Extended Release Matrix Tablets Research Articles

Exploring the potential of neem and tamarind gum as release retardants: Design and statistical optimisation of vildagliptin extended release matrix systems using D-optimal quadratic mixture design

Exploring the significant role of natural polymers in developing drug delivery systems has been a promising area of research interest. The current investigation uses a D-optimal quadratic mixture design to design and evaluate neem and tamarind gum-based vildagliptin extended-release matrix tablets. Studying the combination effect of gums is one of the major objectives. Initial screening studies were performed to select the factors and their levels. The variables selected at different levels in mg/tablet are neem gum, tamarind gum, polyvinylpyrrolidone, and lactose monohydrate. Based on the screening experiments with both gums, the polymer content of 165 mg was chosen as the highest level in the DOE. Nineteen runs were generated to screen the desired parameters as responses. The total weight of the formulation was kept constant at 275 mg. Time (hours) required for 50 %, 90 % and 100 % of drug release and tablet hardness were selected as the responses for each run. The wet granulation method was adopted, and the critical variables were optimised using the design of experiments following Design Expert software. Statistical analysis was conducted, and the optimised formulations were prepared and evaluated to compare with the predicted responses. Stability studies were performed for the optimised batches. Results indicated that the prepared batches met the compendial limits and confirmed the application of neem and tamarind gum in the development of extended-release tablets of vildagliptin for 24 h. An optimised formulation comprising of 16.52 mg of neem gum and 148.48 mg of tamarind gum with a hardness of 7.5–8.5 kp produced 50 %, 90 % and 100 % drug release in 12, 22 and 25 h.

Characterization of Channeling Effects Applied to Extended-Release Matrix Tablets Containing Pirfenidone.

Pirfenidone (PRF) is an anti-fibrotic agent that has been approved by the Food and Drug Administration (FDA) for the treatment of mild to moderate idiopathic pulmonary fibrosis. However, the current oral administration dosing regimen of PRF is complex and requires high doses. Patients are instructed to take PRF three times daily, with each dose consisting of up to three capsules or tablets (600 mg/d or 1.8 g/d of PRF) taken with food. To improve the dosing regimen, efforts are being made to develop an extended-release tablet with a zero-order release pattern. In this study, two types of extended-release matrix tablets were compared: non-channeled extended-release matrix tablets (NChMT) and channeled extended-release matrix tablets (ChMT). In vitro release tests, swelling and erosion index, rheology studies, and X-ray microcomputed tomography (XRCT), were conducted. The results indicated that ChMT maintained a zero-order release pattern with a constant release rate, while NChMT exhibited a decreased release rate in the latter half of the dissolution. ChMT exhibited accelerated swelling and erosion compared to other formulations, and this was made possible by the presence of channels within the tablet. These channels allowed for thorough wetting and swelling throughout the entire depth of the tablet. The formation of channels was confirmed through XRCT images. In conclusion, the presence of channels in ChMT tablets increased the rate of swelling and erosion, resulting in a zero-order release pattern. This development offers the potential to improve the dosage of PRF and reduce its associated side effects.

Formulation and evaluation of extended-release tablets of trimetazidine HCL

The present study was undertaken with an aim to formulate develop and evaluate Trimetazidine HCL extended release matrix tablets using different polymers as release retarding agent. Pre formulation study was done initially and results directed for the further course of formulation. Based on Pre formulation studies different batches of Trimetazidine HCL were prepared using selected excipients. Powders were evaluated for tests Angle of repose, Bulk density, tapped density, compressibility index, and Hausner ratio before being punched as tablets. It was concluded that the tablets of batch F9 had considerable swelling behaviors and in vitro drug release. Percentage drug release in 8 hr is 80.77. It was observed that tablets of batch F9 followed the Huguchi release profiles. From the results and discussion it is concluded that formulation of Extended release matrix tablet of HCL containing HPMC K-15 (19.44%) and Hyper mellose (19.44%), Ethyl cellulose (19.44%) batch F9 can be taken as an ideal or optimized formulation Extended release matrix tablet for 8 hour release as it fulfills the requirements for extended release matrix tablet.

