In vitro characterization and release study of Ambroxol hydrochloride matrix tablets prepared by direct compression

A series of either hydrophilic or hydrophobic polymers were used to prepare controlled release Ambroxol hydrochloride (AMX) matrix tablets by direct compression. Both the compatibility and flow properties of AMX/polymer mixtures were investigated. The effect of the amount and type of polymer on the physical properties and in vitro drug release was studied and compared to commercially available Ambroxol^® SR capsules. A kinetic study of the release profile of AMX from the prepared matrix tablets was performed. All excipients used in the study were compatible with the model drug. AMX/drug mixtures containing sodium alginate (NA) and hydroxypropylmethyl cellulose (HPMC) showed better flow properties than other polymers used in the study. The in vitro drug release studies showed that matrix tablets formulae containing 10% HPMC (S7) or a combination of 30% NA and 5% HPMC (Ah) exhibited a higher ability to control the release of AMX. The kinetic study revealed that a diffusion controlled mechanism prevailed except when carbopol was used. Formula Ah followed a non-fickian diffusion mechanism similar to Ambroxol^® SR capsules. Both formulae S7 and Ah could be considered as potential candidates for formulation of AMX controlled release matrix tablets.     

In vitro characterization and release study of Ambroxol hydrochloride matrix tablets prepared by direct compression

A series of either hydrophilic or hydrophobic polymers were used to prepare controlled release Ambroxol hydrochloride (AMX) matrix tablets by direct compression. Both the compatibility and flow properties of AMX/polymer mixtures were investigated. The effect of the amount and type of polymer on the physical properties and in vitro drug release was studied and compared to commercially available Ambroxol(?) SR capsules. A kinetic study of the release profile of AMX from the prepared matrix tablets was performed. All excipients used in the study were compatible with the model drug. AMX/drug mixtures containing sodium alginate (NA) and hydroxypropylmethyl cellulose (HPMC) showed better flow properties than other polymers used in the study. The in vitro drug release studies showed that matrix tablets formulae containing 10% HPMC (S7) or a combination of 30% NA and 5% HPMC (Ah) exhibited a higher ability to control the release of AMX. The kinetic study revealed that a diffusion controlled mechanism prevailed except when carbopol was used. Formula Ah followed a non-fickian diffusion mechanism similar to Ambroxol(?) SR capsules. Both formulae S7 and Ah could be considered as potential candidates for formulation of AMX controlled release matrix tablets.     

In vitro controlled release of sodium ferulate from Compritol 888 ATO-based matrix tablets

A controlled release matrix formulation for freely water-soluble drug of sodium ferulate (SF) was designed and developed to achieve a 24h release profile. Using Compritol 888 ATO as an inert matrix-forming agent to control the release of SF, formulation granules containing the physical mixtures or solid dispersions were investigated. The matrix tablets for these formulations were prepared by direct compression and their in vitro release tests were carried out. The solid dispersion based tablets were found to be more effective than those compressed from physical mixtures in retarding the release of SF. Drug release from the matrix tablets containing physical mixtures nearly completed within 12h, while that from the solid dispersion formulations lasted for over 24h. Images of the tablet surface and cross-section were characterized by scanning electron microscopy to show the formed pores and channels in the matrices. These might provide the release pathway for the inner embedded drugs. Drug released fast from the matrix tablets with the release-enhancer of lactose. The addition of surfactants was also found to increase the release rate of SF effectively. Moreover, the co-mixing of polyethylene glycol 6000 (PEG 6000) in the waxy matrices played a meaningful role in controlling the drug release for 24h. The drug release from the novel formulation might be attributed to the diffusion-controlled mechanism.     

Effect of formulation variables on drug and polymer release from HPMC-based matrix tablets

The objective of this work was to assess the effect of two formulation variables, hydroxypropylmethylcellulose (HPMC)/lactose ratio and HPMC viscosity grade, on the release of a model drug and HPMC, as well as the mechanism of drug release from HPMC-based matrix tablets. A water-soluble compound, adinazolam mesylate, was used as the model drug. Both drug and HPMC release were found to be a function of the formulation variables, with higher drug and HPMC release rates for formulations with lower HPMC/lactose ratios and lower HPMC viscosity grades. However, the K15M and K100M formulations had identical drug release profiles. All the drug release data fit well to the Higuchi expression. By comparing the drug and HPMC release data, it was concluded that diffusion of drug through the hydrated gel layer was the predominant drug release mechanism for most of the formulations studied.     

