Sustained Release of Amoxicillin from Chitosan Tablets

Sustained release systems in the forms of chitosan (CTS) tablet and extrude for releasing amoxicillin were studied. The degradation of amoxicillin in pH 1.2 was determined. The effects of particle sizes of chitosan on the dissolution profiles were investigated. The result showed that chitosan with the particle size less than 75 microm yielded the best controlled release pattern and it was comparable to that was obtained from the hydroxypropylmethylcellulose (HPMC) tablets. Moreover, the tablets containing chitosan with particle size less than 75 microm were able to provide a significantly improved sustained release profile of amoxicillin compared to the release profile of a commercial capsule. All release profiles of amoxicillin from the chitosan tablets could be described by first-order kinetics.     

格列齐特缓释片的研制及体外释放度考察

目的;制备格列齐特缓释片并考察其体外释放度。方法采用混合骨架材料制备格列齐特缓释片;参照进口格列齐特缓释片标准,采用紫外分光光度法,以pH7.4磷酸盐缓冲液900ml为溶剂,桨法测定本品释放度,并与参比制剂进行比较。结果所得缓释片体外释放度符合一级动力学规律,释放曲线经相似因子(f2)判断,与参比制剂相似。结论本品处方工艺稳定、重现性好,体外累积释放度符合要求。     

萘普生钠缓释片剂的研究

目的：研制萘普生钠缓释片剂。方法：采用硬脂酸包裹和水凝胶缓释技术及ＵＶ测定法,研究了奈普生钠骨架型缓释片剂。结果：缓释片释放试验结果表明本品缓释效果明显,１２ｈ内药物释放曲线符合Ｈｉｇｕｃｈｉ方程（Ｑ＝３１．４６＾１／２－７．９１ ＝０．９９４ ７）。结论：本方法较适合于大剂量、易溶性药物缓释制剂的制备。     

辛伐他汀-烟酸双层缓释片的制备及其体外质量评价

目的 制备辛伐他汀(SVT) -烟酸(NA)双层缓释片并进行体外质量评价.方法 分别通过正交实验和单因素实验,筛选NA缓释层与SVT常释层处方,确定最佳处方组成并制备SVT-NA双层缓释片,测定缓释片中NA与SVT的含量.以国内已上市NA缓释片为参比制剂,测定自制双层缓释片中NA的释放度,计算释放度相似因子(f2),并进行方程拟合.按照中国药典2010版中SVT普通片溶出度测定条件,测定自制双层缓释片常释层中SVT的溶出度.结果 自制双层缓释片中NA的释放度与市售NA缓释片相似(f2＞75),其释放行为符合Higuchi方程;常释层中SVT 30 min内的累积溶出度＞98％,符合中国药典有关规定.结论 SVT-NA双层缓释片处方组成合理,制备工艺稳定,重现性良好,有望开发成为新的复方制剂.     

尼莫地平由溶胀性亲水性骨架中释放的动力学

本研究选用尼莫地平PVP－K30固体分散体为原料,以羟丙基甲基纤维素（HPMC）为缓释材料,进行了尼莫地平缓释片剂处方的设计,考查其体外释药动力学,并对几种辅及及不同的制备方法对片剂释药情况的影响进行了研究。体外溶出度实验结果表明,在本实验范围内,尼莫地平由HPMC亲水性凝胶骨架片中的溶出过程更符合零级动力学。微晶纤维素的加入可使片剂释药速度加快,低粘度的羟乙基纤维素可使药物的溶出速率常数增加。将HPMC制成40目颗粒后,再行压片,可使药物溶出度减慢。本研究筛选出的缓释片剂,可在12小时内平稳释药。     

盐酸溴己新缓释片的制备及体外释放度研究

目的制备盐酸溴已新（Bromhexine hydrochloride．BH）缓释片。方法以聚乙烯毗咯烷酮（PVP）为载体。将盐酸溴己新制成固体分散体．再以羟丙甲基纤维素（HPMC）为骨架材料,采用湿法制粒压片制备盐酸溴己新缓释片,并进行体外释放度试验。结果所制备的缓释片12h内呈现良好的缓释特性,符合Higuchi方程。结论盐酸澳己新缓释片体外释药缓慢、平稳,符合设计要求。     

氢溴酸加兰他敏缓释片的研制

目的研制氢溴酸加兰他敏缓释片并建立释放度测定方法。方法用正交设计优选处方,以单硬脂酸甘油酯、Eudragit L100-55为主要缓释材料,考察其用量及滑石粉用量对缓释片的影响。用紫外-可见分光光度法测定主药含量,并根据《中国药典》2005年版释放度测定方法,建立了体外释放度测定方法。结果氢溴酸加兰他敏缓释片在24 h内呈现良好的缓释特征,释药行为符合Higuchi方程,制备工艺及释放度测定方法简单易行。结论该氢溴酸加兰他敏缓释片处方设计合理,可进一步研究开发。     

Influence of enteric-coated lactose on the release profile of 4-aminopyridine from HPMC matrix tablets

