Matrix Tablets Research Articles

Drug Extended-Release System Utilizing Micelle Formation of Highly Water-Soluble Drugs and a Counter Polymer.

The objective of this study is to clarify the mechanism of extending release of highly water-soluble drugs via counter polymer (CP) utilization in poly(ethylene oxide) (PEO)/polyethylene glycol (PEG) matrix tablets. Carbomer, poly(acrylic acid), was used as a CP, which has the opposite charges to the drugs. The in vitro release of several highly water-soluble drugs from PEO/PEG tablet with or without CP were tested, the relationship between the sustained release effect by a CP (SRE) and the physicochemical properties of the drugs was investigated. The results demonstrated that the utilization of CP can extend the release of some highly water-soluble drugs by effectively controlling the drug diffusion through matrices. On the other hand, the effectiveness of CP was different depending on the drugs applied. There were not statistical correlations between SRE and physicochemical properties such as solubility, molecular weight, and charge intensity of the drugs, while a micelle forming property of the drugs played an important role in SRE by CP. It was concluded that CP, Carbomer, having negative charges could effectively interact with opposite charges on the surface of stable drug micelles, which could result in a significant decrease in drug diffusion leading to extended drug release. It is considered that the system utilizing CP is a promising approach to achieve extended release of highly water-soluble drugs with a reasonable tablet size, especially in the case of large drug loading.

IVIVC assessment, pharmacokinetic evaluation, and X-ray radiography mapping of Novel Parteck® SRP 80 and hypromellose-loaded LTD4 receptor antagonist chronosystem

BackgroundThe current research aims to determine the pharmacokinetic parameters, mucoadhesive strength, and IVIVC correlation of the novel chronotherapeutic drug delivery system of montelukast sodium (MTS) loaded Parteck® SRP80 and hypromellose system. To accomplish this, an HPLC method was developed which is highly sensitive, precise, and rapid for quantifying pure MTS in rabbit plasma. Mucoadhesive strength and time-dependent mobility of developed formulation were established by ex-vivo study and X-ray radiography, respectively. Using a fraction of drug absorbed (FDA) and a fraction of drug released (FDR), Level-A in-vitro in-vivo correlation (IVIVC) was developed. According to ICH Q1A (R2) standards, stability experiments were conducted for 180 days.ResultMTS retention time came as 3.971 min with a mobile phase of methanol: acetonitrile: 0.2 mM sodium acetate buffer (5:90:5). In-vitro dissolution showed pulsatile release of the drug up to 24 h with two lag phases. The in-vivo study showed a Cmax of 490.16 ± 33.95 ng/ml, Tmax of 9 h, and MRT of 14.08 ± 1.21 h. The correlation coefficient of 0.9899 confirmed the level-A IVIVC. Uncoated matrix tablet of Parteck® SRP 80 displayed mucoadhesive strength 1.25-fold higher than hypromellose. Stability experiments found no significant changes in drug content, physical appearance, and cumulative percentage release with a similarity factor of 87–90.ConclusionA single oral dose in-vivo study proved the sustained release of the drug for 24 h with satisfactory mucoadhesive strength. Moreover, X-ray radiography has confirmed the time-dependent presence of formulation at the needed spot. This study fulfilled all the requirements for chronotherapy of asthma and can be scaled up in the future.Graphical abstract

Formulation and Evaluation of Sustained Release Matrix Tablet of Valsartan

The aim of this study was to develop antihypertensive matrix tablets with sustained release of valsartan, an angiotensin type II receptor antagonist, using hydroxypropyl methylcellulose and combination of ethyl cellulose material as matrix in different proportions by wet granulation. The granules are evaluated by tapped density, bulk density, angle of repose and compressibility index. The tablets are tested for friability, hardness, weight variation and in vitro release. The granules showed good flow properties and compressibility properties and all tablet formulations showed pharmaceutical properties. The result of dissolution study indicate that the formulation prepared by combination of high grade HPMC K100M and ethyl cellulose showed maximum drug release for 12hrs and high drug release around 98.56% i.e., Formulation F8 is the best formulation.

