Design and evaluation of sustained release bilayer tablets of propranolol hydrochloride

The objective of the present research was to develop a bilayer tablet of propranolol hydrochloride using superdisintegrant sodium starch glycolate for the fast release layer and water immiscible polymers such as ethylcellulose, Eudragit RLPO and Eudragit RSPO for the sustaining layer. In vitro dissolution studies were carried out in a USP 24 apparatus I. The formulations gave an initial burst effect to provide the loading dose of the drug followed by sustained release for 12 h from the sustaining layer of matrix embedded tablets. In vitro dissolution kinetics followed the Higuchi model via a non-Fickian diffusion controlled release mechanism after the initial burst release. FT-IR studies revealed that there was no interaction between the drug and polymers used in the study. Statistical analysis (ANOVA) showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p < 0.05) in the amount of drug released after 12 h from optimized formulations was observed.     

Formulation and evaluation of famotidine floating tablets

The purpose of this investigation was to prepare a gastroretentive drug delivery system of famotidine. Floating tablets of famotidine were prepared employing two different grades of methocel K100 and methocel K15M by effervescent technique; these grades of methocel were evaluated for their gel forming properties. Sodium bicarbonate was incorporated as a gas-generating agent. The floating tablets were evaluated for uniformity of weight, hardness, friability, drug content, in vitro buoyancy and dissolution studies. The effect of citric acid on drug release profile and floating properties was investigated. The prepared tablets exhibited satisfactory physico-chemical characteristics. All the prepared batches showed good in vitro buoyancy. The tablet swelled radially and axially during in vitro buoyancy studies. It was observed that the tablet remained buoyant for 6-10 hours. Decrease in the citric acid level increased the floating lag time but tablets floated for longer duration. A combination of sodium bicarbonate (130mg) and citric acid (10mg) was found to achieve optimum in vitro buoyancy. The tablets with methocel K100 were found to float for longer duration as compared with formulations containing methocel K15M. The drug release from the tablets was sufficiently sustained and non-Fickian transport of the drug from tablets was confirmed.     

Design and evaluation of floating multi-layer coated tablets based on gas formation

Floating multi-layer coated tablets were designed based on gas formation. The system consists of a drug-containing core tablet coated with a protective layer (hydroxypropyl methylcellulose), a gas forming layer (sodium bicarbonate) and a gas-entrapped membrane, respectively. The mechanical properties of acrylic polymers (Eudragit^® RL 30D, RS 30D, NE 30D) and ethylcellulose were characterized by the puncture test in order to screen a suitable film for the system. Eudragit^® RL 30D was chosen as a gas-entrapped membrane due to its high flexibility and high water permeability. The obtained tablets enabled to float due to the CO₂-gas formation and the gas entrapment by polymeric membrane. The effect of formulation variables on floating properties and drug release was investigated. The floating tablets using direct-compressed cores had shorter time to float and faster drug release than those using wet-granulated cores. The increased amount of a gas forming agent did not affect time to float but increased the drug release from the floating tablets while increasing coating level of gas-entrapped membrane increased time to float and slightly retarded drug release. Good floating properties and sustained drug release were achieved. These floating tablets seem to be a promising gastroretentive drug delivery system.     

Formulation and evaluation of effervescent floating tablets of tizanidine hydrochloride

Tizanidine hydrochloride is an orally administered prokinetic agent that facilitates or restores motility through-out the length of the gastrointestinal tract. The objective of the present investigation was to develop effervescent floating matrix tablets of tizanidine hydrochloride for prolongation of gastric residence time in order to overcome its low bioavailability (34-40 %) and short biological half life (4.2 h). Tablets were prepared by the direct compression method, using different viscosity grades of hydroxypropyl methylcellulose (HPMC K4M, K15M and K100M). Tablets were evaluated for various physical parameters and floating properties. Further, tablets were studied for in vitro drug release characteristics in 12 hours. Drug release from effervescent floating matrix tablets was sustained over 12 h with buoyant properties. DSC study revealed that there is no drug excipient interaction. Based on the release kinetics, all formulations best fitted the Higuchi, first-order model and non-Fickian as the mechanism of drug release. Optimized formulation (F9) was selected based on the similarity factor (f2) (74.2), dissolution efficiency at 2, 6 and 8 h, and t50 (5.4 h) and was used in radiographic studies by incorporating BaSO4. In vivo X-ray studies in human volunteers showed that the mean gastric residence time was 6.2 ± 0.2 h.     

