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.     

阿魏酸钠胃漂浮缓释片的制备及体外释放

目的:制备阿魏酸钠胃漂浮片,评价其体外释药性能。方法:以羟丙基甲基纤维素(HPMC)为亲水性凝胶骨架,碳酸氢钠为起泡剂,采用粉末直接压片方法制备漂浮片,以释放度、漂浮性能以及外观作为考察指标,进行处方筛选,并考察了制备方法和HPMC规格对体外释药的影响。结果:优化处方持漂时间达8 h,8 h体外累积释放度达到62%,显著高于市售普通片体外释放度的49%。结论:优化处方的阿魏酸钠胃漂浮片具有起漂时间快、缓释效果明显的特点。     

Effect of formulation parameters on the drug release and floating properties of gastric floating two-layer tablets with acetylsalicylic acid

Floating dosage forms of acetylsalicylic acid, used for its antithrombotic effect, were developed to prolong gastric residence time and increase bioavailability. In the two-layer tablet formulation, hydroxypropyl methylcellulose (HPMC) of high viscosity and an effervescent mixture of citric acid and sodium bicarbonate formed the floating layer. The release layer contained the drug, direct tableting agent and different types of matrix-forming polymers such as HPMC of low viscosity, sodium carboxymethylcellulose and chitosan. Tablets were prepared using a direct compression technique. The effect of formulation variables on physicochemical and floating properties and the drug release from tablets were investigated. Floating ability was dependent on the amount of effervescent agent and gel-forming polymer of the floating layer. Drug release was prolonged to 8 hours by changing the type and viscosity of the matrix-forming polymer in the drug-loading layer and all formulations showed a diffusion release mechanisms.     

Oral controlled release formulations of rifampicin. Part II: Effect of formulation variables and process parameters on in vitro release

Hydrophilic controlled release matrix tablets of rifampicin, a poorly soluble drug, have been formulated using hydroxypropyl methylcellulose (HPMC) polymer (low, medium, and high viscosity) by direct compression method. Influence of formulation variables and process parameters such as drug:HPMC ratio, viscosity grade of HPMC, drug particle size, and compression force on the formulation characters and drug release has been studied. Our results indicated that the release rate of the drug and the mechanism of release from the HPMC matrices are mainly controlled by the drug:HPMC ratio and viscosity grade of the HPMC. In general, decrease in the drug particle size decreased the drug release. Lower viscosity HPMC polymer was found to be more sensitive to the effect of compression force than the higher viscosity. The formulations were found to be stable and reproducible.     

Development and release mechanism of diltiazem HCl prolonged release matrix tablets

A coated matrix tablet formulation has been used to develop controlled release diltiazem HCl (DIL) tablets. The developed drug delivery system provided prolonged drug release rates over a defined period of time. DIL tablets prepared using dry mixing and direct compression and the core consisted of hydrophilic and hydrophobic polymers such as hydroxypropylmethylcellulose (HPMC), Eudragits RLPO/RSPO, microcrystalline cellulose, and lactose. Tablets were coated with Eudragit NE 30D, and the influence of varying the inert hydrophobic polymers and the amount of the coating polymer were investigated. The release profile of the developed formulation was described by the Higuchi model. Stability trials up to 6 months displayed excellent reproducibility.     

Effects of formulation and process variables on the release of a weakly basic drug from single unit extended release formulations.

A new commercially available extended release matrix material, Kollidon SR, composed of polyvinylacetate (PVA) and polyvinylpyrrolidone (PVP), was evaluated with respect to its ability to modulate the in vitro release of the weakly basic drug ZK 811 752. The effect of different formulation and process parameters on the release kinetics of ZK 811 752 from PVA/PVP based matrix tablets was investigated as a function of the (i) nature of excipient added to the drug-polymer mixtures, (ii) method of manufacturing (direct compression versus wet granulation), and (iii) effect of a post-compression curing step. ZK 811 752 containing extended release matrix tablets were successfully prepared by using Kollidon SR. The drug release from the matrix tablets increased by the addition of excipients such as maize starch, lactose and calcium phosphate. Addition of the highly swellable maize starch and the water-soluble lactose accelerated the drug release in a more pronounced manner compared to the water-insoluble calcium phosphate. Compound release from matrix tablets prepared by wet granulation was faster compared to the drug release from tablets prepared by direct compression. Post compression curing did not influence the drug release rate from drug-lactose-Kollidon SR formulations. Stability studies demonstrated no degradation of the drug substance and reproducible drug release patterns for matrix tablets stored at 25 degrees C/60% RH and 30 degrees C/70% RH for up to 6 months.     

