Formulation Of 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 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.

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.

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.

Quality by design approach for the formulation of bilayer tablets of domperidone and itopride in gastro esophageal reflux disease

In the current work, a bilayer tablet of itopride gastroretentive and domperidone immediate release formulation was developed showing the synergistic effect of gastric motility in gastroesophageal reflux disease, through antidopaminergic and antiacetylcholine stearic activities. A bilayer tablet of domperidone and itopride was optimized using quality by design and its product performance was analyzed. Itopride was designed to be gastroretentive and remains in the stomach for a longer period, providing sustained release. The domperidone layer was optimized by an empirical hit and trial method, while the itopride layer was optimized using the Box Behnken experimental design. Three independent variables were considered as hydroxypropyl methyl cellulose K 100 M, xanthum gum, and Carbomer 974 with dependent variables like floating lag time, swellable index, and percentage drug release at 24 hours. Quality target product profile and critical quality attributes were studied which helps in an effective way to develop bilayer tablets. The excipients were chosen based on the time taken by medicaments to be released and the quantity was optimized according to Handbook of Pharmaceutical Excipient. From the optimization processes, DF5 and IH2 were selected as optimized composition for the formulation of domperidone and itopride layer of bilayer tablet respectively. The bilayer tablets were formulated in 16 × 8.26 mm oblong plain biconcave die and punch. The in-vitro drug release of domperidone was 99.39% in 30 minutes and itopride was 27.50%, 53.45%, and 93.65% at 4, 16, and 24 hours respectively.

Phase III study of bilayer sustained-release tramadol tablets in patients with cancer pain: a double-blind parallel-group, non-inferiority study with immediate-release tramadol capsules as an active comparator

PurposeWe investigated whether twice-daily administration of a bilayer tablet formulation of tramadol (35% immediate-release [IR] and 65% sustained-release) is as effective as four-times-daily IR tramadol capsules for managing cancer pain.MethodsThis randomized, double-blind, double-dummy, active-comparator, non-inferiority study enrolled opioid-naïve patients using non-steroidal anti-inflammatory drugs or acetaminophen (paracetamol) to manage cancer pain and self-reported pain (mean value over 3 days ≥ 25 mm on a 100-mm visual analog scale [VAS]). Patients were randomized to either bilayer tablets or IR capsules for 14 days. The starting dose was 100 mg/day and could be escalated to 300 mg/day. The primary endpoint was the change in VAS (averaged over 3 days) for pain at rest from baseline to end of treatment/discontinuation.ResultsOverall, 251 patients were randomized. The baseline mean VAS at rest was 47.67 mm (range: 25.6–82.7 mm). In the full analysis set, the adjusted mean change in VAS was − 22.07 and − 19.08 mm in the bilayer tablet (n = 124) and IR capsule (n = 120) groups, respectively. The adjusted mean difference was − 2.99 mm (95% confidence interval [CI] − 7.96 to 1.99 mm). The upper 95% CI was less than the predefined non-inferiority margin of 7.5 mm. Other efficacy outcomes were similar in both groups. Adverse events were reported for 97/126 (77.0%) and 101/125 (80.8%) patients in the bilayer tablet and IR capsule groups, respectively.ConclusionTwice-daily administration of bilayer tramadol tablets was as effective as four-times-daily administration of IR capsules regarding the improvement in pain VAS, with comparable safety outcomes.Clinical trial registrationJapicCTI-184143/jRCT2080224082 (October 5, 2018).

Development, Physicochemical Characteristics and Pharmacokinetics of a New Sustained-Release Bilayer Tablet Formulation of Tramadol with an Immediate-Release Component for Twice-Daily Administration.

