Formulation and simultaneous estimation of sustained release bilayer tablet containing polythiazide and reserpine

The present research work was carried out to Formulate and evaluation of bilayer tablet dosage form for the treatment of Hypertension.The objective of this study to compare the specific characteristics of Metoprolol [beta selective (cardio selective) adrenoreceptor blocking agent] and Hydrochlorothiazide (Thiazide Diuretics]) in order to design stable formulation. It can be concluded that bilayer tablet were successfully formulated to achieve immediate release of Hydrochlorothiazide (HCTZ) and tailored release of Metoprolol (MPL)by using Dual Release Drug Absorption System(DUREDAS technology).Both drugs were found to be stable in Bilayer tablet formulation and were found to be stable for few months. This bilayer tablet dosage form increases the stability which may reduce loss and cost of formulation. It improves the benefits of producer, retailer, and patients. Recently, greater attention has been focused on development of bilayer tablet formulations. Over the past 30 years, the expenses and complications involved in marketing new drug entities have increased with concomitant recognition of therapeutic advantages of conventional drug delivery system. Several pharmaceutical companies are currently developing bi-layer tablets, for a variety of reasons: patent extension, efficient pharmacological effect, better patient compliance, etc. Bilayer tablet is becoming new approach for the successful drug delivery system and for better stability in combination. Bilayer tablets can be primary option to avoid chemical incompatibilities between APIs by physical separation.
 Keywords: Bilayer tablet, DUREDAS Technology, Antihypertensive, Metoprolol, Hydrochlorthiazide

From the previous work (Part I), mucoadhesive formulae containing 5% CP/65% HPMC/30% lactose and 2% PC/68% HPMC/30% mannitol as well as formulae based on sodium carboxymethyl cellulose (SCMC) were selected. Medicated tablets were prepared using diltiazem hydrochloride (DZ) and metclopramide hydrochloride (MP) in two different doses (30 and 60 mg). The effect of drug and dose on the mucoadhesive properties and in‐vitro drug release was evaluated. All formulae produced extended drug release (over 8 to 12 h). Polyacrylic acid based matrices (PAA) showed Fickian's diffusion release pattern for both drugs. SCMC ensured zero‐order release for DZ, which deviated to anomalous behavior in case of MP. Doubling the dose significantly reduced the bioadhesion strength (p < 0.05) with a slight improvement in drug release rate. The formulation of bilayer tablets containing drug‐free layer and medicated layer enhanced the drug release without affecting the bioadhesive performance. The bilayer tablet formulated with 2% PC/68% HPMC/30% mannitol (PC2) was selected for studying the in‐vivo metoclopramide release in four healthy volunteers. The tablet ensured controlled drug release for 12 h, in addition, good correlation (r = 0.9398) was observed between in‐vitro and in‐vivo data. The effect of ageing on selected formulae containing DZ and MP, respectively, was studied. Storage at 40°C and 75% relative humidity for 6 months didn't influence the mucoadhesive performance, however, an enhanced released rate was observed.

In this study, a bilayer tablet which combines Ibuprofen in a sustained-release layer and Vonoprazan in an immediate-release layer is designed and tested. In separate batches, three highly effective super-disintegrants - sodium starch glycolate, polyplasdone XL, and croscarmellose sodium - were utilised to formulate the IR layer at different concentration levels of 3%, 4%, and 5%. To ensure sustained drug release in accordance with USP guidelines, a combination of Ibuprofen and three hydrophilic matrix-forming polymers, namely HPMC K4M, HPMC K15M, and Hypromellose K100M CR Premium, was used at concentration levels of 15%, 20%, and 25% respectively, for the SR layer. The appearance, thickness, hardness, friability, drug content, weight uniformity, and in-vitro dissolution characteristics of the manufactured bilayer tablets have been evaluated. Formulation T9, containing 7.5 mg of croscarmellose sodium, produced outstanding results among the IR batches, achieving a 99.25% release of Vonoprazan within a 0.1 N HCl solution after a short period of just one hour. The batch containing 325 mg of Hypromellose K100M CR Premium showed the most successful sustained release in the SR layer, outperforming other studied formulations by releasing 99.12% of Ibuprofen over 12 hours, first in 0.1 N HCl for 2 hours and then in phosphate buffer with a pH of 7.2.