Improvement of photostability and dissolution profile of isradipine using inclusion complex

Inclusion complexes using β-cyclodextrin were manufactured by solvent evaporation method. Then, sustained release (SR) hydroxypropylmethylcellulose (HPMC) matrix tablets containing inclusion complex were prepared via direct compression. Isradipine was chosen as a model drug due to its low solubility, photo-instability and short elimination half-life. The physicochemical properties of the inclusion complexes were examined using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The solubility test and dissolution behaviours were also investigated. Based on the solubility experiments, a 1:2 molar ratio (isradipine:β-Cyclodextrin) was best and chosen to prepare inclusion complexes. In addition, the crystal structure of isradipine was converted to an amorphous structure, as confirmed by Fourier transform infrared spectroscopy (FT-IR) and DSC. The photostability of isradipine in the inclusion complex was more stable than pure isradipine after 4 days radiation. By using hypromellose as the hydrophilic sustained release material, the dissolution rate was retarded during 24 h. A combined method of inclusion complex and SR technology showed increased and sustained release profile above that of Dynacirc^® SR Cap. 5 mg.     

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.     

卡托普利亲水凝胶缓释片的制备及体外释放影响因素

目的 :制备卡托普利亲水凝胶缓释片 ,并考察其体外释放影响因素。方法 :以羟丙基甲基纤维素为骨架材料 ,粉末直接压片制备卡托普利缓释片。以释放度为指标 ,评价多种因素对释放度的影响。结果与结论 :制得片剂体外释药行为符合Higuchi方程 ;羟丙基甲基纤维素用量达15 %即有缓释效果 ,用量为60 %时缓释效果最佳 ;MethocelK系列比60RT、75RT系列释放慢 ;填充剂以乳糖为佳 ,提高填充剂用量可明显减慢卡托普利的释放 ;浆法较转篮法释放略快 ;压片力和释放介质 pH值对溶出无明显影响。     

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.     

星点设计-效应面法优化尼可地尔胃漂浮缓释片制剂处方

目的:应用星点设计-效应面法对尼可地尔胃漂浮缓释片进行处方优化。方法:采用粉末直接压片法,以制剂辅料中HPMC、十八醇和碳酸氢钠的用量为考察因素,以1,4,8 h的累积释放度和漂浮性能为评价指标,应用星点设计-效应面法优化制剂处方,并对胃漂浮缓释片释药机理做初步研究。结果:最佳制剂处方为:HPMC 60 mg、十八醇40 mg、碳酸氢钠30 mg;经处方验证,体外累积释放度的预测值与实测值偏差<5%,起漂时间<5 min,续漂时间>8 h;经Ritger-Peppas方程拟合,n=0.5357,提示该缓释片体外释放为非Fick扩散,具扩散与骨架溶蚀的双重机制。结论:应用星点设计-效应面法优选出了最佳制剂处方,按最佳制剂处方制备的尼可地尔胃漂浮缓释片具有良好的漂浮性能和缓释特性,制备方法简便。     

双氯芬酸钾羟丙基甲基纤维素骨架片体外释药的影响因素

目的考察影响双氯芬酸钾羟丙基甲基纤维素(HPMC)骨架片体外释放的各种因素。方法以HPMC为骨架材料,采用湿颗粒法制备双氯芬酸钾缓释片,考察药物/HPMC比、HPMC黏度、HPMC粒径、释放介质pH、压片压力及桨转速对药物体外释放行为的影响。结果药物/HPMC比、HPMC黏度和释放介质pH显著影响双氯芬酸钾释药速率,HPMC粒径、压片压力和桨转速对双氯芬酸钾释药速率影响较小。结论通过使用合适黏度的HPMC及调节药物/HPMC比可获得具有理想释药行为的双氯芬酸钾HPMC缓释片。     

