Design and Evaluation of Lovastatin Solid Dispersions Incorporated Trilayer Matrix Tablets

The current work is aimed to design, prepare and evaluate the trilayer matrix tablets incorporated with lovastatin solid dispersion (SD) for extend drug release. The lovastatin SD prepared by using solvent evaporation technique with varying amounts of polymers (GMS II, Soluplus, Kolliphor ELP, PEG 2000 and Urea) for enhancing the drug solubility. All the formulations examined for physicochemical parameters are within the permissible limits. The optimized SD formulation was incorporated into trilayer matrix tablets which were prepared using different polymers (HPMC 15M & K100M, Chitosan, xanthan gum) by direct compression method for sustaining the drug release. The drug dissolution of optimized lovastatin SD formulation SD15 (drug, soluplus and SLN) was 99.88±5.32% within 60 min which is higher than pure drug 47.33±2.25% and other formulations. The FT-IR, XRD and SEM data assure the compatibility of drug and excipients and amorphous nature of lovastatin. The solid dispersions were further incorporated in to trilayer matrix tablets with active layer and barrier layers. Eight formulations of lovastatin trilayer matrix tablets (AF9-HF9) designed and checked for pre compression parameters. Formulation GF9 demonstrated highest drug release of 99.41±5.28% for 24 hours sustainably over an extended period of time and excellent flow properties. The release order kinetics data indicate the zero order release with highest R2 of 0.9957 for GF9, superior than market extended release formulation (R2=0.9934). All the formulations showed best fit to Higuchi model and Korsmeyer-Peppa’s model indicating diffusion and non-Fickian diffusion process of drug release. GF90 was found to be stable for 180 days at accelerated conditions. Hence the solubility, dissolution rate of lovastatin was enhanced by SD technique further incorporated in to trilayer matrix tablets for sustainable extended drug release upto 24 h.

Formulation And Characterization Of Ondansetron Hydrochloride Matrix Tablets For Sustained Drug Delivery

The objective of proposed work was to develop Ondansetron Hydrochloride (OND HCl) sustained release matrix tablets for the better treatment of vomiting for extended period of time. Sustained release matrix tablet is the drug delivery system that is designed to achieve a prolonged therapeutic effect by continuously releasing medication over an extended period of time after administration of single dose. The matrix tablets of OND HCl were prepared by direct compression method using varying ratio of hydroxy propyl methyl cellulose (HPMC) and ethyl cellulose. The bends of tablets were evaluated for bulk and tapped density, % compressibility index and angle of repose and powder of all formulations blend exhibited that low interparticle friction and excellent flow characteristics. The prepared matrix tablets were then assessed for different physical tests like consistency of weight, thickness, hardness, friability, drug content and in vitro drug release. Each batch of the OND HCl matrix tablets were of good quality as to hardness, thickness, friability and % medicament content. The in vitro drug release study was done for 2 hours by utilizing paddle technique in 0.1N HCl (pH 1.2) as dissolution media and 6 hours using phosphate buffer (pH 6.8) as dissolution media. The drug release study showed that all formulation FMT-1, FMT-2, FMT-3, FMT-4, FMT-5 and FMT-6 were provide the drug release on sustained manner up to 8 hrs. Amongst the developed matrix tablets formulations, FMT-2 containing ethyl cellulose (100 mg) was optimized as best because FMT-2 show highest drug release profile and promoting the sustained release of drug, which could potentially improve the patient compliance.

Formulation Design And Optimization Of Floating Matrix Tablets Of Ciprofloxacin Hcl By Using Hpmc And Ethyl Cellulose With Experimental Design

The oral floating matrix tablets of Ciprofloxacin Hydrochloride were formulated by Experimental design by using HPMC K100M and Ethyl Cellulose as the retardant polymers each with three different levels with an approach to increase gastric residence and thereby improve drug bioavailability. From FTIR results it was confirmed that there is no chemical interaction between the drug with the excipients used in tablet formulations. Also, there was no shift in the endotherm of in the drug- excipients mixtures indicating compatibility of drug with all the excipients. All the tablets were prepared by effervescent approach in which Sodium bicarbonate was added as a gas generating agent. Floating Matrix tablets were prepared by direct compression method and prepared tablets were evaluated for weight variation, percentage friability, hardness and drug content studies. All the formulations showed compliance with pharmacopeia standards (I.P. 1996). Floating lag times of all the formulations were within 1 minute and Total floating time of all the formulations were more than 12 hours. In vitro release studies revealed that the release rate decreased with increase polymer proportion of retarding polymers. The formulation CHE9 sustained release of drug for 12 hours with 21% release of drug after 1 hour and more than 97% at the end of 12 hours. From the Kinetic model it was found that the optimized formulation CHE9 showed linearity in case of Zero order (R2: 0.938) and Higuchi model (R2: 0.954). By fitting data to Korsmeyer-Peppas model and ‘n’ value lying above 0.5 indicating non Fickian release.

