Formulation Of Bilayer Tablets Research Articles

Formulation Development of Metformin HCl and Repaglinide Bilayer Tablets: A Novel approach to improve Therapeutic Efficacy

Many antidiabetic drugs including sulfonyl ureas, Rosiglitazone and even Insulin have been suspected to have adverse cardiovascular effects. Lactic acidosis is the feared adverse effect of the biguanide drugs with high doses. We suggest that the mean plasma concentrations of Metformin over a dosage interval be maintained below 2.5 mg/L in order to minimize the development of this adverse effect. The present research work was an attempt to design a novel formulation to improve the oral therapeutic efficacy with optimal control of plasma drug level which contains two antidiabetic drugs Metformin HCl and Repaglinide. Bilayer tablet formulation has been developed consisting of two drug containing layers which comprises Metformin sustained mucoadhesive release layer and an immediate release layer of Repaglinide was optimised separately and constituted in bilayer tablet, a common analytical method for quantitative combined drug estimation was employed and evaluated by HPLC.

Formulation and Evaluation of Bilayer Tablets of Sustained Release Microspheres of Anti Diabetic Drugs

Formulation and Evaluation of Bilayer Tablets of Sustained Release Microspheres of Anti Diabetic Drugs

FORMULATION AND EVALUATION OF BILAYER TABLET OF METRONIDAZOLE AND DICYCLOMINE HYDROCHLORIDE FOR TREATMENT OF IRRITABLE BOWEL DISEASE

The aim of the present study was to prepare bi-layer tablet of Metronidazole and Dicyclomine Hydrochloride for the effective treatment of Irritable Bowel Disease. Metronidazole and Dicyclomine Hydrochloride were formulated as immediate and sustained release layer respectively. The rational for formulation of bi-layer tablet of these two combinations was Metronidazole (immediate release) is strong antibiotic usually applied for antidiarrheal to treat inflammation of the large intestine and Dicyclomine Hydrochloride (Sustained release) is anticholinergic drug primarily used for irritable bowel disease. Bilayer tablet was suitable for maximizing the efficacy of drugs in irritable bowel disease.

Formulation and evaluation of a bilayer tablet comprising of diclofenac potassium as orodispersible layer and diclofenac sodium as sustained release core

Diklofenak, bir fenilasetik asit turevi olup uzun yillardan beri antienfamatuvar ve analjezik bir ilac olarak kullanilmaktadir ancak bu etken maddeden hareketle hemen salim icin yukleme dozu iceren geciktirilmis salim formulasyonunun hazirlanmasi istenmektedir. Bu calismanin amaci, agizda dagilan tabaka olarak diklofenak potasyum, geciktirilmis salim cekirdegi olarak diklofenak sodyum iceren iki tabakali tabletlerin formulasyonu ve degerlendirilmesidir. Diklofenak sodyum iceren cekirdek yas granulasyon yontemi ile hazirlanirken agizda dagilan dis tabaka direct basim yontemiyle ve super dagitici olarak sodyum nisasta glikolat varliginda hazirlandi. Toz karisimi hem basim oncesi hem de basim sonrasi ozellikleri acisindan degerlendirildi. Toz karisiminin ve tabletlerin fiziksel ozelliklerinin zorunlu standartlarla uyumlu oldugu goruldu. Agizda dagilan kismin 30 saniyeden kisa bir surede dagilarak yukleme dozu olan diklofenak potasyumu saldigi, cekirdek kisminin ise simule bagirsak sivisinda (pH 6.8), 10 saate kadar diklofenak sodyum salinimi sagladigi tespit edildi. Kinetik ile ilgili veriler incelendiginde, tabletin non-fickian salim gosterdigi ve Korsmeyer-Peppas modeline uygun oldugu tespit edildi. Tek bir tablet iceriginde, agizda dagilan tabaka olarak diklofenak potasyum, geciktirilmis salim cekirdegi olarak diklofenak sodyum iceren ve super dagitici olarak sodyum nisasta glikolat iceren tabletlerin formulasyonu basariyla yapildi.