盐酸普萘洛尔脉冲释放片的制备及其体外释药研究

目的 制备盐酸普萘洛尔双层包衣脉冲释放片,并研究其体外释药行为。方法 采用粉末直接压片法制备盐酸普萘洛尔片芯,滚转包衣锅法分别包羟丙甲纤维素溶胀层和丙烯酸树脂控释层。采用体外溶出试验考察处方及溶出条件对本品释药行为的影响。结果 本品经过一定时滞后以脉冲形式释药,渗透活性物质氯化钠、溶胀层及控释层厚度、丙烯酸树脂RS/RL的配比均影响本品时滞。溶出方法及不同pH溶出介质对本产品的时滞无影响。结论 盐酸普萘洛尔脉冲释放片具有脉冲释放特性,体外时滞约为4 h。     

阿魏酸钠双层片的制备及体外释放特性

目的:制备阿魏酸钠双层片并考察其体外释放特性.方法:采用粉末直接压片法,以羟丙基甲基纤维素(HPMC)为骨架材料制备阿魏酸钠双层片,通过紫外分光光度法,按照<中国药典>的转篮法测定体外释放度,并对体外药物释放的影响因素进行考察.结果:HPMC的规格和用量是影响药物释放的主要因素,填充剂不同对药物的释放也产生一定影响.结论:以HPMC K15M为骨架材料,微晶纤维素为填充剂制备的阿魏酸钠双层片具有良好的缓释和速释特性.     

Formulation and Optimization of a Sustained-Release Tablet of Ketorolac Tromethamine

The objective of our study was to formulate a sustained-release tablet of Ketorolac tromethamine, which is a nonsteroidal anti-inflammatory agent. A 2 3 full factorial design (8 runs) was selected. The variables studied were the amount of drug (30 and 40 mg), ratio of hydroxypropyl methylcellulose (HPMC)/sodium carboxymethylcellulose (NaCMC) (240/40 and 140/140 mg), and amount of ethylcellulose (140 and 180 mg). Swelling-controlled matrix tablets were manufactured by direct compression of formulation ingredients using a Stokes single punch tablet press. Dissolution tests were performed using USP apparatus 3 (Bio-Dis II), at various pHs to mimic the conditions that exist in the gastrointestinal tract. Responses studied included time for 50% of the drug to dissolve (T 50), diffusional exponent (n) that characterizes the release mechanism, and percent friability of the tablets. Analysis of variance indicated that the release rate (T 50) was affected by the HPMC/NaCMC ratio, amount of drug, and two-way and three-way interactions; whereas the amount of drug, HPMC/NaCMC ratio, ethylcellulose, and the interaction between drug and HPMC/NaCMC and HPMC/NaCMC and ethylcellulose and also three-way interactions were significantly affecting the diffusional exponent (n) . The release mechanism was found to be super-case II transport. The friability of the tablets was significantly affected by all three factors: amount of drug, HPMC/NaCMC ratio, and amount of ethylcellulose. The formulation giving the best release characteristics was identified.     

In vitro controlled release of alfuzosin hydrochloride using HPMC-based matrix tablets and its comparison with marketed product

The present study is an attempt to formulate a controlled-release matrix tablet formulation for alfuzosin hydrochloride by using low viscous hydroxy propyl methyl cellulose (HPMC K-100 and HPMC 15cps) and its comparison with marketed product. Different batches of tablets containing 10 mg of alfuzosin were prepared by direct compression technique and evaluated for their physical properties, drug content, and in vitro drug release. All the formulations had a good physical integrity, and the drug content between the batches did not vary by more than 1%. Drug release from the matrix tablets was carried out for 12 hr and showed that the release rate was not highly significant with different ratios of HPMC K-100 and HPMC15cps. Similar dissolution profiles were observed between formulation F3 and the marketed product throughout the study period. The calculated regression coefficients showed a higher r2 value with zero-order kinetics and Higuchi model in all the cases. Although both the models could be applicable, zero-order kinetics seems to be better. Hence, it can be concluded that the use of low viscous hydrophilic polymer of different grades (HPMC K-100 and HPMC 15cps) can control the alfuzosin release for a period of 12 hr and was comparable to the marketed product.     

