Formulation and Evaluation of Cefixime Trihydrate Matrix Tablets Using HPMC,Sodium CMC,Ethyl Cellulose

The objective of the present work is to design sustained release matrix tablets of cefixime trihydrate by incorporating drug in a matrix made up of release retardant polymers, which prolong drug release leading to minimization of the peak and valley effect in the plasma and provide patient convenience. The effect of combination of polymers on parameters like release pattern, release mechanism of the drug were studied. Total nine formulations each containing 200 mg of drug were prepared by direct compression method. The formulations F-1, F-2, F-3 were prepared with a 1:1 drug to polymer ratio using hydroxypropyl methylcellulose, carboxymethyl cellulose sodium and ethyl cellulose. F-4 was prepared with a 1:1 ratio of hydroxypropyl methylcellulose, carboxymethyl cellulose sodium, F-5 as prepared with a 1:1 ratio of hydroxypropyl methylcellulose and ethyl cellulose, F-6 was prepared with a 1:1 ratio of carboxymethyl cellulose sodium and ethyl cellulose, F-7, F-8, F-9 were prepared by using polymers hydroxypropyl methylcellulose, carboxymethyl cellulose sodium and ethyl cellulose in the ratios of 0.5:0.5:1, 0.5:1:0.5, and 1:0.5:0.5. Designed matrix tablets were evaluated for various pre-compression and post-compression parameters. Formulation F-5 showed 102.15 % release at the end of 12 h and it is selected as the best formulation. All Formulations followed zero order with non-Fickian diffusion method.     

Effect of Different Polymer Concentration on Drug Release Rate and Physicochemical Properties of Mucoadhesive Gastroretentive Tablets

Mucoadhesive tablets have emerged as potential candidates for gastroretentive drug delivery providing controlled release along with prolonged gastric residence time. Gastroretentive mucoadhesive tablets could result in increased bioavailability due to prolonged gastric residence time. A hydrophilic matrix system was developed as mucoadhesion is achievable on appropriate wetting and swelling of the polymers used. The polymers were so chosen so as to provide a balance between swelling, mucoadhesion and drug release. The polymers chosen were hydroxypropyl methylcellulose K4M, chitosan, and Carbopol 934. The concentrations of these polymers used has a great impact on the physicochemical properties of the resulting formulation. The tablets were formulated using wet granulation method and tranexamic acid was used as the model drug. The prepared tablets were characterized for size, shape, appearance, hardness, friability, weight variation, swelling, mucoadhesion and in vitro drug release. Several batches of tablets were prepared by varying the ratio of hydroxypropyl methylcellulose K4M and Chitosan. The batches having a greater ratio of chitosan showed higher rate of swelling, greater erosion, less mucoadhesion and faster release rate of the drug whereas the batches having greater ratio of hydroxypropyl methylcellulose K4M showed lesser rate of swelling, less erosion, better mucoadhesion and a smaller drug release rate. The level of carbopol was kept constant in all the batches.     

A possible application of magnetic resonance imaging for pharmaceutical research

Magnetic resonance imaging (MRI) is a non-destructive and non-invasive method, the experiment can be conducted in situ and allows the studying of the sample and the different processes in vitro or in vivo. 1D, 2D or 3D imaging can be undertaken. MRI is nowadays most widely used in medicine as a clinical diagnostic tool, but has still seen limited application in the food and pharmaceutical sciences. The different imaging pulse sequences of MRI allow to image the processes that take place in a wide scale range from ms (dissolution of compact tablets) to hours (hydration of drug delivery systems) for mobile as well as for rigid spins, usually protons. The paper gives examples of MRI application of in vitro imaging of pharmaceutical dosage based on hydroxypropyl methylcellulose which have focused on water-penetration, diffusion, polymer swelling, and drug release, characterized with respect to other physical parameters such as pH and the molecular weight of polymer. Tetracycline hydrochloride was used as a model drug. NMR imaging of density distributions and fast kinetics of the dissolution behavior of compact tablets is presented for paracetamol tablets.     