Formulation and Evaluation of Bilayer Tablets Containing Immediate Release Aspirin Layer and Floating Clopidogrel Layer

Aspirin and clopidogrel are considered the most important oral platelets aggregation inhibitors. So it is widely used for treatment and prophylaxis of cardiovascular and peripheral vascular diseases related to platelets aggregation .In this study aspirin and clopidogrel were formulated together as floating bilayer tablet system. Three different formulas of 75 mg aspirin were prepared by wet granulation method as immediate release layer; different disintegrants used to achieve rapid disintegration. Formula with crosscarmellose as disintegrant achieve rapid disintegration was selected for preparation of bilayer tablet.
 Different formulas of 75 mg clopidogrel were prepared as sustained release floating layer by wet granulation (effervescent ) method ;the physical and floating properties for compressed clopidogrel matrix were studied in addition to study the effect of polymer concentration(HPMC) ,and its combination with ethyl cellulose and carbapol ,effect of different diluents and effect of increasing sodium bicarbonate amount on the release from compressed matrix .
 Formula prepared with HPMC and EC in a ratio of 1:1 was capable to retard the release of clopidogrel for 6 hours in addition to its good floating behavior and therefore selected to prepare bilayer tablets in combination with selected aspirin layer.
 The prepared bilayer tablets were further subjected to evaluation of their physical, floating properties and release behavior. Finally the kinetic study reflects acceptable shelf life for aspirin and clopidogrel.
 Key words: Aspirin, Clopidogrel, Bilayer tablet, Floating tablet.

Systematic development of a gastroretentive fixed dose combination of lamivudine and zidovudine for increased patient compliance

The present study describes systematic development of a gastroretentive bilayer tablet formulation containing fixed dose combination of lamivudine and zidovudine exhibiting controlled drug release and floating-bioadhesive characteristics. Effervescent floating-bioadhesive bilayer tablets containing rational blend of polymers were formulated by non-aqueous granulation employing isopropyl alcohol. A face centred cubic design was employed for optimizing various critical material attributes of the bilayer tablets, which were evaluated for bioadhesive strength (BS), buoyancy time (Tb) and drug release characteristics as the critical quality attributes for each layer. The optimum composition for each layer was selected by “trading off” the magnitude of various quality attributes by maximization of BS, Tb and drug release characteristics, and demarcated in the design space. Gamma scintigraphic studies in healthy volunteers indicated gastroretentive behaviour of the optimized formulation upto 6 h, while the marketed immediate release formulation taken as control showed maximum gastroretentivity only upto 1 h. In a nutshell, these studies corroborated development of an optimal and stable once-a-day controlled release gastroretentive system of lamivudine and zidovudine.

Biointerfacial phenomena of amlodipine buccomucosal tablets of HPMC matrix system containing polyacrylate polymer/β-cyclodextrin: Correlation of swelling and drug delivery performance

ABSTRACTObjectives: This study focuses on the development of amlodipine bilayer buccal tablets of hydroxypropyl methylcellulose (HPMC) matrix system containing polyacrylate polymer (Carbopol®)/β-cyclodextrin as the drug layer and ethylcellulose as the non-swellable backing layer, and their biointerfacial phenomena.Methods: Tablets were evaluated for swelling, erosion and mucoadhesion using buccal mucosal tissue ex vivo. In vitro drug release and ex vivo drug transport across mucosal tissue were also performed in phosphate buffer (pH 6.8). The relationship of swelling with buccoadhesion and buccal permeation of various bilayer tablet formulations containing HPMC alone and in combination with Carbopol or drug-β-cyclodextrin complex has been prepared.Results: Overall buccoadhesion of the tablet with combination of HPMC and Carbopol was increased significantly compared with that of HPMC alone. Presence of cyclodextrin did not change bioadhesion force and swelling behavior significantly. Ex vivo permeation was increased with the increase of HPMC proportion in other formulations as observed in in vitro dissolution.Conclusion: Drug–cyclodextrin complexes in the tablet improved permeation due to its improved dissolution at the site of biointerface of tablet and buccomucosa. Correlations of ex vivo and in vitro data have been established to predict the buccomucosal permeation from the swelling index or drug release alone.