Preparation and in vitro & in vivo evaluation of cephalexin matrix tablets

The purpose of the study is to develop cephalexin controlled-release matrix tablets by using lower proportions of release retardant polymer and to establish their in vitro & in vivo correlation. Tablets were compressed by incorporating polymers in a matrix form along with drug which prolong the drug release. Twelve formulations were prepared by mixing ethyl cellulose (EC) and hydroxypropyl methylcellulose (HPMC) (three different viscosity grades) in various proportions. F-1 to F-4 formulations were prepared by incorporating drug, HPMC K4M and ethyl cellulose in 100 : 5 : 5, 100 : 10 : 5, 100 : 15 : 5 and 100 : 20 : 5; similarly, F-5 to F-8 were prepared with HPMC K15M; and F-9 to F-12 were prepared with HPMC K100M using a wet granulation process maintained same proportions, along with drug and EC. Tablets were evaluated for their pre-compression and post-compression characteristics and they were found to be in limits. From the dissolution testing, F-4 showed 100.34% medicament release in 12 h. In vivo studies were conducted on rabbit and pharmacokinetic parameters of the optimized formulation were evaluated using HPLC method. It was found that matrix tablets showed increased t1/2 and decreased Kel. The design signified that the drug release rate from tablets was influenced by the small proportion (around 7% of a tablet weight) of polymer mixture and it controlled 100% medicament release upto 12 h effectively with the low grade viscosity of HPMC combination, with good in vitro & in vivo correlation.

Application of Mixture Uniform Design in Optimizing the Proportion and Releasing Mechanism Study of GA and GB Hydrophilic Gel Matrix Tablets / 中国中医药信息杂志

Objective To optimize the prescription of GA and GB hydrophilic gel matrix tablets; To study the in vitro release mechanism. Methods On the basis of the results of the mono-factor investigation, mixture uniform design was used to optimize the handicraft molding prescription of GA and GB hydrophilic gel matrix tablets. The release mechanism was investigated by the vitro of the GA and GB hydrophilic gelmatrix tablets to accumulate releasing rate to conduct linear fitting. Results The optimized prescription of GA and GB hydrophilic gel matrix tablets was: powder: HPMC: lactose=23:24:53. Conclusion Mixture uniform design can be used to optimize the prescriptions of GA and GB hydrophilic gel matrix tablets, and the results are accurate. The hydrophilic gelmatrix tablets release medicine by non-Fick mechanism, and the medicine release is in accordance with zero-order.

Advances of wax matrix tablets / 中国药科大学学报

@#Wax matrix tablets is a special pharmaceutical controlled release preparation. However, it has not yet been fully studied and applied. In this article, the progress in carriers and techniques for the preparation of wax matrix tablets in recent years was reviewed. Analysis and comparison of their advantages and disadvantages can help to promote the application of wax matrix tablets in the future.

A Five-Year Stability Study of Controlled-Release Diltiazem Hydrochloride Tablets Based on Poly(Ethylene Oxide).

The aim of this study is to investigative the stability of poly(ethylene oxide) (PEO) matrix tablets containing diltiazem hydrochloride (DTZ) after five-year storage at room temperature. DTZ matrix tablets containing different molecular weights (MW) of PEO and electrolytes (sodium carbonate anhydrous Na2CO3, potassium chloride KCl and pentasodium tripolyphosphate anhydrous PSTPP) were prepared. The fresh and stored tablets were evaluated by DTZ content, in vitro drug release rates and kinetics as well as DSC. All the PEO’s matrix tablets showed no significant changes in release rate, kinetics and drug content. The release rates of DTZ following five-year storage were slightly increased as the MW of PEO increased from 900,000 to 8,000,000. Also, it was clear that the addition of electrolyte drastically slowed the release rates of DTZ from fresh and stored tablets. DSC thermograms and similarity factor (ƒ2) depicted good system stability for all stored tablets. This is the first five-year long-term stability study reported concerning DTZ/PEO matrix tablets with different MW, which proved its stability for several years. This study might throw light on the dramatic difference observed between this study and the reported data of accelerated stability testing under stress conditions found in the literature.