Formulation Development and In vitro Characterisation of Stavudine Extended Release Matrix Tablets

The aim of the present study was to develop Stavudine extended release tablets to maintain constant therapeutic levels of the drug for over 12 hrs. Xanthan gum, Sodium CMC and HPMC 15cps were used as polymers. All the formulations were passed various physicochemical evaluation parameters such as Bulk Density, Tapped Density, Carr’s Index, Hausners Ratio, Angle of Repose, Weight Variation, Hardness, Thickness, Friability and Drug Content. From the dissolution studies it was evident that the formulation F6 showed better and desired drug release pattern i.e., 99.12% in 12 hours. It contains the Sodium CMC as polymer. It followed Kars Mayer peppas release kinetics mechanism.

Design and Evaluation of Extended-Release Matrix Tablet of Tramadol Hydrochloride

The impartial concerning this study was to cultivate extended-release matrix pellet of Tramadol hydrochloride using various combinations of hydrophilic polymers (HPMC, Carbopol, Xanthum Gum). The form tablets were prepared by direct compression method. The pre and post compression description of blend and tablet were judged. The in-vitro dissolution studies revealed that the blend of HPMC and Carbopol in different aggregation showed hinder release of 63% at the end of 12th hour and in addition to 94.24% at the end of 24th moment, thereby appearance good release pattern necessary for ER tablet and shown good kinetic release connected of diffusion and deterioration. Hence hydrophilic polymer HPMC and Carbopol was found to extended release of very water-soluble drug, Tramadol hydrochloride.

Formulation and In Vivo Evaluation of Pharmacokinetics Parameters of Extended Release Matrix Tablet Containing Drug Benidipine Hydrochloride by Using PK Solver Software

In this experimental work an extended release matrix tablet of Benidipine Hydrochloride (BH) has been prepared to extend drug release for more than 18 hr which has advantage of continuous 24 hr control of blood pressure (BP) in hypertension patient, showing long-lasting pharmacological activity and increases the patient compliance. Benidipine is a calcium channel blocker that is used for the treatment of mild to moderate hypertension and angina pectoris and BH extended release tablets reduce the side effects associated with multiple dosing used during conventional tablets. Tablets are prepared tablets containing different polymers concentration through direct compression method. The in vitro percentage drug release and drug release mechanism were studied. From the drug release mechanism, the tablets showed the Higuchi square root model and R2 values for batch F2 (R2 =0.998) indicates that the drug released by diffusion mechanism and from Peppas equation n value 0.720 (range 0.89-1) indicates that diffusion–erosion mechanisms resulting from swelling and hydration behavior of Chitosan and along with HPMC K 100 M and Eudragit R S 100 extending drug release. Different pharmacokinetics parameters has been studied from results of in vivo study by using PK solver software which shows that marketed conventional BH tablet reached peak plasma concentration of 830.986 µg/ml after 2 hr of administration, where as selected optimized prepared tablets reached the maximum concentration of 708.83 µg/ml after 1 hr of administration, but it continues to release drug for more than 36 hr when in vivo was carried out in carried out on white New Zealand rabbits. These results proved that drug is released slowly for prolonged period of time and achieving better BP control. So based on this research outcome and results, we may conclude our objective is achieve by extending drug release pattern of BH.

Development of an In Vitro Drug Release Method to Enable In Vitro-In Vivo Correlation of Potassium Chloride Extended-Release Tablets.

An in vitro drug release test was developed to establish a level A in vitro-in vivo correlation (IVIVC) for predicting the in vivo performance of potassium chloride extended-release (ER) matrix tablets. Three ER formulations of potassium chloride with different in vitro release rates were designed using the USP dissolution test, and their urinary pharmacokinetic profiles were evaluated in healthy subjects. Due to the lack of IVIVC with the USP method, experiments were designed to investigate the effects of in vitro test conditions on drug release in order to match in vitro drug release with in vivo behaviors of different formulations. The evaluated in vitro variables included the type of USP apparatus, surfactant, and ionic strength of the dissolution medium. Based on the study findings and data analysis, a discriminatory drug release method was successfully developed that enabled the establishment and validation of a level A IVIVC model of the potassium chloride ER tablet using urinary pharmacokinetic data. This method uses USP apparatus I at 50 rpm in 900 mL of 150 mM NaCl solution containing 40 mM sodium dodecyl sulfate at 37 °C. The current study highlights the value of investigating test conditions in developing a predictive in vitro test method for establishing IVIVC.

