Bilayer Tablets Research Articles

Formulation and Evaluation of Extended-Release Bilayer Tablets Containing Empagliflozin and Metformin Hydrochloride for Diabetes Mellitus Management

Formulation and Evaluation of Extended-Release Bilayer Tablets Containing Empagliflozin and Metformin Hydrochloride for Diabetes Mellitus Management

Formulation and Evaluation of Gastroretentive Bilayer Tablets

Gastroretentive bilayer tablets were designed to prolong the gastric residence time after oral administration and to achieve immediate release of lansoprazole and controlled release floating layer of clarithromycin to treat gastric ulcers. Instant release layer has a combination of super disintegrating agents. A combination of effervescent mechanism is used. HPMC K5 was used as swelling polymer and citric acid, sodium bicarbonate as gas generating agent to reduce the floating lag time. Bilayer floating tablets were prepared with varying proportions of instant layer and sustained release floating approaches. The prepared formulations were evaluated for various tablet and floating parameters. Tablet properties were found to be within the limits according to procedures prescribed in USP. They had a floating lag time around 3-7 seconds and floating time more than 24 hours. The cumulative % drug release in simulated gastric fluids after 10 hours was 70% - 95%. The mechanism of drug release was analyzed by fitting the release data into various kinetic models. It was found that all the formulations best fit the Higuchi’s model. Keywords: Gastroretentive drug delivery system; Bilayer tables, Instant release layer, Floating layer, Lansoprazole, Clarithromycin.

Understanding Excipient-Induced Crystallization of Spray-Dried Amorphous Solid Dispersion

This study investigates the compatibility of excipients with the model system SDI-X and their role in the induced crystallization of the amorphous compound-X in tablet formulations. We aimed to establish a straightforward and practical screening approach for evaluating excipient-induced crystallization of SDI in tablet matrices. Three methodologies—binary powder mixture, binary compact, and bilayer tablets—were employed to qualitatively and quantitatively evaluate the recrystallization of SDI-X with various excipients under accelerated storage conditions. The results demonstrated that binary compacts, providing direct physical contact between SDI-X and excipients, are superior in reflecting realistic drug-excipient contact within pharmaceutical tablets, enabling a more accurate assessment of excipient-induced crystallization for SDI-X. In contrast, the broadly used conventional binary blends can significantly underestimate this risk due to insufficient proximity. In addition, the bilayer tablets further confirmed that crystallization initiates at the contact surface between SDI-X and the excipients. The study highlighted that not only hygroscopicity but also the type of excipient and its physical contact with SDI-X significantly influence the recrystallization extent and rate of SDI-X. Interestingly, less hygroscopic diluents such as mannitol and lactose induced much higher levels of crystallization of SDIs, contrary to expectations based on moisture content alone. This suggests that the excipient type and contact surface are more critical in inducing recrystallization than just the level of moisture. The findings emphasize the need for careful excipient selection, study design, and sample preparation to enable appropriate assessments of SDI-excipient compatibility.

Formulation and development of bilayer tablet containing irbesartan and metformin hydrochloride for diabetic hypertensive patients

Background: Hypertension is a common complication of type II diabetes. The present research work aimed to develop bilayer tablets that would manage type II diabetes patients with hypertension. The prepared bilayer tablet has an immediate-release layer of anti-hypertensive irbesartan and a sustained-release (SR) layer of anti-diabetic metformin hydrochloride. The purpose of these bilayer tablets was to increase patient compliance by converting two separate monotherapy to single combination therapy. Methodology: Several ratios of polymers, including HPMC K100M, EC, Eudragit, and Guar gum, were employed to prolong the drug release for twelve hours. An immediate-release layer of irbesartan was prepared by spherical agglomeration. The physical properties, drug content, solubility profiles, release kinetics, and stability of prepared bilayer tablets were assessed. Results and Discussion: The examination of SR granules and bilayer tablets revealed outstanding packing qualities and excellent flow properties, with bulk and tapped densities ranging from 0.39-0.46 g/cm³ and 0.42-0.55 g/cm³, respectively. In vitro dissolution tests revealed that the immediate-release layer gave an initial burst of Irbesartan. Still, the sustained-release layer of metformin showed controlled drug release over 12 hours at greater polymer concentrations. According to stability testing, the bilayer tablets' physical properties, drug content, and dissolving profiles did not change significantly. Conclusion: The bilayer tablet combination of Irbesartan and Metformin exhibited desired physical features, controlled drug release, and stability. This formulation represents a viable treatment option for diabetic hypertensive patients, offering effective and consistent management of both disorders while improving patient compliance.