盐酸二甲双胍渗透泵控释片的制备及体外释放度考察

目的研究盐酸二甲双胍渗透泵控释片的制备工艺及体外释药的影响因素。方法通过单因素考察和正交试验,优化制备工艺。结果盐酸二甲双胍渗透泵控释片的体外释药符合零级释放规律,释药速率受PEG种类、PEG用量、包衣膜重量影响较大,在一定范围内,释药孔大小、片芯硬度、溶出介质pH值和桨转速对其影响较小。结论盐酸二甲双胍渗透泵控释片工艺稳定,能够达到9h明显的恒速释药。     

己酮可可碱控释片的制备及体外释放度的考察

目的：研究己酮可可碱控释片的处方工艺。方法：对片芯组成进行考察，采用薄膜包衣技术制备己酮可可碱控释片。利用相似因子对优化处方重现性进行评价。结果：致孔剂用量、渗透促进剂种类和崩解剂用量对释药曲线有明显的影响，自制片符合零级释药特征。结论：该控释片处方及制备工艺简单，重现性好，适合工业生产，同时为水溶性大剂量药物制备成控释片提供了一种新的方法。     

影响石杉碱甲骨架片体外释放因素的研究

目的自制石杉碱甲骨架缓释片（HA-MT），考察石杉碱甲骨架片中释放的体外释放特性。方法考察通过释放度实验研究不同制片工艺、测定方法、释放介质的pH值、搅拌转速对骨架片释药的影响，并考察其释药机制。结果制片方法、测定方法对释药行为影响不明显，但转速和溶出介质有明显影响。药物释放曲线符合HIGUCHI方程。结论制备的HA-MT工艺简易，释药达到缓控释要求，释药机制为扩散和溶蚀机制协同作用。     

复方盐酸伪麻黄碱镶嵌缓释片的制备及其体外释放度的测定

目的　制备盐酸伪麻黄碱和萘普生钠复方镶嵌缓释片,并研究其体外释放特性。方法　以亲水凝胶(ＨＰＭＣＫ100Ｍ)为缓释部分基质,采用二次压片的工艺研制了盐酸伪麻黄碱和萘普生钠复方镶嵌缓释片;以磷酸盐缓冲液(ｐＨ7.2)为释放介质,采用紫外分光光度法和酸性染料比色法分别测定了释放液中萘普生钠和盐酸伪麻黄碱的含量,并计算其体外释放度。结果　自制盐酸伪麻黄碱和萘普生钠复方镶嵌缓释片中萘普生钠在0 .5ｈ的释放量大于75%,盐酸伪麻黄碱在0 5ｈ的累积释放约7%±3. 6%,1ｈ为15. 8%±2 .3%,4ｈ为49 .5%±3 .9%,8ｈ在85%以上。结论　该复方镶嵌缓释片兼具速释和缓释特点,效果显著。     

盐酸氨溴索渗透泵控释片的研制

目的：制备盐酸氨澳索口服渗透泵控释片。方法：使用羟丙基-β-环糊精对盐酸氨澳索包合，应用正交设计优化渗透泵片处方。结果：制得的盐酸氨澳索渗透泵控释片释放度符合要求。结论：羟丙基-β-环糊精能够改善盐酸氨澳索的溶解性质，从而简化盐酸氨澳索渗透泵制剂的制备方法。     

盐酸二甲双胍渗透泵制剂的制备和释药因素的研究

目的 探索一种盐酸二甲双胍微孔型渗透泵控释片的制备方法并研究其释药行为的影响因素.方法 以聚醋酸乙烯酯水分散体为控释材料制备盐酸二甲双胍渗透泵控释片,考察增塑剂、致孔剂、溶出介质等因素对药物溶出的影响.结果 以聚醋酸乙烯酯水分散体包衣制得盐酸二甲双胍渗透泵控释片的可实现稳定的零级释放.结论 聚醋酸乙烯酯可用于制备微孔型渗透泵制剂,该制备方案有望为渗透泵制剂的研究提供一种新的选择.     

TJ0711盐酸盐缓释片的制备及体外释放特性考察

目的:研制TJ0711盐酸盐混合骨架缓释片,并评价其体外释放特性。方法:研究了HPMC的黏度和用量,十八醇、CMC-Na的用量对药物释放的影响,并通过正交试验设计对片剂的处方进行优化。结果:正交设计所得最优处方为十八醇、HPMC K4M、CMC-Na的用量分别为片重的20%,40%,10%。药物体外释放良好,符合Higuchi模型(Q=33.909t1/2-20.263,r=0.996 2),持续释药达12 h。结论:经正交优化的TJ0711盐酸盐缓释片处方可行。     

Optimization of pH-independent release of nicardipine hydrochloride extended-release matrix tablets using response surface methodology

The purpose of this study was to optimize the pH-dependent release of nicardipine hydrochloride extended release formulations by using simultaneously combination two hydrophilic polymers: hydroxypropylmethylcellulose (HPMC) and sodium alginate as retardant and avicel as additive. The constrained mixture experimental design was used to prepare systematic model formulations which were composed of three formulation variables: the content of HPMC (X1), avicel (X2), and sodium alginate (X3). The response surface methodology (RSM) and multiple response optimization utilizing the polynomial equation were used to search for the optimal formulation with specific release rate at different time intervals and to quantify the effect of each formulation variables. The drug release percent at 3, 6 and 12 h were the target responses and were restricted to 10-30% (Y3h), 40-65% (Y6h) and not less than 80% (Y12h), respectively. The results showed that the effect of combination of HPMC and sodium alginate was the most influence factor on the drug release from extended-release matrix tablets. The observed results of Y3h, Y6h and Y12h coincided well with the predictions in the RSM optimization technique, indicating it was quite useful for optimizing pharmaceutical formulation. The mechanism of drug release from extended-release matrix tablets was dependent on the added amount of alginate. The release kinetic of drug from HPMC matrix tablets with alginate was followed the zero-order release pattern.     

