格列喹酮缓释片的研制及其体外释放度考察

目的研制格列喹酮缓释片并考察其释药机制。方法以HPMC为骨架材料,以乳糖、淀粉、微晶纤维素作为填充剂调节释放度,并采用正交试验筛选处方,采用数学模型拟合释放曲线。结果格列喹酮缓释片在24h内呈现良好的释药特征,释药行为符合0级方程,Peppas方程拟合曲线说明药物释放是骨架溶蚀作用的结果。结论格列喹酮缓释片体外释放试验显示缓释行为,可进一步研究开发。     

氢溴酸高乌甲素亲水凝胶骨架片的制备及体外释放

目的为了减少给药次数,方便患者,并提高镇痛效果,制备氢溴酸高乌甲素亲水凝胶骨架片,优化制剂处方,并探讨释放机制。方法以羟丙甲纤维素(HPMC)为骨架材料,乳糖、微晶纤维素(MCC)、淀粉为填充剂,硬脂酸镁为润滑剂制备氢溴酸高乌甲素骨架片,考察各因素对药物释放度的影响,筛选优化处方,并拟合讨论其释放机制。结果 HPMC的用量及分子量,微晶纤维素和硬脂酸镁的用量对药物释放有显著影响。所制缓释片无突释现象,缓释周期12 h,根据拟合方程,药物释放符合一级释放模型,其释放既有扩散,又有骨架溶蚀。结论本方法制备的氢溴酸高乌甲素缓释片工艺简单,生产成本低,且具有良好的释放性能。     

吲达帕胺缓释片的研制及释药机理考察

目的：研制吲达帕胺缓释片，并考察其释药机理。方法：以HPMC为骨架材料，以微晶纤维素、乳糖和可压性淀粉调节释放度，对吲达帕胺缓释片的影响因素进行了考察，并采用正交试验设计筛选处方。结果：吲达帕胺缓释片的组成为：HPMC K4M 37．5mg，HPMC K15M7．5mg，乳糖45．0mg，可压性淀粉37．5mg，微晶纤维素21．0mg，硬脂酸镁1．5mg，药物的释放符合零级动力学方程，释放机制为骨架溶蚀机制；释药速率受介质pH值的影响，几乎不受压片压力的影响。结论：研制的吲达帕胺缓释片体外释放符合国外同类产品的释药特性。     

盐酸倍他司汀缓释骨架片的制备及体外释药特性研究

摘 要 目的： 制备盐酸倍他司汀缓释骨架片。方法: 采用亲水性高分子材料HPMC为骨架,制备盐酸倍他司汀缓释片,并用单因素试验考察其释药特征。正交试验优化处方工艺。结果:以60% HPMC K15M为骨架材料,磷酸氢钙为填充剂,用10%PVP的90%乙醇溶液为黏合剂,湿法制粒压片为最佳工艺,片重为500 mg。药物体外释放接近Higuchi模型,能实现药物12 h内缓慢释放。结论: 本品制备工艺简便,具有缓解特性。     

酒石酸美托洛尔缓释片工艺研究

目的对酒石酸美托洛尔缓释片的处方工艺进行研究。方法运用正交设计法,通过测定不同时间酒石酸美托洛尔的释放率,来判断其缓释效果从而对缓释骨架材料、填充剂、粘合剂、润滑剂的种类、规格、用量及工艺等进行考察,并对确定的处方及工艺制备的3批样品测定其释放度。结果用HPMC作为骨架材料,微晶纤维素作为填充剂,硬脂酸镁作为润滑剂,3%EC乙醇溶液作为粘合剂制成酒石酸美托洛尔缓释片。结论本制剂工艺简单,所用各种辅料均为国产化,成本低.制得酒石酸美托洛尔缓释片释放度符合规定。     

盐酸二甲双胍缓释片处方筛选及工艺研究

对盐酸二甲双胍缓释片的处方及工艺进行筛选和研究。方法：根据释放度作为判断原则，对缓释骨架材料、填充剂、粘合剂、润滑剂及包衣材料的种类、规格、用量及工艺等进行了考察，并在此基础上采用正交试验1．9(3^4)方案对处方进行筛选。结果：以HPMC K100M及HPMC K15M作为盐酸二甲双胍缓释片的基本骨架材料，微晶纤维素作为填充剂，硬脂酸镁为润滑剂，4％HPMCE5的70％乙醇溶液适量作为粘合剂制成片芯，采用薄膜包衣法，以欧巴代的70％乙醇溶液作为薄膜包衣材料，制得盐酸二甲双胍缓释骨架片。结论：本制剂工艺简单，所用各种辅料均为国产化，成本低，制得盐酸二甲双胍缓释片释放度符合规定。     