Developmental strategy for swellable/erodible matrix tablet of mirabegron: quality by design approach with various geometric properties and pharmacokinetic evaluation

Developmental strategy for swellable/erodible matrix tablet of mirabegron: quality by design approach with various geometric properties and pharmacokinetic evaluation

In-vitro evaluation of co-excipients for release of donepezil hydrochloride from Carbopol 974P based tablets

The prime aims of the present work at formulating and preparing matrix tablets using Carbopol 974P to sustain the release of donepezil HCl. Tablets were prepared by direct compression method and evaluated for the effects of ingredients on the in-vitro release behavior. Gelatin, α-cellulose, sodium alginate, hydroxyapatite, and natural zeolite (clinoptilolite) were used as co-excipients to modulate the formulations. The prepared tablets of the 10 formulations were characterized by using Fourier transform infrared spectroscopy (FT-IR), digital microscope and scanning electron microscopy (SEM) techniques. The drug release kinetics was analyzed using Zero-order, First-order, Hixson-Crowell and Peppas models. The result indicated that the drug release rates highly depended on the polymers and pH medium. In addition, it was obtained that the combination of Carbopol 974P and gelatin retarded the drug release. So, these matrix tablets can reduce the dose intake. Thus, these matrix tablets are a promising release of donepezil HCl.

Grafted tamarind kernel polysaccharide based Al3+ cross-linked hydrogel matrices for sustained release of drug in the gastrointestinal milieu

Ionically cross-linked hydrogel serves as an excellent matrix material for the sustained delivery of drugs. Tablets prepared with tamarind kernel polysaccharide (TKP) as the sole matrix material could not provide sustained release of the incorporated drugs. The purpose of the work was to modify TKP and development of ionically cross-linked hydrogel matrix tablets for sustained drug delivery. Grafting of TKP was performed with methacrylic acid (MAA) following the free radical polymerization technique. Hydrogel matrix tablets using Al3+ ion cross-linked grafted TKP were prepared by direct compression method. Al3+ ions were found to considerably influence the erosion, swelling, and paracetamol release from the matrix tablet. Retardation of the erosion, swelling, and paracetamol release was observed with increasing the concentration of Al3+ ions. The hydrogel matrix tablets showed a slow release of drugs in an acidic medium and a relatively faster drug release in an alkaline medium. The optimized formulation having a co-polymer/aluminium hydroxide (Al(OH)3) ratio of 1:1, exhibited sustained drug release action for more than 10 h with lower swelling and erosion of the gel matrix. We conclude that Al3+ ion cross-linked grafted TKP is an excellent matrix material for sustained delivery of drugs in the gastrointestinal milieu.

Formulation and Evaluation of Miglitol Sustained Release Matrix Tablets Using Moringa Oleifera Gum

Formulation and Evaluation of Miglitol Sustained Release Matrix Tablets Using Moringa Oleifera Gum

Effect of intragranular/extragranular tara gum on sustained gastrointestinal drug delivery from semi-IPN hydrogel matrices

The present research was undertaken to develop semi-IPN hydrogel matrix tablets of tara gum (TG) and carboxymethyl TG (CMTG) for sustained gastrointestinal delivery of highly water soluble tramadol hydrochloride (TH). The matrix tablets were developed by a hybrid process of wet granulation and direct compression technique. Carboxymethyl TG was crosslinked with dual cross-linking ions (Al3+/Ca2+). The uncross-linked component of the semi-IPN matrix was either incorporated within the granules (intragranular TG) or incorporated outside the granules (extragranular TG), prior to compression. The effect of intragranular/extragranular TG on the swelling, erosion and TH release characteristics from the semi-IPN hydrogel matrix tablets was investigated. The key finding of the investigation indicated that intragranular TG expedited TH release, while extragranular TG sustained TH release. Moreover, the effect of cross-linking ions on viscosity, rigidity, cross-link density and TH release behavior from hydrogel matrices was investigated. In-vivo pharmacokinetic performance of the optimized extragranular TG semi-IPN hydrogel matrix (F15) indicated sustained TH release in gastrointestinal milieu.