Convolution- and Deconvolution-Based Approaches for Prediction of Pharmacokinetic Parameters of Diltiazem Extended-Release Products in Flow-Through Cell Dissolution Tester

The present study evaluated the effect of different configuration setups of the Flow-Through Cell (USP IV) dissolution tester in developing in vitro–in vivo correlation (IVIVC). A Biopharmaceutics Classification System (BCS) Class I Diltiazem (DTZ), formulated in extended-release (ER) gel-matrix system, was employed for this purpose. The study also assessed the validity and predictability of IVIVC employing both deconvolution- and convolution-based approaches. In vitro release was conducted in USP IV as open- or closed-loop setups, while the pharmacokinetic (PK) data were obtained from a previous fasted-state cross-over study conducted on 8 healthy male volunteers, after oral administration of ER matrix tablets against market product (Tildiem Retard® 90 mg). PK parameters (Cmax, AUC0-t and AUC0-∞) were predicted, and compared with actual data to establish the strength of correlation models. Results showed that DTZ release from ER products was influenced by operating the FTC in different configuration-setups, where ≥ 75% of labeled DTZ was released after 6 h and 12 h using the open- and closed-loop settings, respectively. Correlation between fraction-dissolved versus fraction-absorbed for both ER products displayed linear relation upon employing FTC open-loop setup. Convolution-based approach was more discriminative in predicting DTZ in vivo PK parameters with a minimal prediction error, compared to deconvolution-based approach. A successful trial to predict DTZ PKs from individual in vitro data performed in USP IV dissolution model was established, employing convolution technique. Basic principle of the convolution approach provides a simple and practical method for developing IVIVC, hence could be utilized for other BCS Class I extended-release drug products.Graphical abstract

Formulation design and Evaluation of Extended-Release Tablets of Oxybutynin for Effective Management of Overactive Bladder Syndrome

Overactive bladder syndrome (OAB) is a chronic condition with a composite of symptoms and has a significant negative impact on the physiological and psychological well-being of the patients. The present study is aimed at developing extended-release formulations of oxybutynin that is effective in reducing the side effects associated with the drug by maintaining a steady state concentration with minimal fluctuations in plasma drug concentration and thereby achieves improved patient compliance. The extended-release drug delivery of tablets can be achieved by preparing the matrix tablet of oxybutynin chloride with klucel HF in core tablet by wet granulation technique and functional coating with a combination of aquacoat ECD-30 and hypromellose E5 followed by film coating with opadry. For confirmation of compatibility, the pure drug and its physical mixtures were subjected to FTIR studies. All the formulations have shown acceptable limits in all precompression and post compression parameters. The in vitro release studies in 0.1N HCl and 6.8 phosphate buffer revealed that the optimized formulation F10 extend the release of the drug to 91% at 24 hours and the release profile was similar to the innovator’s product as revealed by the similarity factor study. The release kinetics study revealed that the release of the drug followed diffusion mechanism. Stability studies of the selected formulation tablets were carried out at 25°C ±2°C/60% RH±5% and 40°C ±2°C /75%±5% RH for different time period and all the parameter was within the limits after storage period. Thus the extended release matrix tablets of oxybutynin chloride developed in this study have immense potential to develop into a marketed product following the testing in animals and human volunteers.

3D-Printed Coating of Extended-Release Matrix Tablets: Effective Tool for Prevention of Alcohol-Induced Dose Dumping Effect