Migraine is a chronic neurological disorder characterized by recurrent moderate to severe headaches often in association with a number of autonomic nervous system symptoms.The word derives from the Greek ἡμικρανία (hemikrania), "pain on one side of the head", from ἡμι-(hemi-), "half", and κρανίον (kranion), "skull".Typically the headache affects one half of the head, is pulsating in nature, and lasts from 2 to 72 hours.That affects approximately 17% of adult women and 6% of adult men.It is most common among people age 25 to 55, though it can affect children and teens as well.Migraine is about three times more prevalent in women than men; roughly one in five women and one in 16 men suffer from migraine Associated symptoms may include nausea, vomiting, and sensitivity to light, sound, or smell.The objective of present study was to formulate and evaluate bilayer tablet of Almotriptan malate (AM) and Diclofenac potassium (DP) for the effective treatment of migraine.The combination of almotriptan malate and diclofenac potassium is used as almotriptan malate establishes the immediate release layer (initialdose) and diclofenac potassium as the sustained release layer (maintenance dose) respectively.The bilayer tablets of AM and DP was particularly designed to minimize the risk of rebound migraine and improve the therapeutic efficacy and to prolong the release of drug and patient compliance.Formulation variables for immediate release layer include sodium starch glycolate and crospovidone as super disintegrants and micro crystalline cellulose as filer.HPMC K100, HPMC K15, was used as sustained release polymers.The result of in-vitro release data showed that HPMC K15 and HPMC K100 combination can sustain the drug release up to 12hrs.From these studies HPMC K15 and HPMCK100 combination has been selected for further studies of bilayer tablet.Almotriptan malate and diclofenac potassium bilayer tablet were prepared by direct compression method.The hardness of the bilayer tablets was 6.30±0.17kg/cm 2 .The thickness of the bilayer tablets was 5.19±0.10mm.The drug content of Almotriptan malate and Diclofenac potassium was 98.10±0.90(SR) and 98.84±0.09(IR).The in-vitro drug release of bilayer tablets have Almotriptan malate immediate release was within 45minutes and Diclofenac release from the tablets was found sustained over 12 hours with Zero order equation to analyze the release pattern of the drug from the polymeric system.The value of "n" were in the range of 8.0454, indicating the drug release followed Super case-II transport diffusion, possibly owing to chain distanglement and swelling of hydrophilic polymer.The Fourier transform infrared spectroscopy (FT-IR) analyses indicated that there was absence of any chemical interaction between the drugs and excipients.

Background of the Topic: The major purpose of this study was to produce a bilayer pill that contained Granisetron HCl (GSH) and ibuprofen (IBF) in distinct layers to minimize the possibility of adverse drug interactions and maximize the efficacy of both medications when they were combined to treat the symptoms of migraines. In contrast to the IBF layer, the GSH layer was intended to have a more gradual release of its contents. Methods: Microcrystalline cellulose, sodium starch glycolate, and croscarmellose sodium were the chemicals used to create the rapid-release layer. Isopropyl alcohol, magnesium stearate, and HPMC K 4M were among the polymers and gums that were used in the process of producing the continuous release layer. First, the fine-tuning process was performed on the tablet's two layers. After that, the layers necessary for quick as well as extended-release were put together. There were no adverse reactions caused by the active components interacting with the excipients. The rate at which a medicine is absorbed into the body may be sped up by using Croscarmellose sodium in a formulation. Results: A combination is given a delayed release influence by the addition of HPMC K 4M. The bilayer tablet forms from the improved (IR-4) batch were found to have strong linearity as shown by the regression coefficient of 0.9773, which is a first-order equation. According to the results, a bilayer pill that has both an increased IR-4 GSH immediate release layer and an SR-5 IBF sustained release layer would be an effective way to treat migraines. Conclusion: Bilayer tablets with releasing qualities provide a wide variety of benefits, some of which include the ability to localize medication administration, enhanced absorption, and improved effectiveness.

Background: Apixaban is a factor Xa inhibitor, an anticoagulant; that exhibits low oral bioavailability (around 50%) as a result of its extensive first-pass metabolism, which highlights the need for improved delivery methods. Aim: This research is carried out to formulate and evaluate a bilayered buccal tablet formulation of Apixaban that adheres to mucosal surfaces. Materials and Methods: Apixaban was obtained from (NATCO Pharma Limited-Chemical Division, Hyderabad); The specified qualities were achieved in formulations (F1 to F9) by varying the amounts of polymers such as sodium alginate, hydroxypropyl methylcellulose (HPMC K4M), and Carbopol (934p). To make mucoadhesive bilayered buccal tablets, the direct compression method was employed. Tablets were evaluated for physicochemical properties (thickness, weight, hardness, drug content), mucoadhesive strength, in vitro drug release, and stability. Fourier-Transform Infrared (FTIR) spectroscopy assessed drug-excipient compatibility. Results: The optimized formulation (F7), with its 20 mg of Carbopol, was emerged from a series of testing. Excellent drug uniformity (approximately 99%), and strong adhesive properties. Drug release testing showed nearly 88% release within 180 minutes, following the first-order and Higuchi diffusion model (R² = 0.9904). FTIR confirmed no drug-excipient interactions, and stability studies at 40 °C / 75 % RH demonstrated physical and chemical integrity over three months. Conclusion: The formulated buccal mucoadhesive bilayer tablets provide a potentially effective, non-invasive route for apixaban administration that circumvents hepatic metabolism and enhance bioavailability. Keywords: Apixaban, Bilayered Buccal Tablet, Mucoadhesion, Direct compression method, Carbopol.