Preparation and evaluation of dual-mode floating gastroretentive tablets containing itraconazole

Abstract

The aims of the present study were to prepare new dual-mode floating gastroretentive tablets (DF-GRT) containing itraconazole (ITR) and to evaluate influence of the dosage forms on pharmacokinetic parameters of ITR. The solubility of ITR was enhanced around 200 times (from 1.54 to 248.38?µg/mL) by preparing solid dispersion (SD) with hydroxypropylmethyl cellulose. Buoyancy of DF-GRT containing ITR-SD was established by both camphor sublimation and gas generation. Camphor sublimation decreased density of DF-GRT by making pores in tablet matrix, which led to elimination of lag time for floating. Carbon dioxide generated by sodium bicarbonate and citric acid helped to maintain buoyancy of DF-GRT. Therefore DF-GRT floated on the medium without lag time until disintegrated entirely during in vitro release study. They released 89.11% of the drug at 2?h. Residual camphor was <0.5?wt% after sublimation. The pharmacokinetics of DF-GRT was evaluated in six miniature pigs and compared to immediate release tablets (IRT). Mean AUC ratio of GRT/IRT was 1.36 but there was no statistical difference between AUC values. However delayed t_max, increased MRT and equivalent C_max of DF-GRT supposed it could be a promising tool for gastroretentive drug delivery system containing ITR.     

HPLC法测定复方卡托普利片中卡托普利和氢氯噻嗪的含量

目的:建立高效液相色谱法同时测定复方卡托普利片中卡托普利和氢氯噻嗪的含量。方法:色谱柱为 Venusil MP-C_(18)(250 mm×4.6 mm,5 μm);流动相为乙腈-水(磷酸调节 pH 至2.2)(25:75);检测波长212 nm;柱温:55℃;流速:1.0 mL·min~(-1)。结果:卡托普利和氢氯噻嗪的线性范围分别为0.01066～0.3198 mg·mL~(-1)(r=0.9999)和0.00631～0.1893 mg·mL~(-1)(r=0.9997);平均回收率分别为99.2%(RSD=1.4%)和99.6%(RSD=0.8%)。结论:2种成分分离效果好,卡托普利二硫化物与卡托普利和氢氯噻嗪均有良好的分离度,辅料无干扰,本法简便快速,结果准确可靠,可作为该复方制剂中2种成分的质量控制方法。     

Optimisation of floating matrix tablets and evaluation of their gastric residence time

The present investigation concerns the development of the floating matrix tablets, which after oral administration are designed to prolong the gastric residence time, increase the drug bioavailability and diminish the side effects of irritating drugs. The importance of the composition optimisation, the technological process development for the preparation of the floating tablets with a high dose of freely soluble drug and characterisation of those tablets (crushing force, floating properties in vitro and in vivo, drug release) was examined. Tablets containing hydroxypropyl methylcellulose (HPMC), drug and different additives were compressed. The investigation shows that tablet composition and mechanical strength have the greatest influence on the floating properties and drug release. With the incorporation of a gas-generating agent together with microcrystalline cellulose, besides optimum floating (floating lag time, 30 s; duration of floating, >8 h), the drug content was also increased. The drug release from those tablets was sufficiently sustained (more than 8 h) and non-Fickian transport of the drug from tablets was confirmed. Radiological evidence suggests that, that the formulated tablets did not adhere to the stomach mucus and that the mean gastric residence time was prolonged (>4 h).     

马来酸曲美布汀胃漂浮缓释片的处方筛选及体外评价

目的筛选马来酸曲美布汀胃漂浮缓释片的处方,并评价其漂浮和体外释放特性。方法用正交实验设计对片剂处方进行筛选与优化,制备马来酸曲美布汀胃漂浮缓释片,测定其体外释药与漂浮特性。结果优选的处方为每片含HPMC800030 mg,CMC-Na 30 mg,十六醇70 mg,CaCO330 mg。该处方片剂在硬度为3-4 kg时漂浮性好,体外持续释药达6 h以上,符合Higuchi模型。结论该片剂具漂浮、缓释作用,制备工艺简单。     

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.     

