Matrix Tablets Research Articles

Formulation and Evaluation of Bilayer Matrix Tablet of Vildagliptin and Acarbose

Formulation and Evaluation of Bilayer Matrix Tablet of Vildagliptin and Acarbose

Formulation and Evaluation of Extended Release Matrix Tablets of Lamotrigine

For extended release drug delivery systems, the oral route of drug administration has, by far received more attention as it is natural uncomplicated, convenient and safer route. Matrix tablets composed of drug and release retarding material (e.g. polymer) offer the simplest approach in designing the extended release system. Long-term adherence to anti-epilepsy drug (AED) regimens is frequently suboptimal. Poor adherence to therapy is associated with a number of negative consequences, including an increase in patient seizures and mortality. The present study was aimed to study the effect of Chitosan and Sodium Alginate on the release rate Lamotrigine for the preparation of extended release formulations. Matrix Tablets were prepared by wet granulation method and subjected for Physiochemical and in-vitro evaluation tests. The results were shown that the prepared were found to be within the pharmacopeial limit and with good release characteristics.

Functionality of wet-granulated disintegrant in comparison to directly incorporated disintegrant in a poorly water-soluble tablet matrix

Tablet disintegration is crucial for drug release and subsequent systemic absorption. Although factors affecting the disintegrant’s functionality have been extensively studied, the impact of wet granulation on the performance of disintegrants in a poorly water-soluble matrix has received much less attention. In this study, the disintegrants, crospovidone (XPVP), croscarmellose sodium (CCS) and sodium starch glycolate (SSG), were wet-granulated with dibasic calcium phosphate dihydrate as the poorly water-soluble matrix and polyvinylpyrrolidone as the binder. The effect of wet granulation was studied by evaluating tablet tensile strength and disintegratability. Comparison between tablets with granulated or ungranulated disintegrants as well those without disintegrants were also made. Different formulations showed different degrees of sensitivity to changes in tablet tensile strength and disintegratability post-wet granulation. Tablet tensile strength decreased for tablets with granulated disintegrant XPVP or CCS, but to a smaller extent for SSG. While tablets with granulated XPVP or CCS had increased disintegration time, the increment was lesser than for SSG, suggesting that wet granulation impacted a swelling disintegrant more. The findings showed that tablets with wet-granulated disintegrant had altered the disintegrant’s functionality. These findings could provide better insights into changes in the disintegrant’s functionality after wet granulation.

Film Coating of Phosphorylated Mandua Starch on Matrix Tablets for pH-Sensitive Release of Mesalamine.

Chemically modified mandua starch was successfully synthesized and applied to coat mesalamine-loaded matrix tablets. The coating material was an aqueous dispersion of mandua starch modified by sodium trimetaphosphate and sodium tripolyphosphate. To investigate the colon-targeting release competence, chemically modified mandua starch film-coated mesalamine tablets were produced using the wet granulation method followed by dip coating. The effect of the coating on the colon-targeted release of the resultant delivery system was inspected in healthy human volunteers and rabbits using roentgenography. The results show that drug release was controlled when the coating level was 10% w/w. The release percentage in the upper gastric phase (pH 1.2, simulated gastric fluid) was less than 6% and reached up to 59.51% w/w after 14 h in simulated colonic fluid. In addition to in vivo roentgenographic studies in healthy rabbits, human volunteer studies proved the colon targeting efficiency of the formulation. These results clearly demonstrated that chemically modified mandua starch has high effectiveness as a novel aqueous coating material for controlled release or colon targeting.

Methacrylic acid grafted inulin and carboxymethyl cellulose as additives in the development of pH sensitive hydrogel matrix for colon targeting

AbstractCompression‐coated matrix tablets were developed to target budesonide (BUD) in the colonic region using methacrylic acid (MAA) grafted inulin (INU) and carboxymethyl cellulose (CMC). INU was grafted with MAA to impart anionic characteristics to the gum, making it feasible to form a hydrogel by cross‐linking with calcium gluconate (CG). The core matrix made up of MAA‐g‐INU alone disintegrated within 30 min and the core matrix made up of CMC alone completely released BUD within 6 h. The combination of MAA‐g‐INU and CMC produced a rigid matrix, which was able to completely release BUD after 7 h. Compression coating of the core tablets with MAA‐g‐INU and CMC did not release BUD in the first 4 h, and complete BUD release took place in the next 4 h. Compression coating led to the formation of a rigid and viscous gel layer outside the core matrices, which hindered BUD release. We conclude that compression coating with CG cross‐linked CMC and MAA‐g‐INU could be used as a matrix for colonic delivery of drugs.Highlights Compression coated matrices were developed for colonic delivery of BUD. The matrix retained drug release up to 4 h in upper gastrointestinal tract (GIT). The matrix exhibited complete drug release in the next 4 h in the colon.