Preparation and in-vitro evaluation of dyphylline controlled release matrix tablets

Preparation and in-vitro evaluation of dyphylline controlled release matrix tablets

Evaluation of Cassia fistula seed galactomannan as tablet-binder in formulation of diclofenac sodium-loaded monolithic matrix tablet

The present study aimed to evaluate Cassia fistula seed galactomannan (CFSG) as a tablet-binder in the formulation of a monolithic matrix tablet using diclofenac sodium as a model drug. Initially, CFSG was extracted and purified from the seeds of the Cassia fistula tree and then screened for phytochemicals. Native CFSG was characterized with polysaccharide content determination, monosaccharide composition analysis, elemental analysis, FTIR, solid-state 13C NMR, molecular weight, zeta potential, DSC, TGA-DTA, XRD, viscosity, pH and surface tension, rheology, SEM and acute oral toxicity study. Prior to formulation, the drug-CFSG compatibility was checked by FTIR, DSC, and XRD. Diclofenac sodium-loaded granules were prepared by the wet granulation method and evaluated for various granule properties. Finally, granules were compressed into tablets and evaluated for binding and other tablet properties. The granules showed to have optimum micromeritic properties. Tablet hardness and friability were found to be approximately 7 kg/m2 and 0.3 %, respectively, which substantiate the excellent binding capacity of CFSG. Other tablet properties were also found to be within the Pharmacopoeial compliance limit. The tablets with a minimum concentration of CFSG (2.5%w/w) as binder showed appreciable mechanical strength and faster drug release, which ratifies CFSG as an alternative tablet binder.

Formulation and Evaluation of Propranolol Hydrochloride Sustained Release Matrix Tablets Using Different Grades of HPMC and MCC

Formulation and Evaluation of Propranolol Hydrochloride Sustained Release Matrix Tablets Using Different Grades of HPMC and MCC

Formulation and Development of Flurbiprofen Colon-Specific Eudragit Coated Matrix Tablets: Use of a Novel Crude Banana Peel Powder as a Time-Dependent Polymer.

The rationale for the current investigation is to study the crude banana peel (CBP) powder efficiency as a novel natural time-dependent polymer along with a pH-sensitive polymer to develop flurbiprofen colon-specific tablets. The direct compression method is utilized to prepare the flurbiprofen-CBP matrix tablets using 9mm punches on the rotary tableting machine and subsequently coated with Eudragit® S 100 by a dip coating method. The tablets were evaluated for various tableting properties and in vitro drug release studies. From the results of dissolution studies, the F6 formulation showed negligible drug release (5.76% in 5h) in the upper gastrointestinal tract and progressive release in the colon (99.08% in 24h). Mean dissolution time, T10%, and T80% were found to be 13.33h, 5.8h, and 20.7h, respectively, which explains the efficiency of the present combination of polymers for colon-specific drug release. From the dissolution studies results of stability studies, the similarity index was calculated and found to be 74.75. In conclusion, utilizing CBP as a natural, time-dependent polymer in conjunction with Eudragit® S 100 to develop the flurbiprofen tablets seems like a promising approach for delivering drugs specifically to the colon.

Formulation and Optimization of Matrix Tablets Based on Spirulina and Vitamin C

Spirulina is a type of algae widely consumed around the world as a dietary supplement due to its great nutritional potential. However, it does not contain vitamin C, a vital vitamin for the proper functioning of the human body, particularly given its immunostimulant potential. The objective of this work was to formulate sustained release spirulina–vitamin C matrix tablets that would enhance particularly a prolonged release and better absorption of vitamin C. A galenic formula based only on vitamin C was made, and then the proportion of vitamin C was reduced in favor of spirulina powder. The manufactured tablets were then subjected to various pharmacopeial quality control tests. The results of these tests showed a good distribution of the powder mixtures in the formulated tablets (i.e., mass uniformity test) and satisfactory outcomes were found for the content uniformity, disintegration and dissolution tests (with 45 % of vitamin C dissolved after 4 hours). Only the results for the friability test were unsatisfactory, indicating the need to improve the physical properties of the powders before compression. These findings open a new area for developing supplementary dietary. 
 Keywords: Spirulina, Vitamin C, Matrix tablet, Quality control.

Facile fabrication of an extended-release tablet of Ticagrelor using three dimensional printing technology.