A weakly basic experimental drug, 4-aminopyridine, was taken as a model to study the influence of enteric-coated lactose (EL) on the release profile from hydroxypropyl methylcellulose matrices. Powder mixtures were wet-granulated with water. The dried granulation was compressed with a hydraulic press at 85 MPa. Dissolution studies were made using HCl 0.1 N and then phosphate buffer pH 7.4. Dissolution curves were described by M(t)/M(inf) = k*t(N). A trend toward increasing exponent (n) and decreasing release constant (k) values is observed with increasing EL concentrations up to 9%; this is attributed to an increasing obstruction of the diffusion path by isolated EL particles that are insoluble in HCl and are surrounded by a water-filled space. After a critical EL concentration, the water-filled spaces surrounding EL particles percolate, producing the opposite effect, increasing the release constant and decreasing the exponent (n) values as the EL proportion increases from 10% to 50%. EL particles (2% to 9%) decrease the drug and water transport in matrices dissolving in HCl. Thereafter, at pH 7.4, the pores formed by dissolution of EL particles produce the opposite. Both processes contribute to flattening the release profile. Release profiles with decreasing release constant values show a logarithmic trend toward increasing values of the exponent (n), changing from diffusion toward relaxation-erosion-controlled processes.     

盐酸伐昔洛韦缓释片体外释放与体内吸收的相关性

以转篮法测定盐酸伐昔洛韦缓释片的体外释放度并进行体内试验。单剂量交叉给予家犬相同剂量的盐酸伐昔洛韦缓释片和普通片后测定血药浓度，分别以Wagner—Nelson法和反卷积分法计算体内吸收分数与输入函数，进行体内外相关性的判断。结果表明盐酸伐昔洛韦缓释片体内外相关性良好。     

Preparation and biopharmaceutical evaluation of microcapsules of amoxicillin

Two methods of microencapsulation of amoxicillin, an orally administered antibiotic, were studied. One is based on dispersion of gelatin-amoxicillin mixture in liquid paraffin followed by drying and hardening with formalin-isopropanol treatment; the other is based on dispersion of ethylcellulose-amoxicillin mixture in purified water containing sodium lauryl benzene sulphonate. The microcapsules were recovered as discrete, free-flowing fine granules with a particle diameter of about 250-1000 microns. Dissolution of amoxicillin from ethylcellulose microcapsules was suppressed considerably with a zero-order dissolution pattern in solutions of various pH. Gastric-emptying-controlled rabbits were used for the in vivo evaluation of gelatin and ethylcellulose microcapsules. The ethylcellulose microcapsule containing 25 per cent amoxicillin showed a significantly sustained release pattern of amoxicillin. To establish a suitable design and for the evaluation of the sustained release microcapsules, a nomogram was made using pharmacokinetic parameters obtained after administration of a conventional formulation. It is advantageous for the preparation of sustained release microcapsules to chose pharmaceuticals having over about 2 as the ratio of the elimination rate constant, k10, to the release/absorption rate constant, kr, in the rabbit.     

四乙酰基葛根素双层缓释片的制备及体外释放研究

目的研制四乙酰基葛根素双层片并考察其体外释药特征。方法干法制粒压制双层片,HPLC测定四乙酰基葛根素的释放度。结果考察得到四乙酰基葛根素双层缓释片处方合理,其释药曲线用Higuchi方程拟合,可维持12h持续释放。结论四乙酰基葛根素双层缓释片的研制达到设计要求。     

复方氨茶碱缓释片的制备

目的:制备复方氨茶碱缓释片。方法:用正交试验优化处方,以羟丙甲基纤维素为骨架材料,用疏水性阻滞剂乙基纤维素调节药物释放速度,采用湿法制粒压片制备复方氨茶碱缓释片。用紫外分光光度法测定主药氨茶碱的含量,用HPLC法测定其他组分的含量。通过测定氨茶碱的体外释放度,进行释放机制及影响因素的研究。结果:所制备的缓释片12h内呈现良好的缓释特性,符合Higuchi方程:Q=24.176 0t1/2-7.699,r=0.995 6。结论:复方氨茶碱缓释片体外释药缓慢、平稳,符合设计要求。     

曲尼司特缓释片的制备及其释药影响因素研究

目的　制备了曲尼司特凝胶骨架片。方法　采用HPMCK4M、K15M为凝胶骨架材料 ,进行了处方研究 ;通过测定制剂体外释放度 ,评价了该缓释片处方。结果　曲尼司特缓释片体外释药符合Higuchi方程 ,其释药速率常数Kr为 0 193h-1/ 2 。影响缓释片体外释药的因素有骨架材料的种类、用量、粘合剂的种类和释药介质的pH等。结论　缓释片具有明显的缓释作用 ,可缓慢释药 12h。     