There are some potential concerns about the currently marketed solid oral dosage forms of tramadol, including decreased adherence to immediate-release (IR) formulations due to the high number of doses taken each day and the slow rise in the blood tramadol concentration after administration of sustained-release (SR) formulations, which may not achieve a rapid analgesic effect. To overcome these potential concerns, a twice-daily double-layered tablet formulation of tramadol comprising IR and SR layers was developed. This article reports studies that assessed its physicochemical and pharmacokinetic properties. Dissolution tests of five bilayer tablet formulations (designated tablets A-E) and pharmacokinetic studies of tablets A and B were conducted to investigate the appropriate ratio of the IR/SR layers in the double-layered tablet. Additionally, pharmacokinetic studies of three finished dosage formulations (tablets C-E) were performed in healthy adult males to investigate the effect of food intake on drug absorption. Adjusting the excipients and tramadol content in the IR and SR layers of tablets A-E altered their dissolution profiles in a manner that could be predicted based on their compositions. The IR layer was released within 15min, and the SR layer was slowly released over 10h. In the pharmacokinetic study, the time to maximum plasma concentration (tmax) of tramadol after administration of tablets A (IR:SR: 20:80mg) and B (40:60mg) was shorter than that of a commercially available SR tablet, and the half-life (t1/2) was longer than that of a commercially available IR tablet. For tablets C-E, administration after food did not affect the area under theconcentration-time curve (AUC) or maximum drug concentration (Cmax) of tramadol, but the tmax was prolonged by about 1 h compared with administration in fasting conditions. The mean ± standard deviation tmax and t1/2 for tablet D (IR:SR: 35:65 mg) in the fasting condition was 1.09 ± 0.56h and 7.82 ± 0.85h, respectively. The respective values in the fed condition were 2.47 ± 1.06h and 7.12 ± 0.85h, respectively. To address the potential concerns regarding existing formulations of tramadol, a twice-daily, extended-release bilayer formulation of tramadol consisting of an IR and SR layer was developed. Pharmacokinetic studies confirmed that the plasma tramadol concentration increased quickly after administration and was maintained over a long period of time.

Development and validation of pharmaceutical oral formulation of bilayer tablet of sustained release and immediate release of gliclazide

Development and validation of pharmaceutical oral formulation of bilayer tablet of sustained release and immediate release of gliclazide

Controlled release of MT-1207 using a novel gastroretentive bilayer system comprised of hydrophilic and hydrophobic polymers

In the present study, novel gastroretentive bilayer tablets were developed that are promising for the once-a-day oral delivery of the drug candidate MT-1207. The gastroretentive layer consisted of a combination of hydrophilic and hydrophobic polymers, namely polyethylene oxide and Kollidon® SR. A factorial experiment was conducted, and the results revealed a non-effervescent gastroretentive layer that, unlike most gastroretentive layers reported in the literature, was easy to prepare, and provided immediate tablet buoyancy (mean floating lag time of 1.5 s) that lasted over 24 h in fasted state simulated gastric fluid (FaSSGF) pH 1.6, irrespective of the drug layer, thereby allowing a 24-hour sustained release of MT-1207 from the drug layer of the tablets. Furthermore, during in vitro buoyancy testing of the optimised bilayer tablets in media of different pH values (1.0, 3.0, 6.0), the significant difference (one-way ANOVA, p < 0.001) between the respective total floating times indicated that stomach pH effects on tablet buoyancy are important to be considered during the development of non-effervescent gastroretentive formulations and the choice of dosing regimen. To the best of our knowledge, this has not been reported before, and it should probably be factored in when designing dosing regimens. Finally, a pharmacokinetic study in Beagle dogs indicated a successful in vivo 24-hour sustained release of MT-1207 from the optimised gastroretentive bilayer tablet formulations with the drug plasma concentration remaining above the estimated minimum effective concentration of 1 ng/mL at the 24-hour timepoint and also demonstrated the gastroretentive capabilities of the hydrophilic and hydrophobic polymer combination. The optimised formulations will be forwarded to clinical development.