Formulation and Evaluation of Gastro-bilayer Floating Tablets of Simvastatin as Immediate Release Layer and Atenolol as Sustained Release Layer

Combination therapy is highly desired to deliver atenolol and simvastatin for dyslipidemia and hypertension for concomitant drug treatment. On other hand, atenolol has poor absorption in lower gastrointestinal tract, short half-life and simvastatin has poor solubility. Therefore, the present study was to develop gastro-bilayer floating matrix tablet in which simvastatin was incorporated as immediate layer and atenolol as sustained release layer. Gastro-bilayer floating tablets were prepared by direct compression method and optimized using hydroxypropyl methylcellulose K100 (37.5%) as release retardant and sodium bicarbonate as a gasforming agent. The immediate release layer comprised sodium starch glycolate as superdisintegrant. The tablets of optimized formulations floated on the test medium for more than 12 h with 9 min of floating lag time. Atenolol release was sustained for 12 h via diffusion mechanism and more than 96% release of simvastatin within 15 min was achieved. It can be concluded that, the biphasic drug release pattern was successfully achieved through the formulation of gastro-floating bilayer tablets in this study, allowing strengthened combination therapy for hypertension and dyslipidemia.

Spectroscopic Investigations for Photo Stability of Diclofenac Sodium Complexed with Hydroxypropyl-beta-Cyclodextrin

Formulation and Evaluation of Bilayer Tablets of Diclofrenac Sodium with Ranitidine HCL for Sustained and Immediate ReleasePrabhakar Shirse

Formulation and evaluation of bilayer tablet for bimodal release of venlafaxine hydrochloride.

The aim of the present research was to develop a bilayer tablet of venlafaxine hydrochloride for bimodal drug release. In the present investigation authors have tried to explore fenugreek mucilage (FNM) for bioadhesive sustained release layer. The attempt has been made to combine FNM with well studied bioadhesive polymers like hydroxy propyl methyl cellulose (HPMC), Carbopol, and Xanthan Gum. The formulations were evaluated for swelling Index, ex vivo bioadhesion, water uptake studies, in vitro drug release and dissolution kinetics was studied. Substantial bioadhesion force (2.4 ± 0.023 g) and tablet adhesion retention time (24 ± 2 h) was observed with FNM and HPMC combination at 80:20 ratio. The dissolution kinetics followed the Higuchi model (R2 = 0.9913) via a non-Fickian diffusion controlled release mechanism after the initial burst. The 32 full factorial design was employed in the present study. The type of polymers used in combination with FNM (X1) and percent polymer replaced with FNM (X2) were taken as independent formulations variables. The selected responses, bioadhesion force (0.11–0.25 ± 0.023 g), amount of drug released in 10 h, Y10 (78.20–95.78 ± 1.24%) and bioadhesive strength, (19–24 ± 2 h) presented good correlation with the selected independent variables. Statistical analysis (ANOVA) of the optimized bilayer formulations showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p < 0.05) in the amount of drug released after 1 hr till 12 h from optimized formulations was observed. The natural mucilage like FNM could be successfully incorporated into tablet with only 20% replacement with HPMC and it showed good bioadhesiveness and sustained drug release.

Design of bilayer tablets using modified Dioscorea starches as novel excipients for immediate and sustained release of aceclofenac sodium.

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.

Design of Gastroretentive Floating Bilayer Tablets of Metformin and Glimepiride

The present study involves designing and development of a bilayer tablet of Metformin HCl (MET) and Glimepiride (GLP) to offer immediate release of GLP and gastroretentive layer of MET. Bilayer tablets containing two layers i.e. immediate release layer formulated using super disintegrant Sodium starch glycolate and gastroretentive layer formulated with polymers like HPMC K4M and HPMC K100M to modulate the biphasic drug release. Wet granulation method was employed to formulate bilayer tablets. Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM) were used for physicochemical compatibility and stability studies of the tablets. Accelerated stability studies were followed in compliance with ICH guidelines. The in vitro release profile shows desired biphasic release behavior after storage at accelerated condition (40°C± 2°C and 75%RH ± 5% RH) for 6 months. Biphasic drug release pattern was successfully achieved through the formulation of bilayer tablets that are stable and capable of releasing the drug over 12 hrs.