硝苯地平缓释片与普通片在健康人体内药动学的比较

目的比较硝苯地平缓释片与硝苯地平普通片在健康人体内药动学。方法 12名男性健康志愿者平均分为2组,分别单剂量口服硝苯地平缓释片与硝苯地平普通片20 mg,用高效液相色谱法检测硝苯地平的血药浓度,并用DAS 2.1软件进行数据处理。结果硝苯地平缓释片与硝苯地平普通片主要药动学参数ρmax分别为(1 247.8±78.4)μg.L-1和(1 896.7±109.2)μg.L-1,tmax分别为(4.6±0.7)h和(2.6±0.9)h,t1/2分别为(8.6±2.8)h和(4.8±1.5)h,AUC0-∞分别为(5 879.3±176.2)μg.h.L-1和(3 724.9±121.3)μg.h.L-1,AUC0-t分别为(4 427.8±131.7)μg.h.L-1和(2 936.5±75.4)μg.h.L-1。结论硝苯地平缓释片的tmax、t1/2长于普通片,AUC0-t、AUC0-∞高于普通片,而ρmax低于普通片,说明硝苯地平缓释片具有良好的缓释效果。     

不同厂家生产的盐酸曲马多缓释片整片与半片的三维释放特性考察

目的:对不同厂家(A、B、C)的盐酸曲马多缓释片的整片与半片进行pH-时间-释放度考察,探讨整片与半片体外释放机制的差异.方法:转篮法,用紫外分光光度法检测,描绘其三维释放图像,将释放数据用相似因子法、Peppas方程进行分析.结果:在同一pH条件下,A、C的整片与半片释放曲线不相似,释放机制也不相同;B的整片与半片释放曲线相似,释放机制相同.结论:不同厂家盐酸曲马多缓释片整片与半片的体外释放不尽相同.     

吲哚美辛缓释胶囊与普通胶囊的生物利用度比较

本文比较了吲哚美辛(消炎痛)缓释胶囊和一种普通胶囊在体外的溶出速率以及在人体内生物利用度。吲哚美辛血清浓度用高效液相色谱(HPLC)测定。结果表明,2种胶囊制剂的溶出速率显著不同。在8名受试者中,2种胶囊的吸收程度基本一致;但缓释胶囊的峰药浓度(C_(max))显著低于普通胶囊(P<0.01),其达峰时间(T_(max))也明显延迟(P<0.01)。给予单剂量(50mg)缓释胶囊后,在给药后h4至h12,其血清浓度显著高于普通胶囊(P<0.05)。提示该缓释剂可避免普通制剂初期的高峰药浓度,可延长给药间隔时间。     

单剂量口服法莫替丁缓释片的药代动力学

选择６名男性健康志愿者，通过ＨＰＬＣ法测定单剂量口服法莫替丁缓释片和普通市售片后的血药浓度，用３ｐ８７程序处理数据，研究该药缓释制剂的药代动力学和生物利用度，并考察了体内吸收率与体外溶出度的相关性．结果表明，两种剂型在体内血药浓度－时间曲线均符合一室模型．法莫替丁缓释片的主要药代动力学参数为：Ｔｍａｘ＝４．６ｈ，Ｃｍａｘ＝５０．９６μｇ／Ｌ，Ｔ１／２ｋｅ＝５．０４ｈ，ＡＵＣ＝６９６．８６μｇ·ｈ／Ｌ．其相对生物利用度为１１６％．     

美乐托宁缓释片在不同介质中的释放试验

目的:制备美乐托宁缓释片,以国外上市制剂美乐托宁缓释片为参比制剂,考察自研制剂和参比制剂在不同pH释放介质中体外释放行为的相似性及体外释药机制。方法:采用释放度测定法转篮法的装置进行体外释放实验,用HPLC法测定释放度,采用f2相似因子对2种制剂释放曲线的相似度进行评价,并进行释放行为模型的拟合。结果:在不同pH的释放介质中,自制制剂释放度曲线与参比制剂比较,f2相似因子均大于50;美乐托宁缓释片在4种释放介质中体外释药拟合模型更接近一级方程、Higuchi方程和Peppas方程。结论:参比制剂与自制制剂在不同pH释放介质中的体外释放一致,释放机制为扩散释药。     

盐酸加巴喷丁缓释片的研制

目的:研制盐酸加巴喷丁缓释片。方法:利用单因素优化设计法优化处方制备工艺,建立HPLC法测定释放度。结果:最佳处方为盐酸加巴喷丁180 mg,K15M型HPMC 150 mg,CMC·Na 50 mg,可压性淀粉20 mg,5%PVP(K25)95%的乙醇溶液适量,0.5%硬脂酸镁作润滑剂。结论:该优选条件制备的加巴喷丁缓释片工艺简单,体外释药具有明显的12 h缓释作用。     

洛索洛芬钠双层缓释片的研制和体外释放特性研究

目的：研制洛索洛芬钠双层缓释片并考察其体外释药特性。方法：以两种不同处方作湿法制粒,压制双层片,用高效液相色谱法测定洛索洛芬钠的释放度.结果与结论：洛索洛芬钠双层缓释片的释药曲线可用Higuchi方程或Peppas方程拟合,可维持12h持续释放达到设计要求.