Quality by design-based development and in vitro evaluation of dual release tablet of etoricoxib and thiocolchicoside: A novel chronotherapeutic approach for arthritis pain management

The traditional drug delivery system is not much effective when treating chronopathological diseases like arthritis. Consequently, there is a gap in the market for a delivery system that can provide an explicit treatment following the chronopharmacology of this disorder. The present study is based on the objective to develop Eudragit coated dual release bilayer tablet designed by the quality by design (QbD) and based on the chronotherapeutic approach. The dual release tablet contained an immediate release layer of etoricoxib and a sustained release layer of thiocolchicoside. The quality target product profile (QTTP) of the formulation was established along with critical quality attributes (CQA). The optimization of the dual release layer was done using a three-level, three-factor Box-Behnken design. A total of thirteen formulations of etoricoxib (ET1-ET13) and thiocolchicoside (TH1-TH13) were developed based on the design composition of etoricoxib, sodium starch glycolate and sodium bicarbonate for the immediate release (IR) layer and thiocolchicoside, HPMC E5 LV and magnesium stearate for the sustained release (SR) layer respectively. The developed dual release layers were compressed to form a bilayer tablet. The bilayer tablets were further coated with pH-dependent polymer Eudragit S-100 to avoid drug release in upper GIT. The initial characterization and drug-excipient interaction studies were performed initially using infra-red (IR) spectroscopy and X-ray diffraction studies (XRD). Formulations showing good micrometric properties, disintegration and drug release were selected for final compression of bilayer tablets. Formulation ET13 showed the fastest drug release (88%) at 15minutes and quick disintegration time (21s). The sustained release thiocolchicoside tablet layer (TH1-TH13) had a hardness that varied from 4.01 to 4.45kg/cm2. Formulation TH12 had the highest hardness, whereas TH6 showed the lowest hardness. The sustained release layer showing 97.63% of drug release after 8hours was selected for the compression to bilayer tablet. The developed dual layer tablets were investigated for quality parameters like hardness, percentage friability, weight variation, disintegration and dissolution. A high level of patient compliance is ensured through the current design as the patient does not need to get out of bed at night to take the medication.

Tandem Queue and Its Applications in the Production of Bi-layer Tablets

Tandem Queue and Its Applications in the Production of Bi-layer Tablets

Design and evaluation of oseltamivir phosphate dual-phase extended-release tablets for the treatment of influenza

In this study, once-daily extended-release tablets with dual-phase release of oseltamivir phosphate were developed for the treatment of influenza. The goal was to improve patient adherence and offer more therapeutic choices. The tablets were manufactured using wet granulation, bilayer tablet compression, and enteric membrane-controlled coating processes. Various polymers, such as hydroxypropyl methylcellulose (HPMC K100MCR, K15MCR, K4MCR, K100LV), enteric polymers (HPMC AS-LF, Eudragit L100-55) and membrane-controlled polymers (OPADRY® CA), were used either individually or in combination with other common excipients. The formulations include enteric-coated extended-release tablet (F1), hydrophilic matrix extended-release tablet (F2), semipermeable membrane-controlled release tablet (F3) and a combination extended-release tablet containing both enteric and hydrophilic matrix (F4). The in vitro drug release profile of each formulation was fitted to the first-order model, and the Ritger-Peppas model suggested that Fickian diffusion was the primary mechanism for drug release. Comparative bioequivalence studies with Tamiflu® (oseltamivir phosphate) capsules revealed that formulations F1, F2, and F3 did not achieve bioequivalence. However, under fed conditions, formulation F4 achieved bioequivalence with a relative bioavailability of 95.30% (90% CI, 88.83%-102.15%). This suggests that the formulation F4 tablet could potentially be a new treatment option for patients with influenza.