Modulation of Venlafaxine Hydrochloride Release from Press Coated Matrix Tablet

The aim of present study was to prepare novel modified release press coated tablets of venlafaxine hydrochloride. Hydroxypropylmethylcellulose K4M and hydroxypropylmethylcellulose K100M were used as release modifier in core and coat, respectively. A 3² full factorial design was adopted in the optimization study. The drug to polymer ratio in core and coat were chosen as independent variables. The drug release in the first hour and drug release rate between 1 and 12 h were chosen as dependent variables. The tablets were characterized for dimension analysis, crushing strength, friability and in vitro drug release. A check point batch, containing 1:2.6 and 1:5.4 drug to polymer in core and coat respectively, was prepared. The tablets of check point batch were subjected to in vitro drug release in dissolution media with pH 5, 7.2 and distilled water. The kinetics of drug release was best explained by Korsmeyer and Peppas model (anomalous non-Fickian diffusion). The systematic formulation approach enabled us to develop modified release venlafaxine hydrochloride tablets.     

Assessment of bioavailability of experimental single-unit sustained release tablets of verapamil hydrochloride using the stable isotope technique

A stable isotope technique has been used to assess the bioavailability of sustained release verapamil products. The test formulations were tablets with a core containing 90 mg of verapamil hydrochloride coated with ethylcellulose film, the permeability of which was controlled using different amounts of hydroxypropyl methylcellulose. A product containing ethylcellulose 75% hydroxypropyl methylcellulose 25% w/w gave a single-unit sustained release tablet of verapamil hydrochloride that allowed a dose interval of 24 h. There was no loss in bioavailability, even though verapamil had extensive first-pass metabolism.     

Tablets of paliperidone using compression-coated technology for controlled ascending release

The aim of this work was to prepare ascending release compression-coated (CC) tablets with paliperidone (PAL) using a simple manufacturing technique and short manufacturing process. The release behavior and mechanisms in vitro of the final tablets was investigated and evaluated. The PAL CC tablets were comprised of a core layer of high viscosity hydroxypropyl cellulose (HPC-H) and a coating layer of high viscosity hydroxypropyl methylcellulose (HPMC-K100M). Several factors such as materials and core tablet compositions were studied for their influence in the formulation procedure. The drug release mechanism was studied using gravimetric analysis. The data could be fitted to the Peppas model. The ascending drug release results were expressed in terms of the slope of the release curve at different time points. Results showed that the formulation could achieve a good ascending drug release when the weight ratio of PAL was 5:1 (core:layer). The fraction of HPC and HPMC was 33 %, and the combination of Eudragit RL-PO was 10%. The ascending release mechanism was due to solvent penetration into the PAL CC tablets, and subsequent drug dissolution from the gelatinous HPC and HPMC matrix erosion. The release mechanism was therefore a combination of diffusion and erosion. This work demonstrated that the compression-coated tablets could achieve controlled ascending release over 24 h for the oral administration systems.     

Design and in vitro testing of a floatable gastroretentive tablet of metformin hydrochloride

Metformin hydrochloride, which is better absorbed in the upper intestine, was formulated as a floating (buoyant) matrix tablet using a gas generating agent (sodium bicarbonate) and a gel forming hydrophilic polymer (hydroxypropyl methylcellulose). The formulation was optimized on the basis of floating ability and in vitro drug release. The resulting formulation produced robust tablets with optimum hardness, consistent weight uniformity and low tablet friability. All tablets but one exhibited satisfactory (gradual and near complete) drug release and buoyancy. In vitro drug release tests of these tablets indicated controlled sustained release of metformin hydrochloride and 96-99% released at the end of 8 h. Two formulations of fabricated tablets containing metformin hydrochloride (500 mg), sodium bicarbonate (75 mg), hydroxypropyl methylcellulose-K 4M (170-180 mg), citric acid (between 15 and 20 mg) and polyvinyl pyrrolidone K90 (32-40 mg) with hardness between 6.8 to 7.5 kg/cm2 showed a floating time of more than 8 h and promising drug release results. The release followed the Higuchi kinetic model, indicating diffusion dominated drug release.     

