W／O微乳法制备了乙基纤维素载药毫微粒和明胶微粒，以粒径、形状、包封率等为评价指标，通过单因素考察及多因素的正交实验设计进行工艺条件和处方的优化；通过对单一微粒和复合微粒进行体外释放度实验，筛选出两种微粒及原药的最佳混合比例；进行抑菌实验和急性毒性实验，评价其体外抗菌活性和体内安全性；进行家兔体内药动学实验，评定其体内药效性。
结果：工艺优化后所制乙基纤维素毫微粒平均粒径为680nm，载药量=18.2％，包封率=84.5％，15天后在体外释放达到90％左右；所制明胶微粒的平均粒径为4.5um，载药量为19.2％，包封率为89％，3天后在体外释放可达到80％以上；根据二者特点的差异，将毫微粒、微粒、原料药按2：4：1的比例混合制成的缓释制剂经测定，100h后体外释放率达到约90％，达到较理想的缓释效果；在急性毒性实验中，该缓释微粒毒性很低，对小鼠的最大给药量是9500mg／kg；通过抑菌实验，证实了所制毫微粒的长效抗菌活性；缓释微粒制剂在家兔体内的t_(1／2)(Ke)为23.9h，相对生物利用度为119.4％，分别约是原药的6倍和2倍。
结论：本研究制备的缓释微粒物理性能好，体内释放平稳，生物利用度高，具有明显的缓释控释效果，有望开发为环丙沙星的一种新制剂。
Object: Prepararing of Ciprofloxacin sustained release formulation with mordenpharmacy technique, offering a safety,high efficiency and convenient new dosageform for health care of Animals.
Content and Methods: Making ciprofloxacin material, to prepare Ethyl Cellulosenanoparticles by the way of evaporation from liquor and Gelatin microspheres in W/O microemulsion. Research the prescription and acertain the main influencing factors;characterized in terms of morphology,size,encapsulation efficiency,etc.comparingsingle microparticles and complex microparticles in vitro drug release,then screensizing the best mixing ratio among EC nanoparticles,GL microspheres andciprofloxacin; Progression of bacteriostasis experiment in vitro and acute toxicity test,evaluating antibacterial activity in vitro and security in vivo; researched preliminarythe Ciprofloxacin sustained release medication's security and pharmacokinetics inrabbits.
Results: The EC nanoparticles prepared with the optimized method had a mean diameterof 680nm,a drug content of 18.2％, and an enveloping rate of 84.5％. 90％of the drug wasreleased in 15d;The gelatine microspheres prepared with the optimized method had amean diameter of 4.Sum,the drug loading and enveloping rate were 19.2％and 89％, abave80％of the drug was released in 3d; the best complex sustaind release formulation wascomposed of EC nanoparticles, GL microspheres and ciprofloxacin, their rate was 2:4:1;after 100 hours, about 90％of the drug was released from the complex sustained releaseformulation; at the later period of the staphylococcal bacteria bacteriostasis experiment invitro, EC nanoparticles showed the controlled release antibacterial activity;themicroparticles' toxicity was very low, and the biggest dosage was 9500mg/kg in the acutetoxicity test for mouses; The T_(1/2)(Ke) of the sustained release medication was 23.9h inrabbits, it is sixfold as much as ciprofloxacin; the biocompatibility was 119.4％andtwofold as much as ciprofloxacin.
Conclusion: The Ciprofloxacin complex sustained release medication showedsignificant sustained release effect, it was safety and innocuity for animals at the doserange. We hope exploit it as a new sustained release formulation.
内容与方法：以环丙沙星为主药，分别用液中干燥法和W／O微乳法制备了乙基纤维素载药毫微粒和明胶微粒，以粒径、形状、包封率等为评价指标，通过单因素考察及多因素的正交实验设计进行工艺条件和处方的优化；通过对单一微粒和复合微粒进行体外释放度实验，筛选出两种微粒及原药的最佳混合比例；进行抑菌实验和急性毒性实验，评价其体外抗菌活性和体内安全性；进行家兔体内药动学实验，评定其体内药效性。
结果：工艺优化后所制乙基纤维素毫微粒平均粒径为680nm，载药量=18.2％，包封率=84.5％，15天后在体外释放达到90％左右；所制明胶微粒的平均粒径为4.5um，载药量为19.2％，包封率为89％，3天后在体外释放可达到80％以上；根据二者特点的差异，将毫微粒、微粒、原料药按2：4：1的比例混合制成的缓释制剂经测定，100h后体外释放率达到约90％，达到较理想的缓释效果；在急性毒性实验中，该缓释微粒毒性很低，对小鼠的最大给药量是9500mg／kg；通过抑菌实验，证实了所制毫微粒的长效抗菌活性；缓释微粒制剂在家兔体内的t_(1／2)(Ke)为23.9h，相对生物利用度为119.4％，分别约是原药的6倍和2倍。
结论：本研究制备的缓释微粒物理性能好，体内释放平稳，生物利用度高，具有明显的缓释控释效果，有望开发为环丙沙星的一种新制剂。
Object: Prepararing of Ciprofloxacin sustained release formulation with mordenpharmacy technique, offering a safety,high efficiency and convenient new dosageform for health care of Animals.
Content and Methods: Making ciprofloxacin material, to prepare Ethyl Cellulosenanoparticles by the way of evaporation from liquor and Gelatin microspheres in W/O microemulsion. Research the prescription and acertain the main influencing factors;characterized in terms of morphology,size,encapsulation efficiency,etc.comparingsingle microparticles and complex microparticles in vitro drug release,then screensizing the best mixing ratio among EC nanoparticles,GL microspheres andciprofloxacin; Progression of bacteriostasis experiment in vitro and acute toxicity test,evaluating antibacterial activity in vitro and security in vivo; researched preliminarythe Ciprofloxacin sustained release medication's security and pharmacokinetics inrabbits.
Results: The EC nanoparticles prepared with the optimized method had a mean diameterof 680nm,a drug content of 18.2％, and an enveloping rate of 84.5％. 90％of the drug wasreleased in 15d;The gelatine microspheres prepared with the optimized method had amean diameter of 4.Sum,the drug loading and enveloping rate were 19.2％and 89％, abave80％of the drug was released in 3d; the best complex sustaind release formulation wascomposed of EC nanoparticles, GL microspheres and ciprofloxacin, their rate was 2:4:1;after 100 hours, about 90％of the drug was released from the complex sustained releaseformulation; at the later period of the staphylococcal bacteria bacteriostasis experiment invitro, EC nanoparticles showed the controlled release antibacterial activity;themicroparticles' toxicity was very low, and the biggest dosage was 9500mg/kg in the acutetoxicity test for mouses; The T_(1/2)(Ke) of the sustained release medication was 23.9h inrabbits, it is sixfold as much as ciprofloxacin; the biocompatibility was 119.4％andtwofold as much as ciprofloxacin.
Conclusion: The Ciprofloxacin complex sustained release medication showedsignificant sustained release effect, it was safety and innocuity for animals at the doserange. We hope exploit it as a new sustained release formulation.
引文
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