Formulation and evaluation of floating bilayer tablet of Aceclofenac and Esomeprazole

Formulation and evaluation of floating bilayer tablet of Aceclofenac and Esomeprazole

Formulation and Evaluation of Bi-Layered Tablet of Divalproex Sodium

Formulation and Evaluation of Bi-Layered Tablet of Divalproex Sodium

Chitosan-based buccal mucoadhesive bilayer tablets enhance the bioavailability of tizanidine hydrochloride by bypassing the first-pass metabolism

Tizanidine hydrochloride (TZN) is an antimuscarinic agent used in the treatment of pain-related spasms, multiple sclerosis, and stroke-related spasticity. It has low oral bioavailability (40 %) due to excessive first-pass metabolism in the liver. The aim of this project was to enhance the systemic bioavailability of TZN by developing buccal mucoadhesive bilayer tablet formulations using chitosan salts with molecular weights of 136 kDa (7 cP) and 169 kDa (10 cP). Structural characterisation of chitosans and their salts was performed by FTIR, 1H NMR, DSC, TGA, and XRD analyses. Soluble chitosan salts, chitosan glutamate and chitosan chloride, for the adhesive layer, and insoluble ethyl cellulose for the impermeable backing layer were selected as polymers to fabricate the buccal tablets by direct compression method. The tablets containing TZN demonstrated high swelling and good mucoadhesion characteristics as well as released all the drug within 8 h. While TC10, formulated with 10 cP chitosan chloride, showed the highest swelling properties, TG10, prepared with 10 cP chitosan glutamate, exhibited the highest mucoadhesion. Chitosan glutamate tablets (TG7 and TG10) demonstrated better mucoadhesive characteristics and stability than chitosan chloride ones (TC7 and TC10) in the buccal medium based on the results of swelling and drug release studies. The permeability studies performed by Franz diffusion cell demonstrated that the amount of TZN passing through the bovine buccal mucosa was between 13.4 and 14.4 %. Stability studies conducted at 5 ± 2 °C, 25 ± 2 °C and 40 ± 2 °C for 6 months showed that no changes in the content uniformity and pH were observed. The in vivo comparative bioavailability studies in female New Zealand rabbits were performed and TZN-containing buccal mucoadhesive bilayer tablets fabricated with both chloride (TC10) and glutamate (TG10) salts of chitosan demonstrated three times higher bioavailability than the commercial TZN product (Sirdalud® oral tablet) administered by the gastrointestinal route.

Optimization and evaluation of bilayer tablet of probenecid

The main objective of my research work is to develop a bilayer tablet of Probenecid, in which one layer is immediate layer for immediate action and second layer is the sustain release layer for maintaining the dose of the drug. Probenecid is frequently administered up to 3 times in a day. So, the reducing dosing frequency by sustained release tablet.

IN VIVO EVALUATION OF OPTIMIZED FORMULATION OF DAPAGLIFLOZIN AND SAXAGLIPTIN BILAYERED TABLETS

Combining dapagliflozin and saxagliptin presents a promising strategy for managing type 2 diabetes mellitus by leveraging their distinct, yet complementary, mechanisms of action. A novel bilayer tablet with a 5 mg sustained release layer of saxagliptin and a 10 mg immediate release layer of dapagliflozin was developed. Live animal studies (in vivo) were conducted on rabbits to evaluate the effects of an optimized formulation. Based on in vivo performance, the novel bilayer tablets demonstrated greater bioavailability. A new, easy-to-use technique was created to simultaneously measure the two drugs (dapagliflozin and saxagliptin) in rabbit blood plasma. Evaluation of the technique’s parameters were done on rabbit plasma in accordance with ICH guidelines. The parameters for pharmacokinetic analysis were (AUC0-∞), (Cmax), Tmax and others. Direct calculations of the Cmax and Tmax were made using experimental plasma concentration versus time data. The AUC0-∞ was produced by adding the computed AUC0-24h using the trapezoidal rule. Using sample analysis of variance or independent sample t tests, average data variation was compared (one way analysis of variance). Statistical significance (p=0.05) was assessed using a 95% confidence interval.

Design, Development and Evaluation of Bilayer Tablet for Antihypertension Activity

Design, Development and Evaluation of Bilayer Tablet for Antihypertension Activity