A comparative study of controlled release matrix tablets of diclofenac sodium, ciprofloxacin hydrochloride, and theophylline

The need for controlled release formulations for diclofenac sodium, ciprofloxacin, and theophylline is well recognized. In our study, controlled release tablets of the three drugs were formulated by the matrix-embedding technique using ethyl cellulose as retardant. Tablets of all the drugs were of good physical quality with respect to appearance, drug content uniformity, hardness, weight variation, and friability. In vitro release rate studies showed that ethyl cellulose extended the release of the three drugs to 12 hr or more. Release patterns from formulations of the three drugs followed Higuchi's square root kinetics. At pH 6.8, the release rate was higher in all three drugs, probably due to increased solubility of the drugs and/or increased swelling of ethyl cellulose at the higher pH. The formulations were highly stable and possessed reproducible release kinetics across batches.     

Preparation and comparative evaluation of sustained release metoclopramide hydrochloride matrix tablets

Metoclopramide hydrochloride (MCP) is commonly used for the management of gastrointestinal disorders. Frequent administration and the undesired side effects (extra pyramidal symptoms) of the drug on the central nervous system due to the fluctuations of its plasma concentrations may lead to patient incompliance, and hence, improper therapy. Therefore, the present work will be devoted to formulate the drug in sustained release formulations. MCP was incorporated in 12 formulae containing different polymers and/or different polymer ratios. These polymers were hydroxypropylmethyl cellulose (HPMC), carboxymethylcellulose (CMC) and ethyl cellulose (EC). Sodium starch glycolate (SSG) was added to some formulae in different amounts in order to soften and/or disintegrate the tablets. Both direct compression and granulation techniques were used to prepare the tablets. The physical properties were found to be satisfactory for all the formulae. The dissolution profiles of the tablets were constructed using the change-over method. The drug release involved a combination of both diffusion and polymer-chain relaxation mechanisms. The time required to release 50% of MCP ranged from 1.2 to more than 8 h. Direct compression and dry granulation techniques produced sufficient sustaining of the drug release. However, the pellets made by wet granulation released MCP in about 2 h, i.e., pelletization spheronization technique was not effective in sustaining the drug.     

西替伪麻缓释片释放度测定方法研究

目的探讨西替伪麻缓释片的体外释放特性.方法以水为溶剂,采用<中国药典>2000年版二部溶出度测定第一法测定装置测定,定量测定采用高效液相法测定.对均一性、释放度曲线、不同溶剂介质的释放特点进行了考察.结果盐酸伪麻黄碱的释药曲线可用一级方程动力学拟合,证明国产西替伪麻缓释片具有较好的体外释放特性.结论该方法简便、宜行.     

不同厂家盐酸伐昔洛韦片的体外溶出曲线比较

目的比较3个厂家盐酸伐昔洛韦片在4种溶出介质中溶出曲线的相似性。方法采用《中国药典》2010年版溶出度测定方法第一法装置,转速为50r/min,分别以pH1.2盐酸溶液、pH4.5醋酸盐缓冲液、pH6.8磷酸盐缓冲液和水为溶出介质,在252nm波长处测定吸光度,绘制3个厂家盐酸伐昔洛韦片的体外溶出曲线,并采用f2相似因子法考察其相似性。结果在4种不同溶出介质中,3个厂家的盐酸伐昔洛韦片溶出曲线的f2值差异较大,有1厂家产品只在一种介质中的溶出曲线与参比制剂相似,而另1厂家产品只在一种介质中的溶出曲线与参比制剂不相似。结论不同厂家的辅料、生产工艺和生产规模导致了盐酸伐昔洛韦片溶出度的差异。     

秋水仙碱双层片体外释放研究

目的建立秋水仙碱双层片体外释放方法,并考察工艺、体外释放条件与缓速释比例对秋水仙碱双层片释药的影响。方法采用相似因子（f2）法评价释药曲线的相似性,并分别用零级、一级、Higuchi、Peppas方程拟合优化处方。结果工艺对秋水仙碱双层片影响较小,浆速对秋水仙碱双层片影响较大。依据最优处方制备的控释片在1～12h呈良好的缓释释放特征,12h累积释药率90％以上。结论建立了较为准确、可靠的秋水仙碱双层片体外释放度测定方法,体外释放度结果符合要求。     

格列齐特生物溶蚀性骨架片的制备及体外释放度研究

目的建立格列齐特缓释片的释放度测定方法。方法采用转蓝法,以pH 7.4磷酸盐缓冲液为溶出介质,转速为100 r.m in-1,照分光光度法检测,测定波长226 nm。结果格列齐特2.04~20.40 mg.L-1范围内吸收度与浓度呈良好的线性关系,r=0.999 9,平均回收率为100.9%,RSD=1.07%(n=12),与国外上市的同规格产品D iam icronMR一致。结论方法操作简便,准确可靠,可用于格列齐特缓释片的质量控制。