Fabrication of Bucco-matrix tablets of Amoxicillin trihydrate on the basis of release and permeation kinetics.

Drug release kinetics from matrix dosage form is governed by polymer swelling and erosion, drug dissolution/diffusion and polymeric combination. For the preparation of controlled release dosage form, hydrophilic, swellable polymers in optimum combination are essential. The major objective of the current study is to prepare Amoxicillin trihydrate-loaded bucco-matrix tablets by direct compression technique and to study the effect of ratio of HPMCK100M and HPMCK15M used in the formulation on the basic properties and on drugrelease and permeation kinetics. The tablets offered satisfactory physicochemical results. The buccal strength, detachment force and bond strength of the tablets were good enough to hold the tablets in the buccal region. The drug release data generated during in vitro drug release study of bucco-matrix tablets in phosphate buffer pH 6.8 were evaluated by zero-order, first-order, Higuchi, Korsmeyer – Peppas, and Kopcha models. Release exponent (n) of Korsmeyer- Peppas equation of the formulations exhibited diffusion as the principal mechanism of drug release. It was further confirmed by Kopcha model. Evaluation of diffusion and erosion terms in the Kopcha model showed that diffusion dominated swelling or erosion process through out the study. The permeation kinetics of the drug showed linearity when studied across goat buccal mucosa. Permeation coefficient of drug decreased with increase in % swelling index of the formulations.

Optimization of the Formula of Konjac Glucomannan-Paeonol Matrix Tablets / 医药导报

Objective To optimize the formula of konjac glucomannan-paeonol matrix tablets. Methods The formula of paeonol matrix tablets was optimized by the orthogonal design with the accumulative release rate in vitro as index, with the viscosity of konjac glucomannan ( KGM) , the amount of KGM and lactose as influence factors. Results The optimized formula was as follows:the viscosity of konjac glucomannan was 20 000 mPa·s, KGM 30%, lactose 20% and the release in vitro fit into the Higuchi equation. Conclusion The formula of the paeonol matrix tablets is reasonable and the tablets have well release effect in vitro.

Formulation and in-vitro bioequivalence evaluation of verapamil hydrochloride matrix tablets with Calan SR.

The purpose of the current work was to formulate Verapamil Hydrochloride (VH) sustained release matrix tablets by using natural polymers and comparison with leading national brand Calan SR of Searle Pharmaceuticals. Tragacanth and pectin were used in various concentrations. Pre compression studies i.e. angle of repose, bulk density, tapped density, Carr’s compressibility index and Hausner’s ratio were also performed and found within the Pharmacopoeial limits. Eight formulations (F1-F8) of (VH) were prepared by direct compression method. Post compression studies i.e. Thickness, Hardness, Diameter, Friability and Dissolution studies were conducted. Different kinetic models i.e. zero order, first order, Highuchi model and Korsmeyer Peppas were applied to study release patterns and similarity index was calculated. Dissolution studies were carried out in phosphate buffer of pH 6.8 showed that formulations (F4 and F8) formulated with higher polymers concentration showed comparatively better drug retardation. F5 was the most comparable with the reference product. Verapamil hydrochloride released was observed non-fickian as diffusion following Higuchi model.

Fabrication and Optimization of Novel Lornoxicam Matrix Tablets Using 3-Factor 3-Level Box-Behnken Statistical Design: Invitro and Invivo Evaluation.