Tablets used for extended drug release commonly contain large amounts of drugs. The corresponding drug release mechanism thus has to be well-known and invariable under numerous conditions in order to prevent any uncontrolled drug release. Particularly important is the stability and invariability of the release mechanism in the presence of alcohol due to the possible occurrence of the dose dumping effect. The effect of 3D printing (3DP) coating on the drug release mechanism and the drug release rate was studied as a possible tool for the prevention of the alcohol-induced dose dumping effect. Three types of matrix tablets (hydrophilic, lipophilic, and hydrophilic-lipophilic) were prepared by the direct compression method and coated using 3DP. The commercial filament of polyvinyl alcohol (PVA) and the filament prepared from hypromellose by hot melt extrusion (HME) were used as coating materials. Both coating materials were characterized by SEM, DSC, Raman spectroscopy, and PXRD during particular stages of the processing/coating procedure. The dissolution behavior of the uncoated and coated tablets was studied in the strongly acidic (pH 1.2) and alcoholic (40% of ethanol) dissolution media. The dissolution tests in the alcoholic medium showed that the Affinisol coating was effective in preventing the dose dumping incidence. The dissolution tests in the acidic dissolution media showed that the Affinisol coating can also be useful for the delayed release of active substances.

SUSTAINED RELEASE MATRIX DRUG DELIVERY SYSTEM: AN OVERVIEW

Oral delivery of drugs is the most preferable route of drug delivery due to the ease of administration, patient compliance and flexibility in formulation, etc. Sustained release constitutes are the dosage form that provides medication over an extended time or denotes that the system is able to provide some actual therapeutic control whether this is of a temporal nature, spatial nature or both. The objective of the study was to explore the necessity, advantages and various techniques of extended release matrix tablet to get a constant drug delivery rate and reproducible kinetics for advance delivery. Matrix tablets are the type of controlled drug delivery systems, which release the drug in continuous manner by dissolution controlled as well as diffusion controlled mechanisms. To control the release of the drugs, which are having different solubility properties, the drug is dispersed in swellable hydrophilic substances, an insoluble matrix of rigid non swellable hydrophobic materials or plastic materials. Matrix tablets can be formulated by either direct compression or wet granulation method by using a variety of hydrophilic or hydrophobic polymers. The extended release matrix tablets can assure better patient compliance through reduction in total dose and dosage regimen, which can be great help to treat chronic diseases. This review highlights the types of matrices, mechanisms involved and evaluation studies.

POROUS PLASTIC MATRIX TABLETS OF LEVETIRACETAM FOR ZERO-ORDER CONTROLLED RELEASE: DEVELOPMENT AND FORMULATION OPTIMIZATION

Objective: The prior objective of the current research work was to develop once-daily levetiracetam extended/controlled-release tablets having zero-order release kinetics with the plastic matrix as the release retarding element. For a high water-soluble drug, the formulation of a dosage form so as to have an extended drug release has always been a difficult task.
 Methods: In the current work, levetiracetam which is a highly soluble drug was taken as the model drug for which extended-release matrix tablets were developed using varied plastic polymers like Polyvinyl acetate (PVAc), Polyvinyl chloride (PVC), Eudragit RSPO and Eudragit RLPO. PVP was considered as a pore-forming agent and PEG 6000 was taken as a water regulating agent. The porous plastic matrix tablets were prepared by embedding the drug in solvent-activated polymer dispersion followed by drying, sieving, mixing with other excipients and finally compressed. Including physical characterization studies and drug release studies, the tablets were subjected to SEM studies before and after the dissolution studies to analyze the effect of the pore former.
 Results: Pre-compression mixtures exhibited good packageability of 81-92% and hence the compressed tablets were strong enough with good tensile strength in the range of 0.78–0.90 N/mm2. Drug release study results showed that the drug release was controlled for a period of 12–24h. PVAc had shown better controlled-release among all the plastic polymers taken. PEG 6000 in combination with PVP produced the desired zero-order drug release.
 Conclusion: The levetiracetam porous plastic matrix tablets were developed with zero-order drug release that was effectively controlled for 24hr.

A REVIEW ON CONTROLLED RELEASE MATRIX TABLET

Oral route is the most convenient route of drug administration. So far so many oral dosage forms have been developed to improve the patient compliance. The drugs with less half life are eliminated from the body with in short period of time. Different types of extended release matrix tablet have been explained briefly along with the various formulation which mainly by wet granulation or direct compression method or by dispersion of solid particle within a porous matrix formed by using different polymers. This review highlights the types of matrices, mechanisms involved and evaluation studies.
 Keywords: Controlled release, matrix tablet, Polymer, Diffusion

Polyglycerol esters of fatty acids as safe and stable matrix forming tableting excipients: A structure-function analysis