旋光法测定卡托普利及卡托普利片含量

目的：建立卡托普利及卡托普利片含量测定方法。方法：以乙醇为溶剂,采用旋光法测定卡托普利及卡托普利片含量。结果：卡托普利在5．0～30mg／ml范围内浓度与旋光度呈良好线性关系,回归方程C=-0．0095＋0．7654X,r=1．0000,平均回收率100．3％,RSD为0．18％（n=9）。结论：本法简便易行,结果准确,可作为卡托普利及卡托普利片的质控方法。     

旋光法测定卡托普利片的含量

目的：建立一种测定卡托普利片含量的方法。方法：运用旋光法测定。结果：浓度在5－30mg.ml^-1范围内与旋光度呈线性关系,平均回收率99．9％,RSD为0．4％。结论：本法简便,快捷,准确,适有于该制剂的含量测定。     

高效液相色谱法测定复方卡托普利片剂的含量

目的用高效液相色谱法测定复方卡托普利片剂中卡托普利和氢氯噻嗪的含量。方法采用高效液相色谱法,使用Hypersil CN(150 mm×4.6 mm,5μm)色谱柱,以甲醇-四氢呋喃-水(10∶10∶80,V/V,磷酸调pH=2.86)为流动相。流速1.0 mL.min-1,检测波长220 nm。结果卡托普利在50~250μg.mL-1线性较好,其线性方程为C=1.338×10-4A-2.563(n=5,r=0.999 9);氢氯噻嗪在26~130μg.mL-1线性较好,其线性方程为C=1.804×10-5A-1.997(n=5,r=0.999 9)。卡托普利的平均回收率为100.6%,RSD=0.2%(n=6),氢氯噻嗪的平均回收率为100.6%,RSD=0.3%(n=6)。结论该方法快速简捷、可靠、准确度高、重现性好,可同时测定复方制剂中2种成分。     

Effect of antioxidants on captopril floating matrices

Stability of captopril in a controlled release formulation has been a challenge for some time. The sustained release of captopril from floating matrices has been studied varying the antioxidant load, the sodium bicarbonate proportion and the compaction pressure. Although in many cases the effect of compaction pressure remains hidden, actual results show that matrices compacted at 55?MPa have smaller density and float in the dissolution medium while those compacted at 165?MPa float only adding sodium bicarbonate. The increase of compaction pressure reduces the hydration volume and increases the time necessary to attain its maximum. These changes are attributed to lower matrix porosity and to the consequent diminution of water and drug transport. Increasing ascorbic acid proportions increase the matrix hydration volume and the drug released. The use of sodium ascorbate and the substitution of 15% polymer with sodium bicarbonate reduce the matrix hydration volume, shorten the matrix hydration process and increase the drug released. This is attributed to carbon dioxide bubbles that decrease the matrix coherence and expand the matrix volume, facilitating drug dissolution and only a limited further matrix expansion. The antioxidant protection provided by sodium ascorbate was lesser of that of ascorbic acid because of greater molecular mass and lesser release rate.     

Effect of antioxidants on captopril floating matrices

Stability of captopril in a controlled release formulation has been a challenge for some time. The sustained release of captopril from floating matrices has been studied varying the antioxidant load, the sodium bicarbonate proportion and the compaction pressure. Although in many cases the effect of compaction pressure remains hidden, actual results show that matrices compacted at 55?MPa have smaller density and float in the dissolution medium while those compacted at 165?MPa float only adding sodium bicarbonate. The increase of compaction pressure reduces the hydration volume and increases the time necessary to attain its maximum. These changes are attributed to lower matrix porosity and to the consequent diminution of water and drug transport. Increasing ascorbic acid proportions increase the matrix hydration volume and the drug released. The use of sodium ascorbate and the substitution of 15% polymer with sodium bicarbonate reduce the matrix hydration volume, shorten the matrix hydration process and increase the drug released. This is attributed to carbon dioxide bubbles that decrease the matrix coherence and expand the matrix volume, facilitating drug dissolution and only a limited further matrix expansion. The antioxidant protection provided by sodium ascorbate was lesser of that of ascorbic acid because of greater molecular mass and lesser release rate.     

卡托普利片溶出速率考察

目的：对国产及合资厂卡托普利片溶出速率的测定，考察其质量，提示国产卡托普利片有必要增加溶出度检查以控制其质量。方法：转篮法，用ＵＶ法（２１２ｎｍ）检测，提取参数（Ｔ５０、Ｔｄ、ｍ），并对参数进行相关性研究。结果：各厂产品溶出参数差异具有极显著性（Ｐ＜０．０１）；糖衣片溶出度比素片差（Ｐ＜０．０１）。     