羟丙基甲基纤维素的凝胶特性及其对曲尼司特缓释片释放行为的影响

目的：研究羟丙基甲基纤维素(HPMC)的凝胶特性及其对曲尼司特缓释片释放行为的影响。方法：采用称重法、图像法和体积测量法,研究HPMC辅料片和曲尼司特缓释片在不同pH环境中的水合度和溶胀度。结果：辅料片在SGF和SIF中的水合速率常数分别为0.897 h-1和0.681 h-1;溶胀速率常数分别为1.005 h^-1和0.713 h^-1。曲尼司特缓释片在SGF中,在0.5 h内迅速水合和溶胀,其后呈负增长;而在SIF中,重量和体积都缓慢增加,5 h后重量稍有下降,体积保持不变。结论：HPMC水凝胶的形成速度和形态与介质的pH有关,凝胶层的溶蚀速度控制药物的释放。     

盐酸丁螺环酮缓释片的制备及其体外释放研究

目的:制备盐酸丁螺环酮缓释片,并考察其释药行为及其影响因素。方法:采用羟丙基甲基纤维素(HPMC)为亲水凝胶骨架材料,乙基纤维素(EC)为阻滞剂,湿法制粒制备盐酸丁螺环酮缓释片。考察不同释放递质,HPMC、EC的不同含量及不同黏度对该缓释片体外释放的影响。结果:制备出的缓释片24h的释药量超过90%,释药速率符合Higuchi方程。HPMC、EC含量的增加均会减慢缓释片的释放;随着HPMC黏度的增大,片剂的释药速率减慢,而EC的黏度及释放递质对释药速率均无明显影响。结论:以HPMC和EC为骨架材料,能制备出持续释药24h的盐酸丁螺环酮缓释片。     

Psyllium: a promising polymer for sustained release formulations in combination with HPMC polymers

Abstract

Psyllium has a mucilaginous property that makes it a good candidate to be utilized as an excipient in the preparation of controlled release systems. Various formulations were prepared using theophylline as a model drug and investigated with a view to achieve an ideal slow drug release profile. The addition of hydroxypropyl methylcellulose (HPMC) to psyllium significantly reduced the burst release; however, the percentage of drug release within a 12?h period was too slow and thereby inadequate. This was overcome by the addition of lactose as a hydrophilic filler that enabled a slow release with roughly 80% drug release in 12?h. The inclusion of HPMC within psyllium formulations changed the drug release kinetics from Fickian diffusion to anomalous transport. Granulated formulations demonstrated slower drug release than ungranulated or physical mixture and caused a change in the dissolution kinetics from Fickian diffusion to anomalous transport. Milled granules showed more efficient controlled drug release with no burst release. Milling of the granules also changed the drug release kinetics to anomalous transport. Although psyllium was proved to be a promising polymer to control the drug release, a combination of psyllium-HPMC and formulation processes should be considered in an attempt to achieve a zero-order release.     

Influence of HPMC K100LV and Compritol® HD5 ATO on Drug Release and Rheological Behavior of HPMC K4M Matrix Tablets

Purpose

The objectives of this study were to develop once-a-day oral controlled-release tablets of quetiapine fumarate (QF) and to determine the effect of polymer type, viscosity grade, polymer ratio, and polymer rheological properties on the rate of QF release from hydroxypropyl methylcellulose (HPMC) matrix tablets.

Methods

Tablets were prepared from low-viscosity-grade HPMC K100LV (K100LV), high-viscosity-grade HPMC K4M (K4M), Compritol® HD5 ATO (PEGylated glyceryl behenate (PGB)), and binary combinations of these polymers. In vitro drug release from all tablets was evaluated over 24 h.

Results

In vitro drug release studies revealed that formulations containing K100LV/K4M and PGB/K4M at a ratio of 170:70 resulted in similar release profiles which extended for 24 h (f2 > 50). QF release kinetics followed either diffusion, anomalous transport, case II transport, or super case II transport, as fitted by the Korsmeyer-Peppas model. Tablet swelling and erosion studies were consistent with dissolution profiles. A linear relationship between % swelling and % QF released was observed in tablets containing K4M alone or in combination with K100LV or PGB, indicating the direct role of polymer swelling in controlling the mechanism of drug release. The viscoelastic properties of single and binary polymeric gels made with the three polymers (K100LV, K4M, and PGB) corroborated the in vitro release studies of QF tablets.

Conclusions

Our results provide evidence that blending polymers with different viscosities and hydrophilicities can result in unique matrices with tunable release profiles.