Formulation and Evaluation of Metformin Using Fenugreek Seed Mucilage Used as a Natural Polymer

The major goal of this study was to develop and test metformin sustained release tablets employing fenugreek seed mucilage (FSM) as a new binder, as opposed to standard polymers such as xanthan gum and HPMC. The study shows how FSM provides sustained medication release while keeping metformin physicochemical characteristics. The sustained-release matrix tablets were made on a laboratory scale utilizing the wet granulation process. 5 batches were created, each with varying quantities of fenugreek seed mucilage, xanthan gum, and HPMC. To examine the tablet's physical properties and consistency, different criteria such as thickness, hardness, weight variation, and content homogeneity were measured. FTIR tests were performed to determine the compatibility of metformin and the polymers employed. The results showed no incompatibility, indicating that the novel excipient, FSM was not affecting the drug's physicochemical qualities. The in-vitro drug dissolution investigation was conducted utilizing a USP type-II paddle apparatus to quantify the drug release rate from dosage forms and to assess thepolymers' efficacy in retarding drug release. The study discovered that raising the concentration ofthe matrix ingredient reduced the medication release rate. Among the formulations, the combination of FSM with HPMC (MS1) resulted in 95% drug release, FSM with xanthan gum achieved 96% drug release, and the MS4 formulation had the greatest drug release rate. Finally, the study showed that fenugreek seed mucilage and xanthan gum effectively develop metformin continuous-release matrix tablets. Lower concentrations of these polymers were more suited and effective, resulting in sustained drug release. This study demonstrates the potential of fenugreek seed mucilage as a novel and effective binder in sustained-release formulations.

Study on Natural Gums and Resins as Release Retarding Agents in Development of Sustained Release Matrix Tablets of Didanosine

Didanosine is an anti-retroviral drug which helpful in preventing human immunodeficiency virus (HIV) from multiplication in the body. This drug has a relatively short half-life and low absolute bioavailability and requires frequent dosing. So to avoid this frequent dosing and to improve the patient’s compliance, the development of sustained-release tablets is necessary. Natural gums and resins play an important role in retarding drug release. Didanosine extended-release matrix formulations developed with wet granulation using gum kondagogu, guar gum, gum olibanum, and olibanum resin, and evaluated for pre and post-compression parameters. The outcome of all evaluation tests is reached IP specifications. Formulations with kondagogu F1-F3 failed to extend the drug release. F4-F6 was formulated with gum kondagogu and guar gum, in which F4 prolonged the release up to 12 hours with 98.23%. The formulations F7 with olibanum resin release 96.13%, and F10 with gum olibanum releases 93.15% drug at the end of 12 hours. The conclusion from the study was that natural polymers could be used to enhance drug release for an extended period.

Formulation, design, and evaluation of valsartan sodium-sustained-release matrix tablets

The main aim of present work was to formulate and evaluate sustain release matrix tablets of Valsartan, an angiotensin II Receptor type 1 antagonist. Sustain release formulation are those which delivers the drug locally or systemically at a predetermined rate for a fixed period of time. The matrix tablet was prepared by direct compression method using by various concentration of chitosan and sodium alginate with combination of various release retardant polymer. The powder mixtures were subjected to various pre-compression parameters such as angle of repose, bulk density, tapped density and Carr’s index shows satisfactory result and the compressed tablets are evaluated for post-compression parameters such as weight variation, thickness, hardness, friability, drug content, in-vitro dissolution and stability studies. In-vitro dissolution studies were carried out for 24 hours using 0.1N HCl for first 2 hours and pH 6.8 phosphate buffers for 24 hours and the result showed that formulations F4 and F7 showed good dissolution profile to control the drug release respectively. Formulation containing higher concentration of chitosan and sodium alginate along with polymers sustainedthedrugreleasefor theperiodof24hours.The compatibilityof thedrug, polymers and other excipients were determined by FT-IR Spectroscopy. Results showed that the drug was compatible with polymers and other excipients. The release data was fitted to various mathematical models such as Zero-order, First-order, Higuchi equation and Korsmeyer- Peppas model to evaluate the kinetics and the drug release. The drug release followed first order and the mechanism was found to be non-Fickian. The stability studies were carried out for 3 months and result indicates that the selected formulations (F4and F7) were stable.