Formulation and Evaluation of Bilayer tablets of Metoprolol Succinate

Metoprolol is β-1 blocker drug and used in treatment of angina pectoris and hypertension. Metoprolol 100mg tablets were formulated as a modified release oral system by utilizing the concept of bilayer tablets in which 30mg drug was added as immediate release (IR) and 70 mg as extended Release (ER). The IR layer consists of lactose or microcrystalline cellulose which acts as diluents with sodium starch glycolate or crosscarmellose as superdisintegrant. The blend was evaluated for angle of repose, bulk and tapped density, Hausner's ratio, Carr's index. The bilayer tablets were prepared manually using 9 station tablet punching machine. The prepared bilayer tablets were evaluated for hardness, thickness, friability, uniformity of weight and in vitro dissolution study. The bilayer tablets were also examined for drug content, kinetic of drug release and stability study. The results showed that the immediate release layer comprising MCC and 2% SSG released 95% drug in 60mins. The sustained release layer was prepared by three polymers i.e. HPMC K 100, HPMC K 15M and HPMC K 4M. It was found that HPMC K 4M in 20% concentration sustained the release of metoprolol succinate to 12hrs. It was concluded that batch BL-3 exhibited desirable properties and optimized drug release. The in vitrodrug release of batch BL-3 was satisfactory. Hence batch BL-3 was considered as optimized batch.

Bilayer Tablet Formulation of Metformin HCl and Acarbose: A Novel Approach To Control Diabetes

The present investigation studied a novel bilayer tablet having an extended release system of metformin HCl with Eudragit RS 100 and RL 100 and an immediate release system of acarbose with polyvinylpyrrolidone K30 (PVP K30) and polyethylene glycol 6000 (PEG 6000) in different ratios using solvent evaporation and cogrinding techniques. Solid dispersions (SDs) were characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), powder x-ray diffractometry (XRD), scanning electron microscopy (SEM), as well as by content uniformity, in vitro dissolution studies, and release kinetics. The selected SD system was subjected to bilayer tablet preparation by direct compression. Compressed tablets were evaluated for drug content, weight variation, friability, hardness, and thickness, and they underwent in vitro dissolution studies. The progressive disappearance of IR, x-ray, and thermotropic drug signals in SDs and physical mixtures were related to increasing amount of polymer. SEM studies suggested the homogenous dispersion of drug in polymers. FT-IR studies confirmed the formation of hydrogen bonding between drug and polymer. All tablet formulations showed compliance with pharmacopoeial standards. The formulations gave an initial burst effect to provide the loading dose of the drug followed by extended release for 12 h (Higuchi model via a non-Fickian diffusion controlled release mechanism). Stability studies conducted for the optimized formulation did not show any change in physical properties, drug content, or in vitro drug release. The goal of diabetes therapy today is to achieve and maintain as near normal glycemia as possible to prevent the long-term microvascular and macrovascular complications of elevated blood glucose levels. Oral therapeutic options for the treatment of type 2 diabetes mellitus, until recently, have been severely limited. Metformin, a biguanide, targets additional mechanisms of hyperglycemia by inhibiting hepatic glucose production and enhancing peripheral glucose uptake and thereby reducing insulin resistance; acarbose reversibly bind to pancreatic alpha-amylase and membrane-bound intestinal alpha-glucoside hydrolases. These enzymes inhibit hydrolysis of complex starches to oligosaccharides in the lumen of the small intestine and hydrolysis of oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the brush border of the small intestine. The two agents were found to have a remarkable effect on glycemic control. In the present investigation a bilayer tablet was prepared in which one layer gives instant action against diabetes and another layer maintain concentration of drug in plasma for longer periods.