     

The physicodynamic properties of mucoadhesive polymeric films developed as female controlled drug delivery system

Phenoporlamine hydrochloride is a novel compound that is used for the treatment of hypertension. The purpose of this study was to develop a sustained release tablet for phenoporlamine hydrochloride because of its short biological half-life. Three floating matrix formulations of phenoporlamine hydrochloride based on gas forming agent were prepared. Hydroxypropyl methylcellulose K4M and Carbopol 971P NF were used in formulating the hydrogel drug delivery system. Incorporation sodium bicarbonate into matrix resulted in the tablet floating over simulated gastric fluid for more than 6 h. The dissolution profiles of all tablets showed non-Fickian diffusion in simulated gastric fluid. Moreover, release of the drug from these tablets was pH-dependent. In vivo evaluations of these formulations of phenoporlamine hydrochloride were conducted in six healthy male human volunteers to compare the sustained release tablets with immediate release tablets. Data obtained in these studies demonstrated that the floating matrix tablet containing more Carbopol was capable of sustained delivery of the drug for longer periods with increased bioavailability and the relative bioavailability of formulation (containing 25% Carbopol 971P NF, 8.3% HPMC K4M) showed the best bioequivalency to the reference tablet (the relative bioavailability was 1.11 ± 0.19).     

盐酸曲马多多层控释骨架片的体外释药规律

以羟丙基甲基纤维素为主要骨架材料 ,将高水溶性药物盐酸曲马多制成多层控释骨架片 ,研究了影响多层骨架片体外释药速率的因素。结果表明 ,通过改变盐酸曲马多多层骨架片各层组成 ,可以灵活地改变其释药速率。多层骨架片系统可以避免初始的突释现象 ,而且其体外释药规律可以接近零级。因此 ,多层骨架片系统是制备高水溶性药物控释制剂的有效方法     

Influence of beta-cyclodextrin complexation on carbamazepine release from hydroxypropyl methylcellulose matrix tablets.

The in vitro release profiles of carbamazepine and beta-cyclodextrin either complexed or simply mixed and subsequently incorporated in hydrophilic matrix tablets containing 15 or 30% hydroxypropyl methylcellulose were evaluated. Solubility studies revealed a linear relationship between the increase in carbamazepine solubility and the increase in beta-cyclodextrin concentration. Drying methods (spray-drying and freeze-drying) were used to obtain carbamazepine/beta-cyclodextrin solid complexes in order to prepare tablets. The results demonstrated that matrix tablets containing carbamazepine/beta-cyclodextrin solid complexes displayed faster carbamazepine and beta-cyclodextrin release compared to that containing simple physical mixture. Gelling and matrix formation was impaired in formulation containing 15% hydroxypropyl methylcellulose and spray-dried complex. The comparison of spray-drying and freeze-drying revealed no significant influence of both drying methods on carbamazepine and beta-cyclodextrin dissolution rate when carbamazepine/beta-cyclodextrin complexes were incorporated in 30% hydroxypropyl methylcellulose matrix tablets. The results point to the possibility of modulating carbamazepine release using a hydroxypropyl methylcellulose matrix associated to the drug complexed with beta-cyclodextrin.     

Preparation and evaluation of a novel delayed-onset sustained-release system of propranolol hydrochloride

The objective of this work was to prepare and evaluate a new delayed-onset sustained-release system, comprising a sustained-release core tablet with hydroxypropyl methylcellulose as polymer matrix and an ethylcellulose/Eudragit L coating capable of delaying the drug release. The sustained core containing propranolol hydrochloride as the model drug was prepared by granulate tableting and the polymer coating was applied in a computer-controlled coating pan. The dissolution tests demonstrated that the in-vitro drug release was pH-dependent with sufficient gastric resistance, and the lag time (t(10%)) could be controlled by adjusting the coating level. Three dosage forms including commercial tablet, sustained-release tablet and the delayed-onset sustained-release tablet were administrated to six beagle dogs and the plasma levels of propranolol hydrochloride were measured with high-performance liquid chromatography. The delayed-onset sustained-release tablet had a lag time of 3.0 h in-vitro and 3.5 h in-vivo, and a t(max) of 7.0 h. The relative bioavailability for delayed-onset sustained-release tablet was 96.98% compared with commercial tablets. The results indicate that the new propranolol delayed-onset sustained-release system could achieve a relatively constant drug release followed by a programmed lag time, and this may provide a promising drug delivery form for chronopharmacotherapy of certain cardiovascular diseases.     