Design and evaluation of gastroretentive mucoadhesive cephalexin tablets

The aim of this investigation was to develop gastroretentive mucoadhesive tablets of cephalexin, which will retain in the stomach for 10?h. Cephalexin, a first-generation cephalosporin, becomes ionized in intestinal pH because pKa is 4.5 and thus reducing its bioavailability. The various batches were prepared by wet granulation method using variety of mucoadhesive polymers such as hydroxyl propyl methyl cellulose K4M, hydroxyl propyl cellulose, chitosan, carbopol 934P and sodium carboxymethylcellulose and subjected to various evaluation parameters such as mucoadhesive strength, in vitro drug release profile, swelling characteristics and physical properties. It was evident from the study that the formulation containing HPMC K4M and carbopol 934P in combination exhibited maximum mucoadhesive strength of 144.42?gms, in vitro residence time was 8.73?h and in vitro drug release was found to be 75.03% in 10?h with non-Fickian diffusion mechanism. So, the optimized formulation F₂ was further subjected to in vivo retention time in rabbit by X-ray technique, SEM and Accelerated stability studies. Regarding all the properties evaluated, the formulation containing HPMC K4M and carbopol 934P in combination was found to be the best to achieve the aim of this study.     

芍药苷胃漂浮片的制备

目的 制备芍药苷胃漂浮片,优选芍药苷胃漂浮片的制备工艺。方法 采用湿法制粒压片制备芍药苷胃漂浮片,以漂浮性能和体外累积释放率为考查指标,采用单因素筛选及正交设计法,优化芍药苷胃漂浮片处方。结果 以HPMC K4M(20%)为骨架材料、NaHCO₃(15%)为起泡剂、PVPP(7%)为释放促进剂、乳糖200为填充剂制得的胃漂浮片能立即起漂,持续漂浮12 h以上,累积释放率达90%以上。结论 优选的芍药苷胃漂浮片达到了持续漂浮及缓慢释放的要求,可操作性强。     

卡托普利片质量标准的改进

目的:对2005年版中国药典收载的卡托普利片中卡托普利二硫化物检查及溶出度检查的方法进行改进,并建立 HPLC法测定卡托普利片含量。方法:采用 Phenomenex C_(18)柱(4.6 mm×250 mm,5μm);流动相:9%四氢呋喃甲醇溶液-0.05%磷酸溶液(42∶58),用三乙胺调节 pH 至3.0;流速:1.0 mL·min~(-1);检测波长:215 nm。柱温:室温。结果:卡托普利二硫化物线性范围4.06～64.90μg·mL~(-1)(r=1.000);低、中、高浓度平均回收率(n=3)分别为99.5%,99.8%,99.9%,RSD 分别为1.3%,1.1%,0.9%。卡托普利含量测定及溶出度检查线性范围17.29～172.92μg·mL~(-1)(r=1.000);低、中、高浓度回收率(n=3)分别为100.4%,100.1%,99.7%,RSD 分别为0.21%,0.19%,0.27%。结论:本法准确、灵敏、简便,适用于卡托普利片质量控制。     

当归多糖铁胃内漂浮缓释片的处方筛选及体外评价

目的:研究当归多糖铁胃内漂浮缓释片(APIC-FSRT)的制备工艺及释放机理.方法:采用均匀设计优化处方,以丙烯酸树脂Ⅱ,羟丙基甲基纤维素,聚维酮等为辅料,全粉末直接压片.结果:筛选出体外释放10 h,漂浮达12 h的最优化处方,其释放曲线符合Higuchi方程.结论:为制备当归多糖铁胃内漂浮缓释片提供依据.     

Design and evaluation of fast dissolving tablets of clonazepam

In the present work, fast dissolving tablets of clonazepam were prepared by direct compression method with a view to enhance patient compliance. Three super-disintegrants, viz., crospovidone, croscarmellose sodium and sodium starch glycolate in different ratios with microcrystalline cellulose (Avicel PH-102) along with directly compressible mannitol (Pearlitol SD 200) to enhance mouth feel. The prepared batches of tablets were evaluated for hardness, friability, drug content uniformity, wetting time, water absorption ratio and in vitro dispersion time. Based on in vitro dispersion time (approximately 13 s), three formulations were tested for the in vitro drug release pattern (in pH 6.8 phosphate buffer), short-term stability (at 40°/75% relative humidity for 6 mo) and drug-excipient interaction (IR spectroscopy). Among the three promising formulations, the formulation prepared by using 10% w/w of crospovidone and 35% w/w of microcrystalline cellulose emerged as the overall best formulation (t(50%) 1.8 min) based on the in vitro drug release characteristics compared to conventional commercial tablet formulation (t(50%) 16.4 min). Short-term stability studies on the formulations indicated that there were no significant changes in drug content and in vitro dispersion time (P<0.05).