盐酸曲美他嗪缓释片的研制及其体外释药特性考察

目的:研制盐酸曲美他嗪(TMZ)缓释片,并考察其体外药物释放特性。方法:以羟丙基甲基纤维素(HPMC)为主要骨架材料,采用湿法制粒压片法,制备TMZ缓释片;以释放度为评价指标,采用正交试验设计对处方进行优化;根据药物不同时间释放度,拟合释放度方程,确定释药特性。结果:TMZ缓释片的处方组成为:HPMC 90 mg,羧甲基纤维素钠30 mg,微晶纤维素60 mg,10%聚乙烯吡咯烷酮-乙醇溶液(w/v)适量,硬脂酸镁2 mg;12 h释放度为(98.1±1.8)%,体外释放曲线符合一级动力学方程(r=0.994 2);压片力对药物释放有一定影响。结论:研制的TMZ缓释片制备工艺简单,重现性好,释药特性达到缓释要求。     

马来酸氟吡汀缓释片的研制及体外释放特性考察

目的：采用羟丙甲基纤维素（HPMC）作为亲水凝胶骨架材料,制备马来酸氟吡汀缓释片,并考察其体外释放特性。方法：通过单因素试验,分剐考察了HPMC、乳糖用量对马来酸氟吡汀缓释片释放速率的影响;以体外释放度为评价指标优选处方的最佳组成和比例。结果：马来酸氟吡汀缓释片的释放速度随处方中HPMC含量增加而减慢,随乳糖用量增多而加快;释放介质对马来酸氟吡汀的释放速率也有明显影响,而释放度测定方法、转速对马来酸氟吡汀缓释片的释放速率无明显影响。结论：本品处方组成合理,制备工艺稳定。制备的马来酸氟吡汀缓释片,体外释药曲线显示有明显的缓释作用,属于零级释放。     

不同辅料对硝苯地平缓释片光稳定性影响研究

目的 考察硝苯地平缓释片中原料药与辅料的相容性,为更好地设计处方,控制和提高质量提供依据和信息。方法 采用中国药典2015年版二部硝苯地平原料药项下有关物质检查方法,考察有关物质变化,作为不同辅料对硝苯地平缓释片光稳定性的影响指标。结果 在光照条件下,硝苯地平易产生光降解杂质2,且微晶纤维素和硬脂酸镁会加速杂质2的产生。结论 在满足相关制剂要求的条件下,建议尽量少加或不加微晶纤维素和硬脂酸镁。     

西罗莫司缓释片的制备及其释药因素考察

目的制备西罗莫司缓释片并对其释药因素进行考察。方法采用羟丙基甲基纤维素（HPMC）为基本骨架材料制备了西罗莫司凝胶骨架片,对影响释药的因素,如采用羟丙基甲基纤维素（HPMC）规格、用量、填充剂种类、致孔剂用量、压片压力及释放介质等进行了考察。结果以30%羟丙基甲基纤维素（HPMC K4M）为骨架材料、2%乳糖为致孔剂、微晶纤维素（MCC）为填充剂时,缓释片呈明显一级释放特征。结论该制剂在体外具有良好的缓释效果,且制备工艺简单易行。     

Use of natural gums and cellulose derivatives in production of sustained release metoprolol tablets

Metoprolol tartrate sustained-release tablets (100 mg) were prepared using xanthan/guar gums and also hydroxypropyl methyl cellulose (HPMC) carboxymethyl-Cellulose (CMC) polymers by direct compression method. Physical characteristics of the tablets and water uptake in addition to their dissolution profiles were compared with standard (Lopressor® SR) tablets. Dissolution test was performed in the phosphate buffer solution (pH 6.8) and the samples were analyzed spectrophotometerically in 275.7 nm. Dissolution studies showed that formulations containing 100 and 80% of HPMC, 100% of guar, and 20% of xanthan followed the Higuchi model, while those containing 60 and 40% HPMC and 100 and 80% xanthan followed a zero-order model. The tablets with 40% xanthen followed a Hixon-Crowell model. In cellulose derivatives the highest MDT and dissolution efficiency until 8 hr (DE₈%) belonged to tablets with 40% HPMC, increasing the amount of CMC decreased the drug release rate, and formulations containing 60 and 40% of HPMC had the USP dissolution standards. While, in the gum formulations, the highest mean dissolution time and the lowest DE₈% belonged to tablets with 100% xanthan, increasing the xanthan decreased the release rate of metoprolol, and formulations containing 80 and 100% xanthan had the USP dissolution standards. Results showed that natural gums are suitable for production of sustained-release tablets of metoprolol.     