Formulation and Evaluation of Bilayer Tablets of Glimepiride and Metformin HCL

The objective of the present investigation was to prepare bilayer tablets of Glimepride and Metformin HCL in combination. Metformin hydrochloride and Glimepiride are oral hypoglycemic drug and effectively used in treatment of diabetes mellitus (type-2 diabetes). The main aim of the present study was to formulate Metformin hydrochloride sustained release and Glimepride immediate release matrix tablets as a dosage form by different polymers such as HPMC, Povidone, Lactose Monohydrate, Ethylcellulose, Microcrystalline Cellulose and study the invitro release patterns of the drug. In the present study bilayer tablets Glimepride prepared by direct compression method and Metformin prepared by wet granulation technology. The prepared tablets were evaluated for various physicochemical parameters such as drug-excipient interaction by FTIR,flow properties, hardness, weight variation, friability, and in vitro dissolution studies optimised based on desired sustained release time (16hrs) and acceptable floating properties The FTIR study revealed that there is no drug-excipient interaction. During preformulation it has been observed that there is no drug- drug and drug excipient interaction, so the excipients which have been selected for the formulation are compatible with the drugs. This system provides zero order or near zero order release for IR layer and SR layer provides Higuchi model.

Validated reverse phase-high performance liquid chromatography method of amoxicillin trihydrate for assay and dissolution studies in time-dependent release bilayer tablet formulations

Background: Amoxicillin trihydrate is used a broad spectrum antibiotic for the treatment of diverse variety of bacterial infections. Aim: The objectives of the present study was an assessment of in vitro drug release profile and estimation of the drug content of the prepared in-house time-dependent release bilayer tablet formulations of amoxicillin trihydrate (AMT) employing a simple, rapid, sensitive and a cost effective reverse phase liquid chromatography method. Materials and Methods: The chromatographic separation was achieved using methanol and phosphate buffer (pH 3.5) at 50:50% v/v as mobile phase at a flow rate of 1 mL/min. Results: The method was validated for linearity, accuracy, precision, limit of detection, limit of quantitation and system suitability. The linearity was determined by residual analysis indicated good regression coefficient ( r 2 ) of 0.999 at a concentration ranging between 2 and 16 μg/mL. The assay of both in-house formulation and marketed preparation indicated good recovery of 99.95% and 99.60%, respectively. In vitro dissolution studies revealed that the prepared in-house tablet formulation showed time-dependent biphasic profile of drug release, whereas marketed preparation showed immediate release effect. Conclusions: The developed method, therefore, can be used for routine estimation of AMT in bulk and pharmaceutical dosage forms.

Design, Development and Evaluation of Chronomodulated Drug Delivery Systems of Amoxicillin Trihydrate with Enhanced Antimicrobial Activity

The present studies entail the formulation development and evaluation of chronomodulated drug delivery system of amoxicillin trihydrate (AMT), which comprises of a bilayer tablet containing a delayed release and a sustained release layer. Direct compression method was employed for the preparation of bilayer matrix tablets containing rational blend of polymers, such as Eudragit-L100 D55 as delayed release polymer and HPMCK4M, HPMCK15 and HPMCK100 are sustained release polymers. In- vitro drug release studies of bilayer tablets observed a good sustained release action with time-dependent burst release after a lag-time of 3 hrs. Evaluation of drug release kinetics from sustained release layer of bilayer tablets followed Higuchi model via quasi-Fickian diffusion mechanism. SEM studies revealed formation of pores on sustained release layer, which confirmed the drug release through diffusion and predominantly by surface erosion mechanism. Evaluation of antimicrobial activity showed a decrease in minimum inhibitory concentration of optimized bilayer tablets vis-à-vis conventional marketed formulation. Accelerated stability studies revealed that the optimized bilayer tablet formulation was found to be stable upto the period of 6 months. Solid state characterization employing FT-IR and DSC studies indicated lack of significant interaction of drug with formulation excipients. Thus, the present studies ratify the suitability of chronomodulated bilayer tablets of AMT for effective management of bacterial infections owing to specific time-dependent drug release, higher gastric protection and enhanced antimicrobial activity.

Pharmacokinetic Studies in Healthy Subjects for the Development of an Extended-Release Tablet Formulation of Guaifenesin: A 505(b)(2) New Drug Application Approval.