In the present study efforts have been made to prepare sustained release matrix tablets of Lornoxicam. Matrix tablets were prepared by direct compression method by using Hydroxypropyl methyl cellulose K15 (HPMC- K15), Ethyl cellulose (EC) and Sodium carboxy methyl cellulose (Na-CMC) as polymers in different concentrations. A 3-factor 3- level Box-Behnken statistical design was used as an optimization tool having total of 17 experimental runs with 5 central points. All three polymers were selected as independent variables while %age drug release at various time intervals and hardness were used as dependant variables. In vivo studies were conducted on human plasma using Tenoxicam as internal standered. All the detections were made on SYKNM HPLC. Foriour Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetery (DSC) studies were conducted and no chemical interaction was found between drug and polymers. The drug release mechanism was mainly governed by non-fickian (anomalous) diffusion and zero-order (case II) transport diffusion. Regression analysis was performed on dissolution data obtained with the selected response variables and polynomial models were constructed. Polynomial models were further validated using one way ANOVA and results indicated that all the polymers used have significant effect on selected response (p>0.05). Contour plots and three dimensional response surface curves were drawn. In- vivo studies were conducted on two tablet formulation indicating slow and sustained release of the drug from matrix. From Behnken design it is possible to successfully formulate and optimize Lornoxicam sustained release matrix tablets with three polymers (HPMC- K15, EC and Na-CMC) in combination.

Implementation of time release technology in formulation development and evaluation of sustained release tablet of Lornoxicam.

In present study, the attempts have been made to formulate sustained release tablets of lornoxicam by direct compression method. Based on viscosity grades different proportions of hydrophilic polymers (HPMC K4M, HPMC K15M, HPMC K100M) are used for preparation of lornoxicam sustained release matrix tablet. The drug excipient mixtures were subjected to preformulation studies comprising of micromeritic properties. The tablets were subjected to various studies like as physicochemical studies, in vitro drug release, kinetic studies, etc. FTIR studies shown there was no interaction between drug and polymers. The physicochemical properties of tablets were found within the limits. Lornoxicam is a first generation analgesic, inflammatory & antipyretic agent used in relieving symptoms of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute sciatica and low back pain. From developed formulations batch F1 have shown zero order drug release behavior and prolong drug release over a period of 12 h which was deemed as suitable and optimum formulation for sustained drug delivery. Results of the present study indicated the suitability of the low viscous polymer in the proportion of (drug:polymer) 1:1 in the preparation of sustained release formulation of lornoxicam.

Formulation and in-vitro bioequivalence evaluation of verapamil hydrochloride matrix tablets with Calan R.

The purpose of the current work was to formulate Verapamil Hydrochloride (VH) sustained release matrix tablets by using natural polymers and comparison with leading national brand Calan SR of Searle Pharmaceuticals. Tragacanth and pectin were used in various concentrations. Pre compression studies i.e. angle of repose, bulk density, tapped density, Carr’s compressibility index and Hausner’s ratio were also performed and found within the Pharmacopoeial limits. Eight formulations (F1-F8) of (VH) were prepared by direct compression method. Post compression studies i.e. Thickness, Hardness, Diameter, Friability and Dissolution studies were conducted. Different kinetic models i.e. zero order, first order, Highuchi model and Korsmeyer Peppas were applied to study release patterns and similarity index was calculated. Dissolution studies were carried out in phosphate buffer of pH 6.8 showed that formulations (F4 and F8) formulated with higher polymers concentration showed comparatively better drug retardation. F5 was the most comparable with the reference product. Verapamil hydrochloride released was observed non-fickian as diffusion following Higuchi model.

A sustained release of tablet granules associated with ZnS nanocrystals using Tamarind seed polysaccharide.

Tamarind seed polysaccharide (TSP) isolated from tamarind kernel powder was investigated for sustained release manners of salicylic acid drug. Tablet granules of salicylic acid were prepared, with two different grades of TSP and Cross linked TSP and embedded with chemically synthesized ZnS nanocrystals. Five different formulations made and the drug excipient mixtures were subjected to pre-formulation studies such as physicochemical studies, in vitro dissolution test, disintegration test, angle of repose and drug content. The physicochemical properties of tablets were found within the limits. Formulation F1 and F5 containing TSP and Cross linked were found to release the drug in sustained manner up to 24 hour and were stable under accelerated conditions of temperature for 6 months since there were no significant changes in drug content and physical parameters. This formulation was more comfortable to the user due to less erosion, faster and optimum pH of surrounding medium.

Effect of excipients on oxcarbazepine release from modified release matrix tablets.