Development of Press-Coated,Floating-Pulsatile Drug Delivery of Lisinopril

Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor, primarily used for the treatment of hypertension, congestive heart failure, and heart attack. It belongs to BCS class III having a half-life of 12 hrs and 25% bioavailability. The purpose of the present work was to develop a press-coated, floating-pulsatile drug delivery system. The core tablet was formulated using the super-disintegrants crosprovidone and croscarmellose sodium. A press-coated tablet (barrier layer) contained the polymer carrageenan, xanthan gum, HPMC K4M, and HPMC K15M. The buoyant layer was optimized with HPMC K100M, sodium bicarbonate, and citric acid. The tablets were evaluated for physical characteristics, floating lag time, swelling index, FTIR, DSC, and in vitro and in vivo behavior. The 5% superdisintgrant showed good results. The FTIR and DSC study predicted no chemical interactions between the drug and excipients. The formulation containing xanthan gum showed drug retaining abilities, but failed to float. The tablet containing HPMC K15M showed a high swelling index. The lag time for the tablet coated with 200 mg carrageenan was 3±0.1 hrs with 99.99±1.5% drug release; with 140 mg HPMC K4M, the lag time was 3±0.1 hrs with 99.71±1.2% drug release; and with 120 mg HPMC K15M, the lag time was 3±0.2 hrs with 99.98±1.7% drug release. The release mechanism of the tablet followed the Korsmeyer-Peppas equation and a first-order release pattern. Floating and lag time behavior have shown good in vitro and in vivo correlations.     

星点设计-效应面法优化复方氯雷伪麻缓释片的缓释片芯处方

目的:优化复方氯雷伪麻缓释片的缓释片芯处方。方法:以氯雷他定加入包衣层并包衣硫酸伪麻黄碱片芯制备复方氯雷伪麻缓释片。采用星点设计-效应面法优化硫酸伪麻黄碱片芯处方,以单硬脂酸甘油酯(GM)和羟丙甲纤维素(HPMC)K15M用量为考察因素,以硫酸伪麻黄碱1、6、12 h的累积释放度为指标,通过重叠等高线图确定优化处方,并进行处方验证。结果:氯雷他定与欧巴代包衣粉按1∶3比例混合包衣成为速释层;硫酸伪麻黄碱片芯作为缓释层,其处方为每100片(600 mg/片)含硫酸伪麻黄碱12 g、GM 16.72 g、HPMC K15M 20.95 g、微晶纤维素9.73 g、硬脂酸镁0.6 g。优化处方所制制剂中氯雷他定15 min的累积溶出度为87.2%,硫酸伪麻黄碱1、6、12 h的累积释放度分别为34.20%、74.32%、94.60%。结论:缓释片芯处方合理、可行,所制备的复方氯雷伪麻缓释片具有缓释作用。     

Formulation and In vitro assessment of sustained release terbutaline sulfate tablet made from binary hydrophilic polymer mixtures

In the present systematic study, a sustained release of terbutaline sulfate tablet (TBS) was developed and optimized by employing the hydrophilic polymers; chitosan and xanthan gum mixed with sodium bicarbonate as a release modifying agent. This formulation was developed using direct compression technology. In vitro release studies indicated rapid swelling and drug release in the initial period of the acid stage from a matrix composed of chitosan and xanthan gum solely. Addition of sodium bicarbonate to the matrix resulted in sustained drug release. Various formulation factors such as polymer to polymer ratio, polymer viscosity and particle size were altered and their effect on dissolution pattern was illustrated. Manufacturing variables such as compression force and lubricant percentage were investigated and found not to influence the drug release profile of the resulted tablets. The release mechanism follows Korsmeyer-Peppas equation with n value indicating non-Fickian diffusion. The release profiles were analyzed using statistical method (one-way ANOVA) and f₂ metric values and found to be similar to the commercial product Bricanyl^®. Reproducible data were obtained when scale-up of the formulation was performed.     