The objective of the study was to fabricate tailored extended-release tablets of blood thinner Ticagrelor as once-daily dosing using additive manufacturing for better compliance in heart failure therapy. The solid work design of the tablet was printed using hot melt extrusion (HME) based 3D printing by optimized mixture of Eudragit RS-100, plasticizer and drug for producing extrudable and printable filaments. FTIR and TGA results showed no covalent interaction among ingredients and no decomposition during HME process, respectively. Friability, weight variation, assay and content uniformity tests met USP requirements, while the mean hardness of the tablets was calculated in a value between 40 and 50 kg. According to DSC and XRD results, the crystallinity state of the Ticagrelor was converted to an amorphous one in the tablet matrix. Smooth surfaces with multiple deposited layers were observed using SEM. In comparison, the maximum Ticagrelor release of 100% after 120 min from Brilinta® tablets was decreased to 97% in 400 min from the 3D tablet at infill of 90%. Korsmeyer-Peppas kinetic model showed the drug release mechanism is affected by diffusion and swelling. In general, fabrication of the extended-release 3D printed tablet of Ticagrelor using HME-based-additive manufacturing has the potential to provide specific doses with tailored kinetic release for personalized medicine, improving adherence at point-of-care.

Green method for evaluation of marbofloxacin tablets by HPLC and evaluation of interchangeability with UV and turbidimetric methods.

Marbofloxacin (MAR) is a veterinary antimicrobial, marketed in injectable solution, oral suspension and tablets. MAR has no monograph for tablets evaluation in official compendiums. HPLC methods present in the literature for evaluating MAR in tablets do not follow the principles of green and sustainable analytical chemistry. A green, clean and sustainable method by HPLC was developed and validated to evaluate the content and stability of MAR in tablets, in addition to comparing it with other methods available in the literature. A C8, 5 µm, 4.6 x 150 mm (ACE®) colunn, purified water with 0.2% formic acid: ethanol (70:30, v/v) as mobile phase, flow rate of 0.7 mL/min at 296 nm were used. The method was linear over a concentration range of 1-10 μg/mL, selective for tablet matrix and forced degradation, precise with relative standard deviations less than 5%, accurate with recovery of 99.99% and robust to changes in the mobile phase, flow rate, wavelength, equipment and column brand. The retention time for MAR was approximately 3.1 minutes. The method can be used in routine analysis of MAR in tablets in chemical-pharmaceutical laboratories. Furthermore, it can be used to verify the stability of MAR-based products and proved to be interchangeable with spectrophotometric method in the UV region and turbidimetric microbiological method. Additionally, it is a clean method, which contemplates green analytical chemistry.

High-speed optical observations of asymmetric pulsations of microbubbles released from tablet matrix

Abstract Microbubbles with a negligible shell are of utmost importance in the study of harmonic ultrasound contrast agents. The purpose of this study was to collect and quantify experimental pulsation footage of gas microbubbles released from tablet matrix under sonication. Radii were measured as a function of time of 50 microbubbles that had been released from tablet matrix and were subjected to 3-cycle pulses of 1-MHz ultrasound with a 0.3-MPa peak-negative pressure. The size distribution was measured, as well as pre- and postsonication radii. The experimental footage showed proof of asymmetric buckling, but also of excursion-only behaviour. The former phenomenon has been attributed to a surplus of material accumulated on the microbubble-liquid interfaces, whilst the latter phenomenon has been associated with the presence of incompressible material inside the microbubbles. The postsonication resting radii of 41 microbubbles had become less compared to the corresponding pre-sonication radii. The opposite effect was observed with eight microbubbles in the same size range. This feasibility study confirmed that the gas microbubbles released from tablet matrix may pulsate asymmetrically. Thus, they might be suitable tracers for harmonic imaging.

Formulation and Evaluation of Cola acuminata Gum-based Mucoadhesive Sustained-release Matrix Tablets of Diclofenac Sodium.

