Formulation, Development and Evaluation of Bilayer Floating Tablets of Antihypertensive Drug Bosentan

Hypertension, or high blood pressure, is a major public health concern around the world because of its large contribution to the global health burden and its function as a major risk factor for a variety of disease processes. Bosentan SR Floating Bilayer Tablets were made with HPMC K4M, HPMC E-15, and HPMC E-15 alone (80%) and in combination with varying percentages of polymer (20&60 percent, 40&40 percent, and 60&20 percent ). The hydrophilic polymer HPMC is used to make three different formulations (M4, M8, and M12) of floating Bosentan SR tablets, each with a viscosity grade of 80 percent. M12 formulation was shown to be suitable for SR tablet formulation. From the M12 formulation. It's based on the M12 formula. The fraction of high viscosity polymer can be lowered by adding low viscosity polymer, as demonstrated in the C3 formulation. It was clear from the dissolution profile of formulation C3 that by mixing the low and high viscosity polymers, the drug release from the formulation may be improved as compared to manufacturing M12 high viscosity polymer alone. According to the findings of this investigation, as floating duration increases, the release rate drops. As a result, it's appropriate for long-term formulation. Keywords: Bosentan, Floating Bilayer Tablets, Hypertension, SR Tablets, HPMC K4M, E-15

Development of a Robust Control Strategy for Fixed-Dose Combination Bilayer Tablets with Integrated Quality by Design, Statistical, and Process Analytical Technology Approach

Control strategy and quality by design (QbD) are widely used to develop pharmaceutical products and improve drug quality; however, studies on fixed-dose combination (FDC) bilayer tablets are limited. In this study, the bilayer tablet consisted of high-dose metformin HCl in a sustained-release layer and low-dose dapagliflozin l-proline in an immediate-release layer. The formulation and process of each layer were optimized using the QbD approach. A d-optimal mixture design and response surface design were applied to optimize critical material attributes and critical process parameters, respectively. The robust design space was developed using Monte Carlo simulations by evaluating the risk of uncertainty in the model predictions. Multivariate analysis showed that there were significant correlations among impeller speed, massing time, granule bulk density, and dissolution in the metformin HCl layer, and among roller pressure, ribbon density, and dissolution in the dapagliflozin l-proline layer. Process analytical technology (PAT) was used with in–line transmittance near-infrared spectroscopy to confirm the bulk and ribbon densities of the optimized bilayer tablet. Moreover, the in vitro drug release and in vivo pharmacokinetic studies showed that the optimized test drug was bioequivalent to the reference drug. This study suggested that integrated QbD, statistical, and PAT approaches can develop a robust control strategy for FDC bilayer tablets by implementing real-time release testing based on the relationships among various variables.

FORMULATION AND EVALUATION OF METFORMIN HYDROCHLORIDE AND GLICLAZIDE SUSTAINED RELEASE BILAYER TABLETS: A COMBINATION THERAPY IN MANAGEMENT OF DIABETES

Objective: The main objective of the present investigation is to develop a sustained-release (SR) formulation to optimize the postprandial elevation of glucose level in type 2 Diabetic subjects using combination therapy. In the present research work, bilayer sustained release formulation of metformin hydrochloride (MFH) and gliclazide (GLZ), based on monolithic-matrix technology was developed and evaluated. Methods: The formulations of metformin hydrochloride layer and gliclazide layer that contain polyox WSR coagulant and different viscosity grades of hydroxyl propyl methylcellulose (HPMC) as sustained-release matrix were prepared by direct compression and wet granulation method respectively. The bilayer tablets were prepared after carrying out the optimization of metformin layer and evaluated for various pre-compression and post-compression parameters. For the best formulation selected on basis of in vitro evaluation of tablets, Fourier-transform infrared spectroscopy (FT-IR) studies and comparison of in vitro dissolution profile of developed formulation with the innovator were performed. Results: Metformin hydrochloride and gliclazide showed sustained release of drug by diffusion mechanism and followed first-order kinetics. The best formulation of metformin hydrochloride (M7) and gliclazide (G8) show 99.93% and 99.65% of drug release in 24 h respectively. The similarity factor (f2) was 79.95 for metformin hydrochloride and 73.62 for gliclazide when compared with the innovator. Conclusion: The monolith diffusion-controlled bilayer tablets of metformin hydrochloride and gliclazide offer improved patient compliance and convenience with better postprandial hyperglycemic control with once-a-day dosing. The sustained release of the drug up to 24 h regulate antidiabetic activity round the clock with minimal side effects.

A REVIEW OF CHALLENGES AND POSSIBILITIES OF BILAYER TABLET TECHNOLOGY

Bilayer tablet making process involves certain challenges as well as advantages. Bilayer tablets are the prescriptions which comprise of two same or various medications consolidated in a solitary portion for viable treatment of the illness. Persistent consistence and cost measure are two significant boundaries in treatments. Bilayer tablets manage these focuses adequately. To deliver a decent quality bi-layer tablet, the apparatus should be built according to GMP. Different hardware are accessible to beat normal bi-layer issues, for example, layer detachment, lacking hardness, weight control, cross defilement between the layers and so forth. Bilayer tablets give one of the significant plan approaches where inconsistent medications, with an alternate sign, and same medication with various delivery rate can be combined in a solid unit. Bilayer tablet is reasonable for consecutive arrival of two medications in blend, and for supported delivery tablets in which one layer is promptly delivered as introductory portion and the subsequent layer is a controlled portion. Controlled delivery dose structures have been broadly used to improve treatment with a few significant medications. Utilization of bilayer tablet is an altogether different viewpoint for calming and pain relieving drugs. This review article clarifies what are the outcomes to be looked and how to be faced during bilayer tablet production.