马尼地平缓释片的制备及释药机制考察

目的:研制马尼地平缓释片,并考察其释药机制。方法:将制备的马尼地平固体分散体及乳糖、聚乙二醇、甲基纤维素分别过80目筛,按处方量称取,按等量递增原则于乳钵中充分混匀,干法直接压片即得。结果:马尼地平缓释片的处方组成为HPMC 60RT8000 40 mg,乳糖40 mg,聚乙二醇6000(PEG6000)40 mg,甲基纤维素(MC)80 mg。结论:该缓释片在8 h内呈现良好的零级释放特征,释放机制为骨架溶蚀机制;该缓释片在24 h内药物的释放更符合Higuchi方程,释放机制为非Fick扩散。     

Xanthan gum to tailor drug release of sustained-release ethylcellulose mini-matrices prepared via hot-melt extrusion: in vitro and in vivo evaluation.

Mini-matrices (multiple-unit dosage form) with release-sustaining properties were developed by means of hot-melt extrusion using ibuprofen as the model drug and ethylcellulose as sustained-release agent. Xanthan gum, a hydrophilic polymer, was added to the formulation to increase the drug release since ibuprofen release from the ibuprofen/ethylcellulose matrices (60/40, w/w) was too slow (20% in 24 h). Changing the xanthan gum concentration as well as its particle size modified the in vitro drug release. Increasing xanthan gum concentrations yielded a faster drug release due to a higher liquid uptake, swelling and erosion rate. Regarding the effect of the xanthan gum particle size, no difference was observed for formulations containing 10% and 20% xanthan gum. However, using 30% xanthan gum, drug release was influenced by the particle size of the hydrophilic polymer due to the susceptibility of the coarser xanthan gum particles to erosion. Drug release from the mini-matrices was mainly diffusion controlled, but swelling played an important role to obtain complete drug release within 24 h. Drug release was influenced by the ionic strength of the medium as the conformation of xanthan gum molecules is determined by the salt concentration. An oral dose of 300 mg ibuprofen was administered to dogs (n=6) in a cross-over study design either as an immediate-release preparation (Junifen), as a sustained-release formulation (Ibu-Slow 600 mg (1/2 tablet)) or as the experimental mini-matrices (varying in xanthan gum concentration). Administration of the experimental formulations sustained the ibuprofen release. Although a significant difference in dissolution rate of the 20% and 30% xanthan gum mini-matrices was detected in vitro, the difference in relative bioavailability was limited (70.6% and 73.8%, respectively).     

Design,in vitro release characterization and pharmacokinetics of novel controlled release pellets containing levodropropizine

Abstract

This study was performed to investigate the in vitro release characteristics of levodropropizine (LDP) from novel dual-coated sustained release (SR) pellets, and evaluate the pharmacokinetics of a novel controlled release (CR) preparation composed of the dual-coated SR pellets and immediate release (IR) LDP pellets. The dual-coated SR pellets composed of a drug-loaded nonpareil core, a sub-coating layer (HPMC 6cps) and an SR-coating layer (Aquacoat® ECD, Eudragit® RS 30D or Kollicoat® SR 30D) were prepared by a bottom-spray fluidized bed-coating method. The drug release from the dual-coated SR pellets coated with Aquacoat® ECD followed a zero-order profile in water, and the drug release was not affected by the coating level of the sub-coating layer and stable under the accelerated storage condition (40?°C, 75% RH) for 6 months. The CR preparation showed significantly decreased values of maximum drug concentration (C_max) and elimination rate (K) than the reference product (LEVOTUS® SYR) but the similar bioavailability (F?=?95.43%). The novel CR preparation presents promising delivery of LDP with an immediate and sustained release manner, with similar clinical effect as the commercial IR product.     

咪唑斯汀缓释片的处方工艺筛选

目的：制备一种能在5h内完全释放的咪唑斯汀缓释片。方法：以体外释放度的测定为主要考察指标，采用单因素筛选法，初步确定缓释片的处方，再对处方进一步的优化调整，确定处方中各辅料的用料量，并对缓释片的工艺在常规方法的基础上进行各项参数的优选，最后将自制缓释片与国外上市产品进行各项体外指标的对比试验。结果：其1000片配方为咪唑斯汀10mg、羟丙甲纤维素（HPMC）11．5mg、酒石酸氢钾40mg、乳糖110mg、微晶纤维素40mg、10％的乙基纤维素（EC）乙醇溶液0．068mL。结论：该处方工艺制备的咪唑斯汀缓释片能达到5h缓释的预期要求，达到了国外该制剂的同等水平，经验证适合扩大生产。