Guaifenesin is an expectorant used to improve mucociliary clearance (MCC) and relieve chest congestion from upper respiratory tract infections. Immediate-release (IR) guaifenesin requires dosing every 4 hours to maintain efficacy because of the drug's short half-life. Extended-release (ER) guaifenesin has been developed to prolong efficacy and reduce dosing frequency. As part of the 505(b)(2) new drug application (NDA), the pharmacokinetics (PK) of an ER bi-layer tablet formulation of guaifenesin (Mucinex®) and bioequivalence to an over-the-counter (OTC) monograph IR formulation were evaluated in healthy subjects. In one study, subjects received 1,200 mg ER guaifenesin every 12 hours or 400 mg IR guaifenesin every 4 hours for 6 days. Steady-state exposures were equivalent between the two products, as demonstrated by AUC and Cmax . In another study, subjects received a single dose of 600 mg (fasted) or 1,200 mg (fasted or fed) ER bi-layer tablet formulations. AUC and Cmax were equivalent between both states for the 1,200 mg ER dose. However, Tmax of 1,200 mg ER guaifenesin was later in the fed than the fasted state. ER guaifenesin is bioequivalent to corresponding OTC monograph doses of IR guaifenesin. ER guaifenesin offers a convenient 12-hour dosing alternative to 4-hour dosing of IR guaifenesin.

Mechanistic characterization of bilayer tablet formulations

The interest in bilayer tablet as an oral immediate-release/controlled-release system has substantially increased in the past decade. However, during the production of such tablets, lack of sufficient bonding and adhesion at interfaces between adjacent layers is compromising the mechanical integrity and performance of the final solid dosage form. In this study, bilayer tablets of the widely used excipient microcrystalline cellulose in the form of Avicel 102 and pregelatinized starch were formed with different pre-compression (2 kN, 4 kN, 6 kN, 8 kN) and final compression (6 kN, 10 kN, 14 kN, 18 kN) forces to quantitatively characterize the strength (σ) of the interface and the compacted adjacent layers. Bilayer tablets were axially debonded (i.e., separation of adjacent layers that are subjected to axial loading) until fracture and axial tensile strength values were determined. It was observed that when the first layer was compressed to a low porosity, the bonding with the second layer became difficult and it was not possible to produce intact bilayer tablets (σlayer > σinterface). It has been demonstrated that the material response of the constrained MCC particles to an applied initial compression force within the initial compacted layer have a detrimental effect on the resistance to fracture of a bilayer tablet. The mechanism of failure at the interface or at the individual layers was also studied. Different fracture patterns, namely, clear layer break, half–half break, cap-shape break, and clear interface break were observed as a function of various initial and final compression forces. X-ray micro-computed tomography (μCT) was utilized to examine the influence of localized density distribution on the delamination (layer separation) phenomena of bilayer tablets. It has been shown that once the magnitude of the applied final layer compaction stress greatly exceeds the initial layer compaction stress, the tablet catastrophically fails at the initial layer not at the interface (σlayer < σinterface). The results of this study point out that the measurement of the interfacial strength provides insight into some of the major complications of bilayer tablets.

Formulation and Evaluation of Bilayer Tablets of Diclofrenac Sodium with Ranitidine HCL for Sustained and Immediate Release

The aim of present study is to formulate and evaluate the bilayered tablets containing Diclofenac Sodium in the sustained release (SR) portion and Ranitidine HCl in the immediate release (IR) portion in order to produce a single tablet containing two different classes of drugs as widely prescribed by doctors and to have better patient compliance.The sustained release layer of Diclofenac Sodium was prepared by using different grades of HPMC like, HPMC E15, HPMC K4M, K100M, and Ethyl Cellulose with cross carmellose along with other excipients like Magnesium stearate, Microcrystalline cellulose & PVP by wet granulation technique. The Immediate release layer of Ranitidine Hcl was prepared by direct compression Method. The powders were evaluated for their flow properties and the finished tablets were evaluated for their physical parameters. The drug release study of Ranitidine HCl and Diclofenac Sodium were evaluated using USP-XXII paddle type dissolution apparatus. The release rate of Ranitidine HCl was studied for 45 min using water as media and that of Diclofenac Sodium was studied for 2 h in 1.2pH buffer followed by 6 h in pH 6.8 phosphate buffer media using a developed HPLC method. The release rate of ranitidine HCl from all the formulations was more than 80% at 45 min. In case of HPMC E15, HPMC K4M, K100M based tablets with the increasing of polymer content the release mechanism moved to super case. Total four trial batches of each drug have been manufactured to optimize and develop a robust and stable formulation, the stability studies of the products also comply with ICH guidelines.