This study aimed to evaluate Cola acuminata gum (CAG) for the formulation of mucoadhesive sustained-release matrix tablets of diclofenac sodium. Different batches of granules containing CAG and 100 mg of DS in ratios 0.5:1, 1:1, 2:1, and 3:1 were prepared, compressed into tablets, and evaluated for mucoadhesive strength, swelling index, and drug release in SGF (pH 1.2) and SIF (pH 7.4). Swelling indices and mucoadhesive strengths of the tablets were pH-dependent. Swelling indices of 56 ± 2.03 to 121 ± 2.19% and mucoadhesive strengths of 7.25 ± 1.45 to 15.43 ± 2.71 g/cm2 obtained at pH 7.4 were significantly higher (p<0.05) than swelling indices of 25 ± 2.43 to 47 ± 3.15% and mucoadhesive strengths of 5.52 ± 0.76 to 9.22 ± 1.95 g/cm2 obtained at pH 1.2. The percentage release of DS from the matrix tablets at pH 1.2 after 2 h (T2h) was insignificant. However, the percentage of drug release at pH 7.4 was significant for all the batches and dependent on the CAG concentration. The drug release was in the order of batches containing 3 g (80.44 ± 7.75) < 2 g (86.35 ± 5.65) < 1 g (90.08 ± 6.14) < 0.5 g (99.70 ± 3.90). The time for maximum drug release was 7 h (T7h) for CAG containing 0.5 g and 10 h (T10h) for other batches. This study showed that CAG could be useful for mucoadhesive sustained drug delivery.

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.

Polymer Tablet Matrix Systems for the Controlled Release of Dry Betula pendula Leaf Extract.

The aim of the study was to develop polymer matrix tablets with modified release of dry Betula pendula leaf extract and to investigate basic parameters influencing the drug release pattern. To fully assess the statistical significance of the influence of the individual factors in the tablet formulation development as well as the combination of them, Tukey's tests and a complete 33 factor analysis of variance (ANOVA) were applied. The following three factors were studied at three levels (low, medium and high): influence of the hydrophobic/hydrophilic polymer ratio Ethylcellulose (EC)/Hydroxypropyl methylcellulose (HPMC) (40/60, 25/75 and 10/90), influence of HPMC molecular weight (500 kDa, 750 kDa and 1150 kDa), and influence of the compression force applied (1 t, 1.5 t and 2 t). The effect of these varied parameters on the drug release parameter t80 was evaluated statistically. Twenty-seven tablet models were formulated, including all possible combinations of the variables. The obtained drug release profiles demonstrated that a 25/75 (EC/HPMC) ratio was the most suitable for prolonging the release process. Increasing the molecular weight of HMPC from 500 kDa to 750-1150 kDa and applying higher compression force significantly influenced the studied t80 values and caused sustained drug release (t80 up to 7.97 h). The combination of the hydrophilic HPMC polymer with the hydrophobic EC can result in the formation of a promising drug-carrying matrix, offering effective control of the drug release process.

Controlled Release Matrix Formulation of Paliperidone in Concurrence with Regulatory Requirements

Paliperidone is the 9-hydroxy metabolite (9-hydroxy) of risperidone and is a psychotropic drug of the atypical antipsychotic family. Paliperidone has the racemates (+)- and (-)-paliperidone. It is a dopamine D2 antagonist with serotonergic 5-HT2A antagonistic action that acts centrally. ALZA OROS® osmotic medication release technology is used to create Invega ER tablets. It is a tri-layer longitudinally compressed tablet based on a sophisticated osmotic delivery method that is meant to administer the paliperidone in a defined way over 24 hours. This research aims to create a generic controlled-release single-layer matrix tablet of paliperidone. Different combinations of Polyox and hypromellose in the core were used, followed by coating, to assist/build a stable and strong formulation. All strengths have similar in-vitro dissolution profiles. Freeze formulation was assessed for nitrosamine risk assessment as well as challenge for alcohol dose dumping study. Paliperidone is a basic compound with a pKa1 of 8.2 (piperidine moiety) and a pKa2 of 2.6 (pyrimidine moiety). As a result, a substantial portion of the molecule is ionized at physiological pH. It is relatively insoluble in water (0.003 g/100 mL water at pH 7.4). The solubility decreases at higher pH (0.001 g/100 mL at pH 12.9) and significantly increases at lower pH (3 g/100 mL at pH 5.3). The partition coefficient octanol/water (log P) is 2.39. Hence, discriminating media was identified as pH 2.75 buffer. The Higuchi model was used for expressing the in-vitro release profile through matrix composition. Formulation withstands 0–40% alcoholic conditions under in-vitro release tests. It is easy to formulate, stable and cost-effective. The manufacturing process involves dry blending followed by compression and coating so there will be the least chemical interaction of an active substance with other excipients. Hence, there is a negligible possibility to generate nitrosamine impurity in the formulation. The formulation is classified as rugged against dose dumping.