The present investigation was undertaken with an objective of formulating modified release (MR) matrix tablets of Oxcarbazepine (OXC) an anti-epileptic drug, based on cellulose ether polymers like Hydroxy Propyl Methyl Cellulose (HPMC K4M and LVCR 100) and Hydroxy Propyl Cellulose (HPC JF) as drug release retardants to overcome poor patient compliance and exposure to high doses associated with currently marketed immediate release (IR) dosage forms. The tablets were prepared by direct compression process and evaluated for various physico- chemical/mechanical parameters. Among three polymers used, HPMC LVCR 100 is selected as release retardant based on the viscosity and gel formation during dissolution. The effect of different fillers like Avicel PH 101, Avicel PH 105, Pre gelatinized starch (PGS), maize starch with spray dried lactose (FLOWLAC) and Di-calcium phosphate (DCP) on OXC release was also studied and the OXC percent release at the end of 12h is in the order of DCP>FLOWLAC>Avicel PH 101>Avicel PH 105>PGS. Based on the dissolution data obtained with different fillers and keeping in view of the results from the pre compression studies, and gel layer retaining with the matrix tablets, Avicel PH 105 was selected as carrier to carry out further formulation development. Since, OXC is poorly water soluble drug, solubilizing agents like surfactants, cyclodextrins and polyethylene glycols were included in the formulations and their effect on OXC release was studied in order to achieve therapeutic effective levels. Formulations containing 20% (w/w) of Hydroxy Propyl-β-Cyclodextrin gave superior OXC release of 85.50 ± 1.62% at the end of 12hours and fulfils the regulatory requirement. The dissolution data was also evaluated for drug release kinetics and mechanisms.

Formulation and evaluation of sustained releasematrix tablets of glimepiride based on combinationof hydrophilic and hydrophobic polymers.

The objective of this study was to develop sustained release tablets of glimepiride by wet granulation method based on combination of hydrophilic (HPMC15cps, HPC) and hydrophobic (Ethyl cellulose) polymers. The drug excipient mixtures were subjected to preformulation studies. The tablets were subjected to physicochemical studies, in- vitro drug release, kinetic studies and stability studies. FTIR and DSC studies shown there was no interaction between drug and polymers. The physicochemical properties of tablets were found within the limits. Glimepiride is a first third generation sulphonyl urea agent for the treatment type II diabetes mellitus. The drug release from the optimized formulation was extended for a period of 12 hrs. The kinetic treatment showed that the release of drug follows first order models. The optimized formulations were subjected to stability studies and shown there were no significant changes in drug content, physicochemical parameters and release pattern. Results of the present study indicated the suitability of the above mentioned polymers in the preparation of sustained release formulation of glimepiride.

Design and evaluation of sustained release matrix tablets of glimepiride based on combination of natural and synthetic polymers.

The present research work was aimed to develop matrix tablets of Glimepiride with Aloe barbadensis miller leaves mucilage and Povidone and to study its functionality as a matrix forming agent for sustained release tablet formulations. Physicochemical properties of dried powdered mucilage of Aloe barbadensis miller mucilage and Povidone tablet blend were studied. Various formulations of Glimepiride Aloe barbadensis miller mucilage and Povidone were prepared. They found to have better satisfactory physicochemical properties with low SD values. The swelling behavior and release rate characteristics were studied. The dissolution study proved that the dried Aloe barbadensis miller mucilage and Povidone combination can be used as a matrix forming material for making Sustained release matrix tablets.

Preparation of sinomenine hydrochloride?-carrageenan/konjac glucomannan matrix tablets and study on its in vitro release mechanism / 中草药

Objective To study the formulation and preparation factors influencing in vitro release mechanism of drug from?-carrageenan/konjac glucomannan hydrophilic matrix tablets.Methods The matrix tablets containing sinomenine hydrochloride as a model drug were obtained by direct compression method or wet granulation technique.The effects of the ratios of?-carrageenan/konjac glucomannan,the amount of matrix materials,the kinds of diluent agent,tablet size,preparation method,and compressing pressure on release mechanism of the matrix tablets were studied by evaluating the n value in the Peppas equation. Results The release mechanism of the matrix tablets was non-Fickian release that coupled diffusion and erosion modle.With a decrease in the ratio of?-carrageenan/konjac glucomannan,a decrease in the amount of matrix materials,a decrease in the water-solubility of diluent agents,an increase in tablet size,and a decrease in compressing pressure,the ratio of drug diffusion was increased.Preparation method had little influence on drug release mechanism.Conclusion Drug could be slowly released from the matrix tablets containing?-carrageenan/konjac glucomannan as matrix material,the main factors influencing drug release mechanism are the ratio of?-carrageenan/konjac glucomannan,the amount of matrix materials, the kinds of diluent agent,tablet size,and compressing pressure.