Formulation and Evaluation of Colon Targeted Matrix Tablet of Ornidazole

Formulation and Evaluation of Colon Targeted Matrix Tablet of Ornidazole

The influence of milling of ribbons on selected granule quality attributes and carvedilol release from roller-compacted hypromellose-based matrix tablets

Roller compaction is gaining importance in the pharmaceutical industry. This study evaluates the impact of ribbon milling conditions on properties of granules and compression mixtures and on drug release from hypromellose-based matrix tablets prepared with two different fillers. In the first part of the study, design of experiments (DoE) was utilized to investigate the effect of filler type (lactose and microcrystalline cellulose (MCC)), mill type (oscillating, conical and hammer mill), milling speed and the size of screen apertures on selected attributes (granule particle size distribution (PSD), porosity and shape), and on the compressibility and compactibility of compression mixtures. The effect of DoE factors and selected attributes on the release of carvedilol at different timepoints of the release profile (t = 1–7 h) was further assessed. The study showed that drug release was affected by filler type, mill type, and various attributes; however, their effect proved to be complex and strongly related to granule PSD. Therefore, this effect was minimized in the second part of the study, in which tablets containing the same amount of different particle size fractions of granules were prepared with different mills and fillers. The drug release profiles confirmed that drug release is mainly related to differences in filler type and granule PSD. However, they indicate that with lactose mill type also affected drug release, possibly due to differences identified in particle shape.

FORMULATION AND EVALUATION OF LOSARTAN POTASSIUM MATRIX TABLETS BY USING DIFFERENT POLYMERS

The study aims to create a sustained release matrix tablet for Losartan potassium, an angiotensin II receptor antagonist, to improve patient compliance and maintain therapeutic blood or tissue levels for extended periods. The research investigates the role of novel semi-synthetic polymers and natural polymers in comparison to well-known release retarding agents. Gastroretentive drug delivery systems (GRDDS) are unique technologies designed to improve drug bioavailability and absorption by avoiding the first-pass effect. Losartan potassium, an angiotensin II receptor antagonist, has a bioavailability of 32% and a low elimination half-life, making it suitable for oral controlled release. The study utilized natural and synthetic polymers in matrix tablet preparation, concentration, drug particles size, additives, and excipients to modify drug release. The powder mixtures were tested for pre-compression parameters and post-compression parameters, and in-vitro dissolution studies showed good dissolution profiles for drug release. Formulations with higher concentrations and polymers sustained drug release for 24 hours. FT-IR Spectroscopy confirmed drug compatibility with polymers and other excipients KEYWORDS: matrix tablets, Losartan Potassium, flow properties, pre compression parameters post compression parameters, In-vitro dissolution.

Diltiazem Hydrochloride Floating Matrix Tablet: Formulation and in vitro-in vivo Evaluation.

Diltiazem hydrochloride is a calcium channel-blocker with a plasma elimination half-life of 4.4 ± 1.3 h and has a narrow absorption window. So, this work aimed to prepare a gastro-retentive floating matrix tablet. The direct compression method was used to manufacture tablets. 32 factorial design was applied for optimization, taking Hydroxypropyl Methylcellulose K100M (HPMC K 100M) and the amount of sodium bicarbonate as independent factors and cumulative percentage release at 1 h, at 6 h, and at 12 h and floating lag time as dependent variables. The high amount of HPMC K100M and sodium bicarbonate shows good results. The optimized preparation was evaluated for differential scanning calorimetry, in-vivo gastric retention in male albino rabbits, kinetic modeling, and stability study. An in vivo study revealed gastric retention of tablets up to 6 h in healthy male Albino rabbits. The stability study indicated no significant change in the buoyancy and release profiles of the drug. From this study, it can be concluded that the gastro-retentive diltiazem hydrochloride floating matrix tablet was successfully prepared and retained inside the rabbit stomach for up to 6 h and was stable under accelerated stability study.