FORMULATION AND EVALUATION OF MODIFIED PULSATILE CAPSULE FOR CHRONOPHARMACOTHERAPY OF RHEUMATOID ARTHRITIC PAIN

Objective: The objective of the present study was to design and evaluate pulsincap system for chrono pharmacotherapy of rheumatoid arthritis that combines advantages of both immediate and sustained release technology with the suitable delay of drug release. Methods: Pulsatile drug delivery system based on pulsincap® technology was designed using mucoadhesive microspheres and Tramadol bilayer tablet plugs. The drug-excipient interaction was carried out by FTIR. Hardness, thickness, lag time, and swelling index all play a role in optimizing tablet plugs. The microspheres were examined for parameters such as particle size, surface morphology, encapsulation efficiency, swelling index, % mucoadhesion, and in vitro dissolution. Results: In modified pulsincaps, bilayer tablet plug shows drug release within 40 min and hydrogel plugs shows good swelling index and suitable lag time. In microspheres formulations, MF9 is the most suitable among them as it shows better drug content, particle size, surface morphology, in vitro drug release, and release kinetics. The drug is released right away, followed by the dissolution of the enteric coating at pH 6.8, followed by a suitable delay of 6 hours, and then the maximum amount of drug release is 99.62% at the end of 10th h. Conclusion: The pulsatile delivery system developed with HPMCK4M and tamarindus gum as plugging material showed a satisfactory lag period when compared to Tamarindus gum alone. Drug release can be achieved from treated gelatin capsule and hydrogel plug for a prolonged period by MF9 formulation.

Recent Innovation in Manufacturing Bi-layer Tablet Technologies: An Emerging Trends Overview

Bi-layer tablet technologies is an upgraded advantageous technology that overcomes the disadvantages of the single - layer tablet. The development of pre-determined active ingredient sustained release and the inclusion of incompatible active pharmaceutical ingredients into a single unit dosage form have both been made possible through the availability of bi layer tablets to the pharmaceutical industry. One of the key design strategies for combining incompatible drugs with various indications and the same drug with a varying release rate is provided by bi layer tablets. A bi-layer tablet is appropriate for the combination of sequential release of two drugs as well as Sustained release of a tablet, wherein the first layer is for Immediate release as a loading dosage and the second layer is a maintenance dose. The best choice for drugs with low bioavailability and brief plasma half-lives is to formulate them as bi layer tablets for sustained release. Bi-layer tablets may be the best alternative to prevent physical separation from developing chemical incompatibilities across APIs and to allow for the development of many different profiles for drug release. Bi-layer tablets are currently being developed by several pharmaceutical companies for a variety of purposes, including patent extension, therapeutic use, and marketing, to name a few. As a result, the use of bi-layer tablet for analgesic, anti-inflammatory, and antihypertensive drugs is significantly different. To develop an innovative bi-layer tablet, a comprehensive mechanistic understanding must be developed through the use of dependable, analytical methods for risk management.

Evaluation of the Ejection Pressure for Tracking Internal Cracks during Compaction in Bilayer Tablet Formulations Using Experimental and Finite Element Methods.

This study aimed to evaluate the ejection pressure and the correlation of the findings with the occurrence of internal cracks within bilayer tablets (BLTs) consisting of metformin HCl (MF) and evogliptin tartrate (EG). Then, the mechanism of tablet failure was provided by the finite element method (FEM). The ejection pressure and the difference in diameter depending on MAIN-P were evaluated to understand the correlation between ejection pressure and change in the BLT internal structure. The ejection pressure and the difference in diameter increased as the MAIN-P increased, then steeply decreased from 350 MPa to 375 MPa of MAIN-P, despite there being no pattern in compaction breaking force and porosity. The mechanical integrity at the BLT interface was weakened by internal cracks, reducing ejection pressure. The stress distribution analysis during the compression revealed that crack formation caused by entrapped air located at the center of the BLT interface may not propagate due to concentrated stress, which promotes a tight bond at the edge of the BLT. Furthermore, complete delamination can occur in the ejection process due to localized and intensive shear stresses at the BLT interface. These findings indicate that the mechanisms of internal cracking and delamination were successfully confirmed by FEM simulation. Moreover, measuring ejection pressure before BLT manufacturing can prevent invisible tablet cracks without damaging the tablets.