Pharmacokinetic Evaluation of Telmisartan and Cilnidipine Bilayer Tablet in A Rabbit Model

Hypertension is a chronic medical condition affecting a significant proportion of the global population. It is a major risk factor for cardiovascular diseases, stroke, and kidney failure. Telmisartan and cilnidipine combination are commonly used in managing hypertension due to their complementary mechanism of action. Therefore, a bilayer tablet design that enhances the pharmacokinetic profile of cilnidipine as a sustained-release drug while telmisartan act as an immediate-release drug may provide a better therapeutic option for hypertension management. We aim to evaluate the pharmacokinetic parameters of the bilayer tablet of Telmisartan and Cilnidipine. Our objective is to observe the bioavailability of the bilayer tablet in rabbit plasma. The formulation aims to achieve an immediate release effect for Telmisartan and a sustained release effect for Cilnidipine. The solubility and bioavailability of Telmisartan were enhanced by complexation with beta-cyclodextrin. To achieve our aim, we observe the drug concentration in rabbit plasma. Telmisartan is an angiotensin receptor blocker, while Cilnidipine is a calcium channel blocker. The pharmacokinetics of the drugs were evaluated in New Zealand rabbits following oral administration. Systemic drug bioavailability was assessed, and an HPLC method was developed to estimate Telmisartan and Cilnidipine's plasma concentration simultaneously. A Gemini C-18 column (250 mm X 4.6 mm X 5 microns) Phenomenex was used for peak separation. The mobile phase consisted of acetonitrile with phosphate buffer pH 3.5 v/v, with a flow rate of 1.5 ml per minute. The calibration curve analysis indicated a correlation coefficient of 0.9996 and 0.9997 for Telmisartan and Cilnidipine, respectively. The pharmacokinetics of the optimized batch, including Cmax, Tmax, and AUC values, were compared to those of the pure drug. Drug concentration was detected using a DAD detector with an excitation wavelength of 241nm. No interaction was observed between the drugs and excipients. The in-vivo study of the formulation showed higher bioavailability, indicating that the developed bilayer tablet formulation could be an effective means of delivering Telmisartan and Cilnidipine.

Formulation and Evaluation of Bi-Layer Tablet of Nebivolol and Nateglinide

In the present work, the Bilayered matrix type tablet were prepared by direct and wet granulation technique, in which immediate release layer ( by direct compression) contains Nebivolol and extended release layer (by wet granulation) contains Nateglinide. All the developed bilayer tablets were evaluated for weight variation, friability, thickness and hardness. The percent deviation from the average weight, friability, thickness and hardness was found to be within the prescribed official limits. Release profile of Nebivolol from formulations indicate that lower MCC (Formulations CF1 and CF3) and lactose (Formulation CF3) content displayed higher release rates as compared to formulation with higher MCC and lactose content (Formulation CF2). Also the concentration of KYRON T-314 is also found to influence the release rate of the drug. It was found that formulation containing the highest concentration of superdisintegrants (Formulation CF3) has grater release then other subsequent formulations (Formulations CF1 and CF3). Similarly, the release profile of Nateglinide from formulations indicate that lower HPMC K15M (Formulation CF3) and lactose (Formulation CF3) content displayed higher release rates as compared to formulation with individual HPMC K15M, HPMC K100M, EC (Formulations CF1 and CF2) and higher lactose content (Formulations CF1 and CF2).

A Study on Bilayer Tablets for the Anti-Allergic Drug

The bilayer tablet formulations used for each individual layer should be compressible (i.e., the capacity of a material to undergo a reduction in volume as a result of an applied pressure) and compactable (i.e., the capacity of a powder to be transformed into tablets with strength during densification) on their own, i.e., they should show satisfactory reduction in volume and form mechanically sound and coherent solid bodies. A bigger contact area exists between the layers as a result of the increased surface roughness, which improves interlayer adhesion. Bilayer tablet characterisation in early formulation development has certain advantages, including Bilayer tablet interfacial strength should be quantified, unusual or extreme properties of compacted layers should be identified, lot-to-lot consistency of the produced tablets should be ensured, rational formulation development strategy followed, material failure mechanisms during tablet manufacturing should be explained, and tablet-specific factors' effects should be understood.

Formulation of Modified-Release Bilayer Tablets of Atorvastatin and Ezetimibe: An In-Vitro and In-Vivo Analysis.