A REVIEW ON AN EMERGIN TREND BILAYER FLOATING DRUG DELIVERY SYSTEM

NDDS is advanced drug delivery system which improves drug potency, control drug release to give a sustained therapeutic effect, provide greater safety, finally it is to target a drug specifically to a desired tissue. Novel drug delivery system have been developed to overcome the limitation of conventional drug delivery systems, such as of gastric retention by decreasing fluctuations in the concentration of the drug in blood,resulting in the reduction in unwanted toxicity and poor efficiency. As compared to traditional dosage forms bilayer tablets are more efficient for sequential release of two drugs that can be different or identical. Bilayer tablet is also capable of separating two incompatible substances and also for sustained release. Gastro retentive drug delivery system retains the period of dosage forms in the stomach or upper gastro intes-tinal tract ,as to improve bioavailability and the therapeutic efficacy of the drugs. Mainly the bilayer drug delivery system is suitable for drugs whose therapethic windows are narrow in the gastrointestinal tract (GIT) and also they have low elimination half life: 3-4 h. The purpose of this review is to disclose the challenges faced during the formulation of bilayer tablets. Finally, the whole article is firmly analyzed in a concluding paragraph. KEYWORDS: Conventional drug delivery systems, Bilayer tablet, Gastro retentive, Bioavailability

Formulation and In Vitro Evaluation of Bilayer Tablets of Lansoprazole and Amoxycillin Trihydrate for the Treatment of Peptic Ulcer

The present work involves the formulation development, optimization and In-vitro evaluation of bilayer tablet containing Lansoprazole in the immediate release layer and Amoxycillin in the sustained release layer, using sodium starch glycolate as a super disintegrant for the immediate release layer and the hydrophilic matrix HPMC K100M, hydrophobic matrix Ethyl cellulose are used in the sustained release layer. Bilayer tablet showed as initial burst effect to provide dose of immediate release layer Lansoprazole to control the acid secretion level and the sustained release of Amoxycillin for 24 hours. Immediate and sustained release tablets were formulated by wet granulation method because of the poor flow property of the blends. The prepared bilayer tablet was evaluated for their precompression parameters, physical characteristics like hardness, friability, uniformity of weight, uniformity of drug content, swelling index, In-vitro floating studies and In-vitro drug release. The release of the lansoprazole from the immediate release layer was found to be 97.46 ± 0.15% in 15minutes. The release of Amoxycillin Trihydrate for the sustained release floating layer was found to be 98.25 ± 0.14% in 12 hours. Lansoprazole potentiate the effect of Amoxycillin. Hence the bilayer tablets of Lansoprazole and Amoxycillin were used to improve patient compliance towards the effective management of ulcer. Keywords: bilayer tablet, Lansoprazole, and Amoxycillin, sustained release

Formulation and optimization of gastroretentive bilayer tablets of calcium carbonate using D-optimal mixture design

Gastroretentive bilayer tablets of calcium carbonate (CC) were developed using D-optimal mixture design. The effect of formulation factors such as levels of HPMC K100 M (X1), sodium bicarbonate (X2), and HPMC E15 LV (X3) on responses like floating lag time (R1) and release of CC at 1 h (R2) and 6 h (R3) was elucidated. The optimized formulations developed by numerical optimization technique were found to have short floating lag time (2.85 ± 0.98 min), minimum burst release (27.02 ± 1.18%), and controlled yet near complete release (88.98 ± 2.75%) at 6 h. In vivo radiographic studies in rabbits indicated that optimized batch displayed a mean gastric retention time (GRT) of 5.5 ± 1 h which was significantly prolonged (P < 0.05) compared to the conventional tablets that displayed a GRT of less than 1 h. The studies proved that the gastroretentive tablets can be a promising platform to improve bioavailability of nutrients having absorption window in upper gastrointestinal tract.

Analysis on the evaluation of aceclofenac bilayer tablets and its formulation using FT-IT method

The detached of the current research progress a bilayer tablet of aceclofenac utilizing sodium starch glycolate (SSG) and croscarmellose sodium (CCS) as super disintegrants for the formulation of immediate-release layer whereas polymers such as methocel K15M, Lubrizol 971P were utilized by the formulation of sustaining layer. The tablets were equipped by straight density technique. The organized tablets were estimated for pre-compressed parameters like micromeritic properties and post compressed parameters like bulk variation, aceclofenac satisfied and in-vitro dissolution studies. The in-vitro dissolution studies showed about 86.78 % of aceclofenac release from the bilayer tablet, indicating that a preliminary burst release of aceclofenac followed by sustaining action up to 12 h by the sustained layer of the tablets. In-Vitro kinetic data revealed that all the formulations surveyed the Higuchi prototype via fickian dispersal as announcement device subsequently the preliminary rupture announcement. FT-IR studies exposed here is no communication among the drug and polymers utilized in the study. The errand of medication is to safeguard and reestablish wellbeing and to soothe languishing. In this context, the most commonly used pain-relieving agent is aceclofenac an NSAID. In the present investigation, aceclofenac bilayer tablets were prepared to provide sustain effect for better therapeutic effect. These points of interest, clarify the requirement for the planning of changed medication conveyance framework.