Review on Recent Advances of Sustained Release Matrix Tablet

A pharmaceutical dosage called a sustain-release matrix tablet is made to distribute drugs over a longer length of time. The design of these tablets ensures a steady and regulated release of active substances, decreasing side effects and lowering dosage frequency while maintaining therapeutic efficacy. The main features and disadvantages of sustain-release matrix tablets will be covered in detail in this review article. We have talked about a number of evaluations, including the in tablet dimensions, hardness, friability, homogeneous drug content, weight fluctuation, and swelling index. Sustained release matrix tablets are useful in a wide range of therapeutic contexts when a steady and extended release of the drug is necessary to preserve therapeutic efficacy, enhance patient compliance, and reduce adverse effects. The particular medication, the demands of the patient, and the intended therapeutic result all influence the decision to take such tablets.

Acute toxicity appraisal of Saussurea heteromalla extract and development of its chemotherapeutic herbal dosage form.

Ethnopharmacological relevance of Saussurea species for anti-cancer compounds instigated us to develop chemotherapeutic herbal tablets. This study was an ongoing part of our previous research based on the scientific evaluation of Saussurea heteromalla (S. heteromalla) for anti-cancer lead compounds. In the current study, S. heteromalla herbal tablets (500 /800 mg) were designed and evaluated for anti-cancer activity. Arctigenin was found as a bioactive lead molecule with anti-cancer potential for cervical cancer. The in vitro results on the HeLa cell line supported the ethnopharmacological relevance and traditional utilization of S. heteromalla and provided the scientific basis for the management of cervical cancer as proclaimed by traditional practitioners in China. LD50 of the crude extract was established trough oral acute toxicity profiling in mice, wherein the minimum lethal dose was noticed as higher than 1000 mg/kg body weight orally. Chromatographic fingerprint analysis ensured the identity and consistency of S. heteromalla in herbal tablets in terms of standardization of the herbal drug. About 99.15% of the drug (S. heteromalla crude extract) was recovered in herbal tablets (RSD: 0.45%). In vitro drug release profile was found to be more than 87% within 1 h, which was also correlated with different mathematical kinetic models of drug release (r2 = 0.992), indicating that drug release from matrix tablets into the blood is constant throughout the delivery. The dosage form was found stable after an accelerated stability parameters study which may be used for anti-cervical cancer therapy in the future, if it qualifies successful preclinical investigation parameters.

Mechanistic Investigation of Enzyme Triggered Release from a Xyloglucan Matrix Tablet for Controlled Colonic Drug Delivery

The objective of this study was to investigate the mechanisms underlying drug release from a controlled colonic release (CCR) tablet formulation based on a xyloglucan polysaccharide matrix and identify the factors that control the rate of release for the purpose of fundamentally substantiating the concept and demonstrating its robustness for colonic drug delivery. Previous work demonstrated in vitro limited release of 5-aminosalicylic acid (5-ASA) and caffeine from these tablets in small intestinal environment and significant acceleration of release by xyloglucanase, an enzyme of the colonic microbiome. Targeted colonic drug delivery was verified in an animal study in vivo. In the present work, interaction of the xyloglucan matrix tablets with aqueous dissolution media containing xyloglucanase was found to lead to the spontaneous formation of a hydrated highly viscous gummy layer at the surface of the matrix which had a reduced drug content compared to the underlying regions and persisted with a nearly constant thickness that was inversely correlated to the enzyme concentration throughout the duration of the release process. Enzymatic hydrolysis of xyloglucan was determined to take place at the surface of the matrix leading to matrix erosion and a relation for the rate of enzymatic reaction as a function of bulk enzyme concentration and the concentration of dissolved xyloglucan in the gummy layer was derived. A mathematical model was developed encompassing aqueous medium ingress, matrix metamorphosis due to xyloglucan dissolution and matrix swelling, enzymatic hydrolysis of the polysaccharide and concomitant drug release due to matrix erosion and simultaneous drug diffusion. The model was fitted to data of reducing sugar equivalents in the medium reflecting matrix erosion and released drug amount. Enzymatic reaction parameters and reasonable values of medium ingress velocity, xyloglucan dissolution rate constant and drug diffusion coefficient were deduced that provided an adequate approximation of the data. Erosion was shown to be the overwhelmingly dominant drug release mechanism while the role of diffusion marginally increased at low enzyme concentration and high drug solubility. Changing enzyme concentration had a rather weak effect on matrix erosion and drug release rate as demonstrated by model simulations supported by experimental data, while xyloglucan dissolution was slow and had a stronger effect on the rate of the process. Therefore, reproducible colonic drug delivery not critically influenced by inter- and intra-individual variation of microbial enzyme activity may be projected.