Sustained release of acetaminophen from a heterogeneous mixture of two hydrophilic non-ionic cellulose ether polymers

This study examined the release of acetaminophen (APAP) from hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) matrices. The effect of pseudoephedrine (PE) as a co-active, HPMC:HPC ratio, polymer loading, pH of the dissolution media, and compression force on APAP release were studied. Granules formulated with APAP or both APAP and PE, and various blends of HPMC and HPC were compressed into tablets at different compression forces. APAP release from the matrix tablets was not considerably influenced by changes in HPMC:HPC ratio or compression force. The rate of drug release was significantly affected by pH of the dissolution media, total polymer loading, and the presence of PE. Drug release from the formulations containing both APAP and PE was slower than those containing only APAP. Drug release from tablets formulated with APAP only showed an initial burst at pH 1.16 or 7.45. Formulations containing both APAP and PE showed slower drug release at pH 1.16 than at pH 7.4. The drug release data showed a good fit to the Power Law Model. The mechanism of drug release is consistent with a complex behavior. The results of the tablet erosion studies indicated that the amount of APAP released was linearly related to the percentage of tablet weight loss. The kinetics of tablet water uptake was consistent with a diffusion and stress relaxation mechanism.     

Role of chitosan on controlling the characteristics and antifungal activity of bioadhesive fluconazole vaginal tablets

Vaginal fluconazole (FLZ) prolonged release tablets containing chitosan in physical blends with other bioadhesive polymers were designed. Chitosan was mixed with hydroxypropyl methylcellulose (HPMC), guar gum or sodium carboxymethyl cellulose (NaCMC) at different ratios and directly compressed into tablets. In-vitro release profiles of FLZ were monitored at pH 4.8. Compressing chitosan with HPMC at different ratios slowed FLZ release, however, time for 80% drug release (T₈₀) did not exceed 4.3?h for the slowest formulation (F11). Adding of chitosan to guar gum at 1:2 ratio (F3) showed delayed release with T₈₀ 17.4?h while, in presence of PVP at 1:2:1 ratio (F5), T₈₀ was 8.8?h. A blend of chitosan and NaCMC at 1:2 ratio (F15) showed prolonged drug release with T₈₀ 11.16?h. Formulations F5 and F15 showed fair physical characteristics for the powder and tablets and were subjected to further studies. Fast swelling was observed for F15 that reached 1160.53?±?13.02% in 4?h with 2?h bioadhesion time to mouse peritoneum membrane compared with 458.83?±?7.09% swelling with bioadhesion time exceeding 24?h for F5. Extensive swelling of F15 could indicate possible dehydration effect on vaginal mucosa. Meanwhile, antifungal activity against C. albicans was significantly high for F5.     

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.     

Oral mucosal bioadhesive tablets of pectin and HPMC: in vitro and in vivo evaluation

The potential of tablets containing 1:4, 1:1 and 4:1 weight ratios of pectin and hydroxypropyl methylcellulose (HPMC) for the sustained release of diltiazem by sublingual administration has been investigated. Measurements of maximum adhesive force to rat peritoneal membrane indicated a satisfactory bioadhesive strength. An in vitro sustained release of diltiazem over 5 h was achieved with bilayer tablets composed of a drug-free ethylcellulose layer in addition to the pectin/HPMC layer containing drug. Plasma concentration-time curves obtained following sublingual administration to rabbits of single and bilayer tablets with 1:1 weight ratios of pectin and HPMC showed evidence of sustained release of diltiazem. Bioavailability of diltiazem was 2.5 times that achieved by oral administration for single layer tablets and 1.8 times for the bilayered tablets.     

复方愈麻美芬缓释片及其释放机理的研究

目的制备复方愈麻美芬缓释片并对释药机理进行研究。方法以HPMC为骨架材料 ,采用湿法制粒 ,制备了复方愈麻美芬缓释片。以释放试验研究了缓释片的释药机理。结果复方愈麻美芬缓释片中盐酸伪麻黄碱和氢溴酸右美沙芬的释药符合一级释放 ,愈创木酚甘油醚的释药符合Higuchi方程。结论采用HPMC为骨架材料 ,结合其他辅料 ,制备复方愈麻美芬缓释片。经释放机理的研究证明其缓释作用。