The objective of this work was to formulate co-loaded bilayer tablets containing ezetimibe (EZB) and atorvastatin (ATC). ATC loaded in the immediate-release (IR) layer is an HMG CoA reductase inhibitor, while EZB, added in the sustained-release (SR) layer, is a lipid-lowering agent. This study was conducted to evaluate the effects of polymer on the formulation and characterization of bilayer tablets, as well as the therapeutic impact of the concurrent use of both drugs having a sequential release pattern. To obtain the optimized results, four different formulations with variable compositions were developed and evaluated for different parameters. The drug release studies were carried out using a type II dissolution apparatus, using phosphate buffer solution (PBS) of 1.2 pH for IR of EZB for an initial 2 h, followed by 24 h studies for ATC in PBS 6.8 pH. The IR layer showed rapid drug release (96%) in 2 h, while 80% of the ATC was released in 24 h from the SR layer. Locally obtained, 6-week-old female albino rats were selected for in vivo studies. Both preventive and curative models were applied to check the effects of the drug combination on the lipid profile, atherosclerosis and physiology of different organs. Studies have shown that the administration of both drugs with different release patterns has a better therapeutic effect (p < 0.05), both in preventing and in curing hyperlipidemia. Conclusively, through the sequential release of ATC and EZB, a better therapeutic response could be obtained.

Formulation and evaluation sustained and immediate release bilayer tablet of telmisartan and amlodipine

The study was undertaken with the aim to Formulation and evaluation of bilayer tablet formulation of Telmisartan and Amlodipine. Thus, from the results, it is concluded that the formulation of immediate release layer of Amlodipine using 4-2% concentration of Crospovidone &amp; PVA K30 and 30-20-1.5% concentration of HPMC K 100M-HPMC K4 M-HPMC K15 M are considered as ideal for optimized bilayer tablet formulation. The drug release data of the Telmisartan and Amlodipine was fitted into various kinetic models which as shown in figures 3.8 and 3.11. The order of release of drug was found to be zero order, in which R2 value was close to 1. The n value of Korsmeyer Peppas equation was found to be 0.746. Good correlation coefficients are obtained for Higuchi equation. The results showed that the formulation followed Peppas Model release. Thus, this optimized bilayer tablet formulation can be successfully used in the treatment of hypertension. This modified release bilayer tablets also reduced dosing frequency, increase the bioavailability and provide better patient compliance. From the results it was found that formulation F4 was the best formulation amongst the 5 formulations.

Formulation and Evaluation of Bilayer Tablet of Saxagliptin

In the present study Saxagliptin 60mg tablets have been formulated and developed using direct compression and dry granulation technique, to provide a safe, highly effective method for treating congestive heart failure, edema and kidney disorder, while reducing undesirable adverse effects. Pre and post formulation parameters were studied for the formulated batches. The result of all the physical and in-vitro dissolution data concluded that bilayer tablet (I3,S9) was the most promising formulation. The trial conducted with the consecutive three batches for immediate release and sustained release revealed relative standard deviation below 2 %, indicative the insignificant batch-to-batch variation that can be overcome if processes are run out in a controlled manner. Using Crosspovidone as super disintegrate and HPMC as sustained release polymer blend would be cost effective and dissolution mediums 0.1N HCl would the ideal media for conducting dissolution studies. It was concluded that the bilayer tablet formulation can be act as a better tool for the successful administration of two or more drug which will remain stable for longer period of time.

Compatability study of selexipag and ezetimibe with selected excipients in formulation of bilayer tablet

Present study was carried out to study compatibility of Selexipag and Ezetimibe with selected generally regarded as safe excipients and to prepare bilayer tablet. Isothermal stress testing was performed in binary a mixture which was subjected to 50°C for 4 weeks. Isothermal stressed samples were evaluated with RP-HPLC method and FTIR analysis. A trial was conducted with single disintegrants and diluent with direct compression technique and in-vitro dissolution was carried out. To improve the release profile of Immediate Release layer of Selexipag, multiple disintegrants were used namely croscarmellose sodium (CCS), sodium starch glycolate (SSG) and Crospovidone (CP). Similarly, extended release layer of Ezetimibe was prepared by wet granulation technique. Intra and extra granulation was done with mixtures of disintegrants. Extended release layer of Ezetimibe was formulated using polymers and gums like HPMC, MCC, PVP, Talc, Gaur gum, and Xanthan gum, Magnesium stearate. The results show that Selexipag and Ezetimibe were compatible with the all the polymers used in the study. The polymers used in the present study and the formulations developed using the compatible excipients were found to be stable.