Formulation and optimization of a sustained-release tablet of ketorolac tromethamine

The objective of our study was to formulate a sustained-release tablet of Ketorolac tromethamine, which is a nonsteroidal anti-inflammatory agent. A 2 3 full factorial design (8 runs) was selected. The variables studied were the amount of drug (30 and 40 mg), ratio of hydroxypropyl methylcellulose (HPMC)/sodium carboxymethylcellulose (NaCMC) (240/40 and 140/140 mg), and amount of ethylcellulose (140 and 180 mg). Swelling-controlled matrix tablets were manufactured by direct compression of formulation ingredients using a Stokes single punch tablet press. Dissolution tests were performed using USP apparatus 3 (Bio-Dis II), at various pHs to mimic the conditions that exist in the gastrointestinal tract. Responses studied included time for 50% of the drug to dissolve ( T 50 ), diffusional exponent ( n ) that characterizes the release mechanism, and percent friability of the tablets. Analysis of variance indicated that the release rate ( T 50 ) was affected by the HPMC/NaCMC ratio, amount of drug, and two-way and three-way interactions; whereas the amount of drug, HPMC/NaCMC ratio, ethylcellulose, and the interaction between drug and HPMC/NaCMC and HPMC/NaCMC and ethylcellulose and also three-way interactions were significantly affecting the diffusional exponent ( n ). The release mechanism was found to be super-case II transport. The friability of the tablets was significantly affected by all three factors: amount of drug, HPMC/NaCMC ratio, and amount of ethylcellulose. The formulation giving the best release characteristics was identified.     

Floating matrix dosage form for propranolol hydrochloride based on gas formation technique: development and in vitro evaluation

Gastroretentive tablets of propranolol hydrochloride were developed by direct compression method using citric acid and sodium bicarbonate as the effervescent base. Hydroxypropyl methylcellulose; HPMC K15M was used to prepare the floating tablets to retard the drug release for 12h in stomach. Na-carboxymethyl cellulose (NaCMC) or carbopol 934P was added to alter the drug release profile or the dimensional stability of the formulation. Dicalcium phosphate (DCP) was used as filler. Formulations were evaluated for floating lag time, duration of floating, dimensional stability, drug content and in vitro drug release profile. The formulations were found to have floating lag time less than 1min. It was found that the dimensional stability of the formulations increase with increasing concentration of the swelling agent. The release mechanism of propranolol hydrochloride from floating tablets was evaluated on the basis of Peppas and Higuchi model. The ana value of the formulations ranged from 0.5201 to 0.7367 (0.5相似文献   

使用亲水性聚合物调节硝苯地平从缓释骨架片中的释放(英文)

目的根据体外释放曲线调节硝苯地平缓释片(20 mg)的药物释放特性同时评价不同羟丙甲纤维素(HPMC)作为骨架材料的作用。方法硝苯地平HPMC骨架片使用不同粘度的HPMC和其他辅料由湿法制粒后压片制得。自制制剂和参比制剂的释放曲线采用美国药典中桨法进行评价,硝苯地平药物含量采用高效液相色谱法进行测定。结果使用不同的骨架材料药物的释放具有显著性差异,通过改变HPMC的种类调节和控制硝苯地平的释放。聚合度相同,与低粘度的HPMC(K4M,K100LV,E5)相比高粘度的HPMC(K15M)会使硝苯地平释放变慢。最终的处方用10 mg K4M作为主要的骨架材料,10 mg PVP K30作为释药调节剂。结论制备硝苯地平缓释片使用骨架材料HPMC K4M和释药调节剂PVP K30;口服缓释剂型可以改善慢性治疗顺应性并且可维持有效血药浓度。