The present study is an attempt to develop bilayer matrix tablets of Nebivolol Hydrochloride and Valsartan with immediate release for Nebivolol Hydrochloride and sustained release for Valsartan. Superdisintegrants such as sodium starch glycolate and Crosscarmellose sodium were evaluated for immediate release of Nebivolol Hydrochloride and polymers HPMC K100M and K4M for sustained release of Valsartan. Preformulation studies were performed prior to compression. The compressed bilayer tablets were evaluated for weight variation, thickness, hardness, friability, drug content and in vitro drug release using USP dissolution apparatus type 2 in 0.01N HCl and phosphate buffer pH 6.8. All the pre and post compression parameters were found to be within the acceptable limits. The results of dissolution show that the formulations B3 was the best of all immediate and sustained release layer batches. The release kinetics of Valsartan was subject to curve fitting analysis in order to identify the best fit kinetic model. The regression analysis proves that the best formulations follow zero order release and drug release by diffusion process based on Fick’s law of diffusion. The data for stability studies infer no considerable change in drug content and dissolution rates as per ICH guidelines. The best formulation B3 was subjected to in vivo pharmacokinetic studies in rabbit model. In vitro, In vivo correlation (IVIVC) showed considerable linearity. Hence a novel bilayer tablet formulation of Nebivolol Hydrochloride and Valsartan was successfully developed by combining both immediate (IR) and sustained (SR) release layers.&#x0D; Keywords: Bilayer tablets, fixed unit dosage form, Nebivolol hydrochloride, Valsartan, LC-MS analysis.

The goal of the work described in the passage was to develop bi-layer tablets of Aceclofenac, a strong non-steroidal anti-inflammatory medication, with both immediate and sustained release characteristics.The ultimate aim was to achieve quick drug release in the stomach for immediate symptom relief and a steady release in the intestine to maintain the intended therapeutic effect.Dry granulation method is used for first layer for formulations F1 -F4 contains cross carmellose sodium and F5 -F8 contains sodium starch glycolate for immediate release.Second layer was made by wet granulation method for formulations F1 -F4 with ethyl cellulose & for formulations F5 -F8 with HPMCK100M.Various formulations are prepared to obtain desired release profile to show first layer Aceclofenac release in stomach and second layer 98% for 10 h sustained release layer.Pre-compression tests are done to all the formulation and all are passed.Formulations (F1-F8) are tested for hardness, thickness, friability, weight variation and drug content.Goal of this is to optimise the formulation that bi-layer tablet to be released immediately in the stomach and second layer to be released for 10 h in the intestine.Optimized formulation F4 contains cross carmellose sodium as super disintegrants in the first layer and ethyl cellulose in the second layer.

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.

Dissolution kinetics of a bilayer direct compress tablet was evaluated by using degassing cyclic flow UV-visible (Vis) spectroscopy with chemometrics. The model bilayer nicotinamide (NA)-pyridoxine hydrochloride (PH) 100.0 mg tablets were prepared via the dual compress method. The fast diffusion layer of the bilayer tablet contained nicotinamide, microcrystal cellulose, beta-lactose, magnesium stearate, and croscarmellose sodium. The slow release layer contained pyridoxine hydrochloride and carnauba wax. The monolayer direct compress tablets were prepared as dual ingredient (API)s formulation tablets. The degassing cyclic flow UV-Vis spectroscopy dissolution test was carried out using the prepared tablets. The dissolution test conditions were as follows: time, 60 min; temperature, 37°C; paddle method, 50 rpm, and UV-Vis spectra measurement 1 time/min. The UV-Vis spectra of the flow solution were measured in the range of 240-380 nm. API concentration was predicted by partial least squares (PLS) regression models based on UV-Vis spectra. The dissolution kinetics of the bilayer and monolayer tablets were evaluated based on the UV-Vis spectra with the predicted API concentration profile. The degassing flow system could prevent air bubbles in the flow cell at 1800 min. Therefore, simultaneous determination of NA and PH concentration based on the PLS regression was suggested to have high accuracy. PLS regression has advantages over the conventional λmax absorbance method of simultaneous determination. We found that the kinetics of the separated bilayer tablet can be evaluated by the same kinetic analysis method used for the single layer model tablet.