New Hydrophilic Matrix Tablets for the Controlled Released of Chlorzoxazone.

The modified release of active substances such as chlorzoxazone from matrix tablets, based on Kollidon®SR and chitosan, depends both on the drug solubility in the dissolution medium and on the matrix composition. The aim of this study is to obtain some new oral matrix tablet formulations, based on Kollidon®SR and chitosan, in order to optimize the low-dose oral bioavailability of chlorzoxazone, a non-steroidal anti-inflammatory drug of class II Biopharmaceutical Classification System. Nine types of chlorzoxazone matrix tablets were obtained using the direct compression method by varying the components ratio as 1:1, 1:2, and 1:3 chlorzoxazone/excipients, 20-40 w/w % Kollidon®SR, 3-7 w/w % chitosan while the auxiliary substances: Aerosil® 1 w/w %, magnesium stearate 0.5 w/w % and Avicel® up to 100 w/w % were kept in constant concentrations. Pharmaco-technical characterization of the tablets included the analysis of flowability and compressibility properties (flow time, friction coefficient, angle of repose, Hausner ratio, and Carr index), and pharmaco-chemical characteristics (such as mass and dose uniformity, thickness, diameter, mechanical strength, friability, softening degree, and in vitro release profiles). Based on the obtained results, only three matrix tablet formulations (F1b, F2b, and F3b, containing 30 w/w % KOL and 5 w/w % CHT, were selected and further tested. These formulations were studied in detail by Fourier-transform infrared spectrometry, X-ray diffraction, thermogravimetry, and differential scanning calorimetry. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The results were analyzed by fitting into four representative mathematical models for the modified-release oral formulations. In vitro kinetic study revealed a complex mechanism of release occurring in two steps of drug release, the first step (0-2 h) and the second (2-36 h). Two factors were calculated to assess the release profile of chlorzoxazone: f1-the similarity factor, and f2-the factor difference. The results have shown that both Kollidon®SR and chitosan may be used as matrix-forming agents when combined with chlorzoxazone. The three formulations showed optima pharmaco-technical properties and in vitro kinetic behavior; therefore, they have tremendous potential to be used in oral pharmaceutical products for the controlled delivery of chlorzoxazone. In vitro dissolution tests revealed a faster drug release for the F2b sample.

Exploring the Effectiveness of Carboxymethylated and Crosslinked Albizia procera Gum in Diltiazem Hydrochloride Matrix Tablets: A Comparative Analysis.

This study investigates the efficacy of modified Albizia procera gum as a release-retardant polymer in Diltiazem hydrochloride (DIL) matrix tablets. Carboxymethylated Albizia procera gum (CAP) and ionically crosslinked carboxymethylated Albizia procera gum (Ca-CAP) were utilized, with Ca-CAP synthesized via crosslinking CAP with calcium ions (Ca2+) using calcium chloride (CaCl2). Fourier Transform (FT) IR analysis affirmed polymer compatibility, while differential scanning calorimetry (DSC) and X-ray diffraction (XRD) assessed thermal behavior and crystallinity, respectively. Zeta potential analysis explored surface charge and electrostatic interactions, while rheology examined flow and viscoelastic properties. Swelling and erosion kinetics provided insights into water penetration and stability. CAP's carboxymethyl groups (-CH2-COO-) heightened divalent cation reactivity, and crosslinking with CaCl2 produced Ca-CAP through -CH2-COO- and Ca2+ interactions. Structural similarities between the polymers were revealed by FTIR, with slight differences. DSC indicated modified thermal behavior in Ca-CAP, while Zeta potential analysis showcased negative charges, with Ca-CAP exhibiting lower negativity. XRD highlighted increased crystallinity in Ca-CAP due to calcium crosslinking. Minimal impact on RBC properties was observed with both polymers compared to the positive control as water for injection (WFI). Ca-CAP exhibited improved viscosity, strength, controlled swelling, and erosion, allowing prolonged drug release compared to CAP. Stability studies confirmed consistent six-month drug release, emphasizing Ca-CAP's potential as a stable, sustained drug delivery system over CAP. Robustness and accelerated stability tests supported these findings, underscoring the promise of Ca-CAP in controlled drug release applications.