Formulation and Development of Novel Sulfasalazine Bilayer Tablets for The Treatment of Arthritis Associated With IBD: In-vitro and In-vivo Investigations

Sulfasalazine needs frequent daily dosing and the administration of numerous tablets per day pose challenges to patient compliance, contributing to increased adverse effects and difficulties in disease control. These inconveniences result in less effective treatment for arthritis associated with inflammatory bowel disease i.e. ulcerative colitis etc. To improve drug bioavailability, a delayed-release mechanism that releases the drug at the colon is necessary. To develop and optimize colon-targeted controlled release bilayer tablets coated with pH-dependent polymers. The bilayer tablets containing the immediate release part and sustained release part were developed. The tablets were coated with enteric-coated with Eudragit® S-100 and l-100 to achieve release in the colon. Granule properties and tablets were evaluated. The physicochemical parameters of the tablets were evaluated including, stability study, and drug release in 0.1 N HCl (pH 1.2), pH 6.8 phosphate buffer, pH 7.4 phosphate buffer for 2, 1, and up to 24 h respectively. Radiographic imaging and in vivo pharmacokinetic studies were also done in Rabbits. The bilayer tablets containing immediate and sustained release were successfully developed for the colon targeting. The granule properties were found within the acceptable range indicating good flow properties. The physicochemical properties of the tablets were also found acceptable. The tablets did not show release in 0.1 N HCl and 6.8 phosphate buffer but drug release was found under control in the 7.4 pH buffer. Sulfasalazine coated bilayer tablets were found stable and no significant changes were observed in the stability studies. Based on the X-ray studies, the formulated tablet remained discernible in the stomach, small intestine, and colon for a duration of up to 24 h. Finally, by the 32nd hour, the tablet was no longer visible in the X-ray examination, leading to the conclusion of complete drug release. The drug concentration in plasma remained within the therapeutic range for up to 24 h in vivo. These novel formulations present substantial advantages, providing prolonged targeted drug release and reducing systemic adverse effects. The results suggest promising potential for treating arthritis in Inflammatory bowel disease (IBD) patients, offering a solution to current delivery systems.

Recent Advances on Bilayer Tablet

When the high cardiac output exerts pressure on the arterial wall as blood flow increases, hypertension, or high blood pressure, occurs. Bi-layer tablets consists with one layer of the drug prepared for immediate release or a second layer intended for sustained release, these can be used as an sustained release method or as a second dose. A bi-layered tablet is used to break away two chemicals that are incompatible, release both drugs continually in combination, or create a sustained release tablet with an initial dose that is released immediately and a maintenance dose that is granted as with time. Bilayer tablets can be used for sustained release tablets, where the first layer is immediate release as the initial dose and the second layer is delayed release. It can also be used for the sequential release of two drugs combination or at separate two incompatible items.

A Comprehensive Review on Floating Drug Delivery System

The category of gastroretentive drug delivery systems (GRDDS) includes floating drug delivery systems (FDDS). These dose formulations are intended to extend the duration of the stomach's residence period by a sustained release technique. Drugs which are harder to dissolve in high pH environments have improved bioavailability and solubility when incorporated into GRDDS. Reduced intestinal absorption of solid dose forms can be accomplished by the flotation mechanism. The novel fusion of bilayer and floating mechanism is demonstrated by the bilayer floating drug delivery device. It demonstrates the effective creation of a controlled release formulation. Bilayer floating tablets offer a sustained release layer formulation in addition to an immediate release. A attempt was made to explain the mechanism of FDDS, or floating bilayer, in the review. In order to accomplish regulated administration of various medications with predetermined release profiles, bi-layer tablets were developed. The pharmaceutical industry has been more interested in creating bilayer tablets over the past ten years as a way to improve patient compliance and convenience by combining two or more API in a single dose form.

A unique composite bilayer tablet composed of porous organic frameworks and two kinds of green solvents for adsorption of fluoroquinolone antibiotics and anionic pigments from water

Due to convenient use, adjustable composition and easy preparation, sorbent tablets are considered to have obvious characteristics in the field of separation, especially for water environmental pollutants. In this study, the green, facile and catalyst-free way was employed to synthesize deep eutectic solvent and ionic liquid@porous organic frameworks (DES@POF and IL@POF), which showed specific surface area and stability; and their adsorption capacities were 187.74 (ciprofloxacin) and 111.28 mg/g (carmine), respectively. Then the two complexes were mixed with diluent and pressed to become monolayer and bilayer composite tablets; especially, the latter had two sides like a coin, which were based on DES@POF and IL@POF, respectively. During the following studies, the tablets exhibited satisfied continuous working ability and adsorption efficiency (99.57% as the highest) for the selected antibiotics and pigments. The key influential factors for their preparation and performance were investigated systematically, and separation mechanisms as well as selectivity were also discovered. The whole process was well fitted by the Langmuir isotherm model and quasi second-order kinetic model. Such a kind of sorbent tablets can be reused and renewed, which can provide useful reference on the development for new forms of separation mediums.