目的 制备扎西他宾微孔渗透泵控释片和单室渗透泵控释片。方法 建立了释放度测定方法,通过单因素实验确定促渗透活性物质的用量、致孔剂PEG400的用量和包衣增重为影响释放的重要因素,采用星点设计-效应面法得到扎西他宾微孔渗透泵控释片最优处方。在微孔渗透泵控释片最优处方的基础上,筛选出单室渗透泵控释片最优处方。分别按最优处方制备3批渗透泵控释片,并以累积释放度与时间进行零级方程拟合考察其释药特性。结果 扎西他宾微孔渗透泵控释片处方优化结果为:促渗透活性物质乳糖的量(X1)为每片80 mg、致孔剂PEG400的量为(X2)9%、包衣增重(X3)为2.8%;单室渗透泵最优处方为:乳糖每片15 mg,包衣增重2.5%,激光单面打孔,打孔脉冲为20 ms。结论 制备的2种扎西他宾渗透泵控释片工艺简单,质量可控。扎西他宾单室渗透泵片相对于微孔渗透泵片控释时间可延长至24 h,具有零级释药特征。
Abstract
OBJECTIVE To prepare micro-porous osmotic pump(MPOP) and elementary osmotic pump(EOP) controlled-release tablets of zalcitabine. METHODS A method to determine the drug release of the tablets was developed. Single-factor experiments revealed that quantities of osmogents and pore forming agents, as well as weight gains of coatings play important impacts on drug release. Central composite design was used to find the optimal formula of zalcitabine MPOP tablet, from which the optimal formula of EOP was screened. Zalcitabine MPOP and EOP tablets(3 batches each) were prepared according to the optimal formula and assessed by the zero-order equation fitting between cumulative release and time for their releasing characterizations. RESULTS The optimal formula of zalcitabine MPOP tablets are: quantities of lactose as the osmogent(X1) is 80 mg per tablet, PEG400 as the pore forming agent(X2) is 9%, the weight gain of coating(X3) is 2.8%. The optimal formula of EOP tablets are: quantities of lactose is 15 mg per tablet, the weight gain of coating is 2.5%, tablets were drilled on one side at a laser pulse of 20 microsecond. CONCLUSION The two osmotic pump tablets are prepared by simple processes with controllable quality and good stability. Controlled releasing duration of EOP could be extended to 24hrs compared with that of CPOP with a zero-equation release characterization.
关键词
微孔渗透泵 /
单室渗透泵 /
控释片 /
扎西他宾
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Key words
micro-porous osmotic pump(MPOP) /
elementary osmotic pump(EOP) /
controlled-release tablet /
zalcitabine
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中图分类号：
R944
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参考文献
[1] SHEN P, CHENG Q H, JIANG L P, et al. Characteristic analysis of HIV/AIDS deaths in Qinnan District of Qinzhou, 2010-2014[J]. China Trop Med(中国热带医学), 2018, 18(1): 89-92
[2] YANG H, QING M, GAO W E. Synthesis and characterization of Zalcitabine prodrugs[J]. J Tianjin Norm Univ Nat Sci Ed(天津师范大学学报 自然科学版), 2010, 30(2): 52-54.
[3] LIU X R.Treatment Drug of AIDS zalcitabine[J].World Clin Drug(世界临床药物),1994,(1):50-51.
[4] YU J J, MENG X, DONG X, et al. Synthesis and characterization of osmotic pump capsules containing polyoxyethylene and pH modifier to control the release of nifedipine[J]. Eur J Pharm Biopharm,2021,163:102-108.
[5] LI M, SHEN Q, LU W J, et al. Development and evaluation of controlled release of metformin hydrochloride for improving the oral bioavailability based on a novel enteric osmotic pump capsule[J]. J Drug Deliv Sci Technol,2020,60:102054.
[6] LI Y N, PAN H, DUAN H L, et al. Double-layered osmotic pump controlled release tablets of actarit: In vitro and in vivo evaluation[J]. Asian J Pharm Sci,2019,14(3):340-348.
[7] SUN Y L, ZHU S S, LU W J, et al. A novel enteric positioning osmotic pump capsule-based controlled release system of sinomenine hydrochloride: in vitro and in vivo evaluation[J]. J Drug Deliv Sci Technol,2019,49:188-194.
[8] GONG W, MA R, MEI D, et al. A novel subcutaneous infusion delivery system based on osmotic pump: in vitro and in vivo evaluation[J]. Drug Deliv, 2014, 21(1):1-7.
[9] CHINMAYA K S, NALINI K S, MUVVALA S, et al. A review on controlled porosity osmotic pump tablets and its evaluation[J]. Bull Facul Pharm,2015,53(2):195-205.
[10] JIN D, WANG B, HU R, et al. A novel colon-specific osmotic pump capsule of panax notoginseng saponins(PNS): Formulation, optimization, and in vitro-in vivo evaluation[J]. AAPS PharmSciTech, 2018, 19(5):2322-2329.
[11] ZHANG S, SUN Y H, ZHOU L, et al. Osmotic pump tablets with solid dispersions synergized by hydrophilic polymers and mesoporous silica improve in vitro/in vivo performance of cilostazol[J]. Int J Pharm, 2020, 588:119759.
[12] HABIB B A, ABDELREHIM R T, NOUR S A. Feasibility of optimizing trimetazidine dihydrochloride release from controlled porosity osmotic pump tablets of directly compressed cores[J].J Adv Res,2014,5(3):347-356.
[13] LIU X, WANG S, CHAI L, et al. A two-step strategy to design high bioavailable controlled-release nimodipine tablets: the push-pull osmotic pump in combination with the micronization/solid dispersion techniques[J]. Int J Pharm, 2014,461: 529-539.
[14] PAN H, JING H, YANG X, et al. Synchronized and controlled release of metformin hydrochloride/glipizide from elementary osmotic delivery[J]. Drug Dev Ind Pharm, 2017,43: 780-788.
[15] USP43-NF38[S]. 2020:5056-5057.
[16] ZHANG Y,WANG Y C,TANG K H,et al. Dissolution determ inat ion of Zalcitab ine from film-coated tab lets by HPLC[J]. West China J Pharm Sci(华西药学杂志), 2007, (4):433-435.
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脚注
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基金
抗生素研究与再评价四川省重点实验室开放课题资助(ARRLKF14-03)
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