In vitro Modified Release Studies on Melatoninergic Fluorinated Phenylalkylamides: Circumventing their Lipophilicity for Oral Administration.

In an attempt to circumvent the lipophilicity burden for the oral administration of new potent synthetic melatoninergic fluorine-substituted methoxyphenylalkyl amides, we conducted in vitro modified release studies using carefully selected matrix tablets' biopolymeric materials in different ratios. In particular, we sought to attain release profiles of these analogues similar to that of the parent compound, the chronobiotic hormone Melatonin (MLT), and also of the commercially available drug, Circadin®. It was found that some of these systems, albeit being more lipophilic than MLT, mimic the in vitro release patterns of melatonin and Circadin®. Moreover, a number of these derivatives were proven suitable for dealing with sleep onset problems, whilst others for dealing with combined sleep onset/sleep maintenance dysfunctions.

Modulation of mesalamine release from enteric-coated matrix tablets using natural polysaccharides for localized colonic delivery

Background: Inflammatory bowel diseases (IBD) require effective colon-targeted drug delivery for improved therapeutic efficacy and minimized systemic side effects. Objectives: The objective of this research was to develop and evaluate novel colon-targeted matrix tablet formulations of mesalamine (5-aminosalicylic acid) for the treatment of IBD. Materials and Methods: Mesalamine matrix tablets were prepared by wet granulation technique using pH-sensitive polymers (HPMC K4M) and biodegradable natural polysaccharides (pectin, chitosan, and guar gum). Tablets were characterized for physicochemical properties, drug content, and in vitro drug release. Compatibility studies using FTIR and DSC confirmed no interaction between mesalamine and polymers. The optimized formulations were enteric-coated with Eudragit S100 and ethyl cellulose. Drug release kinetics and stability studies were conducted. Results and Discussion: The uncoated formulations (M3, M6, M7) showed adequate protection against drug release in simulated gastric (0-2 h) and intestinal (2-5 h) fluids. The enteric-coated formulations (ME3, ME6, ME7) exhibited a lag time of around 2 hours and restricted drug release (<5%) in simulated gastric and intestinal fluids up to 5 hours. However, in simulated colonic fluid (pH 6.8) containing 4% rat cecal contents, these formulations showed enhanced drug release (71-83% in 12 h) due to biodegradation of polymeric matrices by colonic enzymes. Drug release kinetics indicated anomalous transport or super case-II transport mechanisms. Stability studies at 40°C/75% RH for 3 months revealed no significant changes. Conclusion: The developed colon-targeted mesalamine matrix tablets demonstrated the potential to protect the drug from release in the upper GIT while facilitating targeted drug delivery to the colon, which could improve therapeutic efficacy and minimize systemic side effects in the treatment of IBD.

Formulation Strategies for Sustained-Release Tablet Dosage Forms

Sustained-release or extended-release tablet formulations are designed to release the active pharmaceutical ingredient at a slower rate and over an extended period compared to conventional immediate-release dosage forms. This controlled drug delivery approach offers several advantages including improved patient compliance, maintenance of therapeutic drug levels, reduced side effects, and protection of drug molecules from degradation. [1,2] Various formulation approaches have been explored for achieving sustained drug release from tablet matrices. This review discusses key formulation aspects like rate-controlling polymers, factors influencing drug release, manufacturing techniques, and recent advances aided by quality-by-design principles and mathematical modeling for optimizing sustained-release profiles. Regulatory considerations for evaluation and approval are also highlighted