Formulation and evaluation of selexipag and ezetimibe bi-layer tablet by novel approach

Hypertension and hypercholesterolemia are two common diseases that often coexist. The combined presence of hypertension and hypercholesterolemia increases considerably the risk for cardiovascular complications. Selexipag is used to treat symptoms of pulmonary arterial hypertension and Ezetimibe is a lipid-lowering compound that inhibits intestinal cholesterol and phytosterols absorption. The bilayer tablets of antilipidemic and antihypertensive can be employed for the treatment of hypertension and hypercholesterolemia together through oral administration of single tablet. The rationale for this fixed-dose combination is to co-administer two drugs acting by different mechanisms of action together, reduce dosing frequency, and increase patient compliance. In the present investigation we combine Selexipag and Ezetimibe. Immediate release layer of Selexipag was formulated using various superdisintegrants like Crospovidone, Croscarmellose sodium, and sodium starch glycolate, Microcrystalline Cellulose, Magnesium Stearate and Extended release layer of Ezetimibe was formulated using polymers and gums like Hydroxy Propyl methyl cellulose, Poly vinyl Pyrrolidone, Talc, Gaur gum, and Xanthan gum, Magnesium stearate. The disintegration and dissolution study of both layers showed that inclusion of surfactant to the tablet formulation (Immediate Release) and dissolution medium (Extended Release) enhanced the release of drugs from both layers.

Formulation and Evaluation of Sustained Release Bilayer Matrix Tablet of Glimepiride and Metformin Hydrochloride

The aim of the present study was to design and evaluate bilayer tablets of metformin hydrochloride as sustained release form for the treatment of Type-II diabetes mellitus. The basic aim of any Bi-layer tablet formulation is to separate physically or chemically incompatible ingredients and to produce repeat action or prolonged action of tablet. They are many drugs for treating type-II diabetes. Sulphonyl urea and biguanides are used commonly by a wide section of patients. Melt granulation process was used for the formulation of sustained comprising metformin layer and wet granulation of immediate comprising layer of glimepiride. The precompression studies like bulk density, tapped density, angle of repose, compressible index and post formulation studies includes weight variation, hardness, thickness, friability and dissolution study. The in-vitro release profile of Glimepiride was dissolved within 45 min, and Metformin Hydrochloride was able to release more than 12 hrs. They all the formulation was optimized formula due to its higher rate of dissolution and collate all other parameters with the official specifications.

FIXED-DOSE COMBINATION DRUGS AS TABLET IN TABLET: A REVIEW

The Pharmaceutical industry has become more interested in developing fixed-dose combinations (FDCs) in recent years. FDCs have been used successfully in a variety of clinical areas, including diabetes, HIV/AIDS,and cardiovascular diseases etc. FDCs are intended to extend the product life cycle and enhance patient compliance by decreasing cost. Active Pharmaceutical ingredients are chosen for FDC development based on variety of purposes such as Pharmacokinetic profile, drug-drug interactions, mechanism of action, and manufacturability for successful development. Tablet in tablet technology has gained popularity in recent years for creating modified release products. The compression coating or solvent-free-coating technology is also known as Tablet in Tablet technology. Tablet in Tablet technology is presently the finest alternative technology for the formulation of bilayer tablets for physical separation of active medicines and used to avoid chemical incompatibilities and to produce different drug release patterns such as rapid release, sustained release, controlled release, delayed release, and pulsatile release. This review mainly focuses on combining the techniques of both FDC and Tablet in Tablet formulations which offer a wide variety of benefits such as increased patient compliance, convenience, separation of incompatible ingredients, avoiding close interaction of two drugs, achieving various drug release patterns and maximizing the potency of both drugs over conventional oral dosage forms Keywords: Fixed dose combinations, Tablet in tablet technology, Compression coated tablet, Bilayer tablet, delayed release