This work describes a novel approach for the development of extended release matrix tablets with stable performance via direct compaction. Selected molecules belong to polyglycerol esters of fatty acids (PGFAs) - a group of lipid-based excipients (LBE) with advanced solid-state stability - were used for developing extended release tablets. Metformin HCl as a freely water soluble API was used as model substance. Three PGFA compounds with a HLB range of 1.8–4.5 were selected as matrix forming agents. The deformation behavior of tableting blends with and without PGFAs and their flow properties studied. Blends composing PGFAs showed reduced yield pressure and decreased internal friction between particles, suggesting the tendency to plastic behavior of PGFAs and improved flow properties of their blends, respectively. The blends of selected lipids with API and filler were directly processable via direct compression without any pretreatment such as granulation. The resulted tablets showed desired tensile strength and friability. Application of PGFAs with different HLB allowed the tailoring of API release profile for different time periods with the same concentration of lipid in the tablet. The stable release profile was related to the stable solid state of lipids as matrix agent. No in vitro cytotoxic effect was observed by assessing the dehydrogenase activity.

Formulation and Evaluation of Extended Release Matrix Tablets of Tenatoprazole Sodium using Synthetic Polymers

Extended release formulations are designed to release their medication in a controlled manner at a predetermined rate, duration and location to achieve and maintain optimum therapeutic blood levels of a drug. The present investigation is aimed to formulate the extended release matrix tablets of Tenatoprazole sodium with various grades of different polymers like Carbopol, HPMC and Eudragit grades. The tablets were prepared by wet granulation technique. The prepared ER Matrix tablets were evaluated for various physico chemical parameters. All the formulations resulted in acceptable Pharmacopoeia limits. In-vitro drug release studies (USP dissolution rate test apparatus II, 75 rpm, 37°C ±0.5°C) using 0.1N hydrochloric acid (1.2 PH ) for first 2 hrs and phosphate buffer (PH 6.8) as a dissolution medium (900ml) for the next 12 hrs. Among all the formulation F-5(drug: Carbopol-974P-NF in ratio of 1:1.5) shows better result upto 12 hours of the drug release was found to be 99.47±0.22 so it’s an Optimized formulation. Key words: Carbopol, ER Matrix, Eudragit, Methocel, Tenatoprazole sodium, Wet granulation.

Formulation development and characterization of cellulose/ polyacrylic acid – based polymers on the release of celecoxib from extended release tablets

The study was aimed to formulate an extended release matrix tablets of celecoxib and to investigate the influence of different types and concentration of polymers on release of drug. Six formulations namely F1 – F6 were manually designed using different proportions of polymers. The matrix tablets formulations (F1 – F5) were composed of using different polymers such as, hydroxypropyl methylcellulose (HPMC-K4M), carboxymethyl cellulose (CMC), ethylcellulose (EC-10 cps) and Carbopol-940, whereas plain tablets formulation (F6) without polymer contained microcrystalline cellulose (MCC), lactose monohydrate, sodium lauryl sulfate (SLS) and polyvinylpyrrolidone (PVP-K30). The MCC, SLS and PVP-K30 were used in a fixed quantity in all formulations except F6 i.e. 20.7%, 6.7%, and 2%, respectively. Multiple point dissolution was performed in phosphate buffer of pH 7.4. Dissolution profiles indicated that formulations F2 and F3 extended the drug release up to the desired time period of 12 h. DD Solver (an add-in software for MS Excel) was used to analyze the dissolution profile data for drug release kinetics such as first order, Zero-order, Higuchi and Korsmeyer–Peppas models. However, formulation (F3) containing HPMC – K4M as a matrix former showed concentration-independent drug release as highest linearity was observed when zero-order model was applied (R2 = 0.933). Release mechanism of formulations F3 was super case-II transport. Fourier transform infrared spectroscopy (FTIR) was used to assess the drug polymers compatibility and no drug– excipients interaction was found. The present study accomplished that ethylcellulose and HPMC can be used successfully to develop an extended release matrix tablet formulation.