Multilayer and Bilayer tablets are winning popularity over single-layer tablets because of their controlled release advantages. Since each layer of API must be compatible with the others and with excipients to extend the effects of the medication or drugs and improve patient compliance, technology for creating multilayers and bilayers is less widespread than that for single-layer tablets. Hydrophilic polymers are more frequently employed in the formulation of biliary and multilayer tablets as both medication carriers and release barriers. But the ratio of using polymer is different from each other in the drug barrier layer and carrier layer that can make alteration by a researcher to develop a difference in the release rate of different APIs in a single unit of the tablet. With a larger surface area and a faster rate of drug release over time, multilayer and biliary tablets can help mitigate the non-linearity and drug interactions that arise with diffusion-controlled matrix devices. This review article covers the different techniques used to create biliary and multilayered tablets as well as the challenges associated with their formulation. Keywords: Multi-layer tablets, Bi-layer tablets, Drug release, Tablet manufacturing

Bilayer tablets of aceclofenac sodium were developed using carboxymethylated white yam (Dioscorea rotundata) starch (CWY) for a fast release layer (2.5, 5.0, and 7.5% w/w), and acid-hydrolyzed bitter yam (Dioscorea dumetorum) starch (ABY) for a sustaining layer (27% w/w). Sodium starch glycolate (SSG) and hydroxypropyl methyl cellulose (HPMC) were used as standards. The starches were characterized using Fourier Transform Infrared spectroscopy (FT-IR), particle size, swelling power, densities and flow analyses. Mechanical properties of the tablets were evaluated using crushing strength and friability while release properties were evaluated using disintegration and dissolution times. Distinctive fingerprint differences between the native and modified starches were revealed by FT-IR. Carboxymethylation produced starches of significantly (p < 0.05) higher swelling and flow properties while acid-modification produced starches of higher compressibility. Bilayer tablets containing ABY had significantly higher crushing strength and lower friability values (p < 0.05) than those containing HPMC. Crushing strength increased while friability values decreased with increase in CWY. Generally tablets containing the modified Dioscorea starches gave faster (p < 0.05) disintegration times and produced an initial burst release to provide the loading dose of the drug from the immediate-release layer followed by sustained release (300 ± 7.56–450 ± 11.55 min). The correlation coefficient (R2) and chi-square (χ2) test were employed as error analysis methods to determine the best-fitting drug release kinetic equations. In vitro dissolution kinetics generally followed the Higuchi and Hixson-Crowell models via a non-Fickian diffusion-controlled release. Carboxymethylated white yam starch and acid-modified bitter yam starch could serve as cheaper alternative excipients in bilayer tablet formulations for immediate and sustained release of drugs respectively, particularly where high mechanical strength is required.

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

The aim of the present investigation was to develop bioadhesive bilayered buccal tablets of furosemide. The tablets were directly compressed using various biooadhesive polymers like chitosan, hydroxypropyl methylcellulose (HPMC), carbopol-934 and sodium carboxy methylcellulose (sodium CMC) in different ratios and also in combination of two polymers. Ethyl cellulose (EC) was used as impermeable backing layer. Buccal tablets were evaluated for several parameters such as thickness, hardness, weight uniformity, drug content uniformity, surface pH, swelling index, in vitro drug release, ex vivo permeation studies and stability studies were conducted in human saliva. Drug-polymer compatibility studies were conducted by FTIR (Fourier Transform Infrared Spectroscopy). The optimised formulation F9 (chitosan and sodium CMC at the ratio of 40:40) showed good swelling and almost neutral pH. The optimized formulation F9 has good bioadhesive strength and ability to sustain the release of drug in 8 hours (99.84±1.47 %) and it was found to be non-Fickian. FTIR study revealed there was no interaction between drug and polymer. Stability studies of optimised formulation indicate the drug was stable in human saliva for 8 hours. Hence, the formulation of bioadhesive bilayered buccal tablets using bioadhesive polymers can able sustained the release of furosemide for buccal delivery.

The main objective of sustained release drug delivery system is to provide a steady state blood plasma level concentration which is non-toxic and therapeutically active for a longer period of time. Owing its increased patient compliance and prolonged release of action in delivering drugs several benefits can be contemplated in delivering of sustained release dosage form[1]. Among various route of drug delivery Sustained release drug delivery is most widely preferred as it’s less frequency of dosing and controls the release of drugs. Natural polymers are biodegradable and nontoxic in nature with reduced side effects. It is also eco-friendly and safe to be administered as compared to synthetic polymers. The current work was based on preparation of sustained release tablets of Propranolol Hydrochloride using natural polymers like Gum Acacia, Hibiscus Rosasinesis and Microcrystalline cellulose. Presently much attention is being paid for formulation of sustained release tablets that contains matrix system. Direct compression method was used for formulation of sustained release tablets of Propranolol Hydrochloride. The prepared tablets were evaluated for different pre-formulation studies and in vitro dissolution studies were performed using USP-III dissolution apparatus. Dissolution studies of different formulations were evaluated for 24 hours at 370C.