Formulation and evaluation of matrix tablets of Eperisone hydrochloride

The aim of the present research is to develop and optimize Eperisone Hydrochloride extended release matrix tablets. Eperisone Hydrochloride is an antispasmodic drug mainly used to relieve pains it acts by relaxing the skeletal and smooth vascular muscles by blocking spinal reflexes drug which has oral bioavailability of 70% due to hepatic metabolism. Sustained release matrix tablets of Eperisone Hydrochloride were prepared through wet granulation technique by using HPMC K4M and EC as polymers, PVPK30 as binder, Magnesium stearate as lubricant and Talc as glidant. The granules of different formulations were determined for pre compression parameters. The prepared granules along with the excipients were then compressed. The formulated tablets were evaluated for physical characteristics viz. Hardness, Thickness, % Weight variation, Friability and the drug content. Furthermore the tablets evaluated for the in vitro release studies. Out of all the 8 formulations F7 showed desired characteristics in the physical parameters and in vitro drug release of 85.48% in 12hrs.The F7 dissolution data was best fitted to the Zero order model. The prepared Eperisone Hydrochloride matrix tablets found to be having a potential extended drug release.

Use of cellulose acetate butyrate as a carrier for preparation of alcohol-resistant matrix tablet

The objective of this study was to investigate cellulose acetate butyrate (CAB) as a carrier for extended-release alcohol-resistant matrix tablet. Powder blends were either directly compressed or granulated before compression. The drug release from CAB matrix tablet was robust to formulation/process parameters such as compression force (10−20 kN), granular size (0.15−1.40 mm), and drug content (50–70%). In addition, release medium variables such as ionic strength, pH, and agitation rate had no effect on the drug release. CAB matrix tablet was more robust than ethylcellulose matrix tablet; the release from CAB matrix tablet was not affected by ethanol content (up to 20% v/v) in the release medium irrespective of agitation. CAB is a promising polymer for formulating of alcohol-resistant extended-release matrix tablet.

Development and Optimization of Wax Matrix Tablets of Levetiracetam for Zero-order Controlled Release

The major objective of this work was to develop once-daily, extended-release tablets with zero-order drug release for levetiracetam using the wax matrix as the release retarding element. Extending drug release for highly water-soluble drugs is always a challenge. In this work, levetiracetam, a highly soluble drug, was chosen for which extended-release matrix tablets were developed using different waxes such as Compritol ATO 888, Imwitor 491, tristearin, and cetylpalmitateas rate controlling materials taken in different amounts. PEG 6000 was used to regulate water availability inside the wax matrix, and lactose was used as a pore-forming agent to aid the release of the drug from the wax matrix. Tablets were prepared by embedding the drug into the molten wax, followed by solidification, sieving, mixing with other excipients, and finally compression. The prepared tablets were tested for hardness, tensile strength, friability, drug content, and drug release studies. Type of wax, amount of wax, and PEG 6000 were optimized to achieve controlled drug release for about 24 hours. All the tablets showed good tensile strength in the range of 0.59–0.70 N/mm2, packing fraction in the range of 0.85–0.92, and friability in the range of 0.42–55%, indicating their solid physical integrity. The drug release studies indicated that the tablets prepared with tristearin showed better control among the waxes taken. The tablets containing 150mg of tristearin, 50mg of PEG 6000, and 50 mg of lactose showed controlled drug release for 24 hours with the zero-order release.

Formulation and Development of Extended Release Matrix Tablet of Carvedilol Phosphate

Carvedilol Phosphate, a non selective β-blocker drug under BCS class П and used in treatment of Hypertension. Solubility of the drug and its bioavailability is low. The purpose of the present study is to design extended release matrix tablet of Carvedilol Phosphate to improve gastric retention and reduce gastric emptying time. All blended formulations were evaluated for bulk density, tapped density, Carr’s index, angle of repose and the Hausner’s ratio. All these results indicated that, the powder blend showed good flow properties. All tablet formulations were evaluated for weight variation, hardness, Friability, Thickness, Content uniformity, In-vitro drug release. Regulated drug release in zero-order manner attained in the current study indicates that the optimized extended release tablet of Carvedilol Phosphate, prepared using Sodium carboxymethyl cellulose and HPMC K4M can successfully be employed in oral controlled release drug delivery system. Modified release ability of the formulation is likely to increase its GI residence time, and eventually, improve the extent of bioavailability.