Melt Granulation Technique Research Articles

Formulation Development and Evaluation of Sustained Release Matrix Tablets of Guaiphenesin

In this study we sought to formulate and evaluate sustained release matrix tablet of guaiphenesin by melt granulation technology. The sustained release tablets were prepared by melt granulation technique using rice bran wax as a drug retardant and dibasic calcium phosphate (DCP) as a channelling agent. Guaiphenesin is an expectorant and has a short plasma half-life of one hour. Because of high frequency of administration and short biological half-life, guaiphenesin was considered as model drug. Sustained release formulation that would maintain plasma levels for 12 hours is sufficient for twice daily dosing of guaiphenesin. The compatibility of drug and wax was examined by differential scanning calorimetry (DSC). The effect of waxes at different (drug: wax) concentrations on the release profile of drug from matrix formulation were studied. Drug release was studied at pH 1.2 for 2 hour and pH 6.8 for 10 hours. A significant retardation in the drug release was observed by increasing the wax concentration. The drug release study revealed that wax concentration of 30% to be optimum. Dissolution study showed 99% drug release within 12 hrs. Kinetic modelling of in vitro dissolution profiles revealed the drug release mechanism ranges from diffusion controlled or Fickian transport to anomalous type or non-Fickian transport. These results suggest that the rice bran wax has good release retardant property for highly water-soluble drug such as guaiphenesin.

Formulation Development and Optimization of Ibuprofen Poloxamer Melt Granules Using Hydrophilic Excipients

The focus of this research work was to develop a melt granulation technique to enhance solubility, dissolution rate and associated flowability concerns of Ibuprofen. Hydrophilic excipients like xylitol and lactose anhydrous were added to the binary mixture of conventional low melting surfactant Poloxamer 407 and Ibuprofen. Physical mixtures of Ibuprofen and Poloxamer 407 were prepared in ratios of 1:0.25, 1:0.5 and 1:0.75 using a water-jacketed high shear mixer. For each ratio of Ibuprofen and Poloxamer 407, xylitol and lactose anhydrous were added separately at two levels (75 mg and 150 mg) per unit dose containing 200 mg drug. Phase solubility studies revealed linearity in drug solubility enhancement with Poloxamer 407 concentration. In vitro dissolution studies were carried out for drug, physical mixtures (PM) and melt granules (MG) for all ratios in de-ionized water and 0.1 N HCl (pH=1.2). Solid state characterization was performed using Fourier transform infrared spectroscopy (FTIR), modulated differential scanning calorimetry (mDSC) and powder X-ray diffraction (PXRD) methodologies. Powder rheology studies were performed conventionally by measuring Carr’s index and Hausner’s ratio. Basic flowability energy values were calculated using a powder rheometer to corroborate flowability data measured by conventional methods. Particle morphological studies were done by Scanning electron microscope (SEM) and Fluid imaging technologies. In-vitro dissolution studies showed approximately 7 fold drug release in water and 19 fold drug release in acidic media for MG 1:0.75 at hydrophilic excipient level of 150 mg compared to that of neat Ibuprofen in respective dissolution media. mDSC and PXRD data confirms crystalline nature of drug in the formulations. FTIR data confirms no interactions between drug and excipients used during processing. Particle morphology analysis confirms absence of rhombic Ibuprofen crystals in formulations. Dissolution rate and solubility enhancement was seen due to synergistic effects of Poloxamer 407 and hydrophilic excipients incorporated in formulations.

Modulation of drug release mechanism by Higuchi model: Estimation of percent deviation

The objective of this study was to develop Nicorandil floating tablets by melt granulation technique using combination of almond gum as swellable plus retarding polymer and cetosteryl alcohol as waxy plus retarding polymer. The drug release mechanism is analysed by both Higuchi model and Hixson-Crowell model based on their higher square of correlation coefficient (R2). The best formulation of MCS4 is selected based on the identical drug release profile with theoretical release data calculated from Robinson Erickson equation which follows Higuchi model for drug release from tablet core. Further, the drug release of best formulation which follow Higuchi model is checked for its deviation from an ideal Higuchi release profile. The release profiles of the best formulation is greatly deviate the ideal Higuchi release profile. In order to minimise the deviation, twotiered method is used and confirm the drug release at two phases as Hixson-Crowell model for first phase and Higuchi model for second phase.

Calculation of predominant drug release mechanism using Peppas-Sahlin model, Part-I (substitution method): A linear regression approach

The objective of this study was to develop Nicorandil controlled release floating tablets using combination of hydrophilic and hydrophobic polymers by melt granulation technique. The in vitro drug release characteristics were determined using USP XXII type 2 (paddle type) apparatus, in a medium of 0.1N HCL. The dissolution profile of all the batches were extended up to 24 hrs. To study and model the drug delivery from polymeric floating tablets, the dissolution data was fitted to a pioneered method Korsmeyer-Peppas equation. The results indicate that, all the formulations followed super Case-II release mechanism, except MCS4 which followed non- Fickian or anomalous release mechanism. In order to determine the predominant mechanism (diffusion/ relaxation model), drug release data was incorporated into Peppas-Sahlin model. The results revealed that, Fickian release contribution was preponderance than corresponding Case-II relaxational contribution in all the formulations. In addition to this, the relaxational contribution was observed with negative sign in all the formulations but, only at specific time intervals. Relaxational contribution with negative values indicates the Fickian release mechanism was more pronounced than relaxation i.e. almost the relaxational mechanism was absent.

EMERGING TREND IN ADRESSING THE CHALLENGES TO ORAL NANOCURCUMIN DELIVERY TO IMPROVE QUALITY OF LIFE OF PATIENTS SUFFERING FROM CANCER

Present work was investigated for enhancement of solubility, bioavailability and anti-cancer activity of curcumin, a potent natural anticancer agent. Solid microdispersion of curcumin was prepared by melt granulation technique using Gelucire® 50/13 as a hydrophilic carrier followed by adsorbtion on Aeroperl® 300 Pharma. Compatibility among curcumin and excipients were checked using FT-IR, DSC and XRD analysis. The prepared microdispersion was characterized for percent drug content, entrapment efficiency, surface morphology, particle size, solubility, bio-availability and anticancer activity. DSC analysis study had shown complete encapsulation of raw curcumin which was further supported by XRD study showing flat peaks. A 32 full factorial response surface quadratic model demonstrated the positive effect upon change in the concentration of independent variables viz. Gelucire® 50/13 and Aeroperl® 300 Pharma on dependent variables particle size; % entrapment efficiency. TEM analysis confirmed the nano particulate dispersion upon dilution in distilled water with many fold increased in solubility. Maximum solubility was observed in acidic buffer pH 1.2. In vivo study revealed increased in bio-availability in Wistar rats as compared to raw curcumin by HPLC analysis. In MTT assay study, curcumin microdispersion has shown more prominent anti-cancer activity than raw curcumin on breast cancer cell line culture, MCF-7. From above study, it may be concluded that implementation of this innovative approach could be a better alternative for oral nanocurcumin delivery to improve the quality of life patients suffering from cancer.

Formulation and development of pH-independent/dependent sustained release matrix tablets of ondansetron HCl by a continuous twin-screw melt granulation process

The objective of the present study was to develop pH-independent/dependent sustained release (SR) tablets of ondansetron HCl dihydrate (OND), a selective 5-HT3 receptor antagonist that is used for prevention of nausea and vomiting caused by chemotherapy, radiotherapy and postoperative treatment. The challenge with the OND API is its pH-dependent solubility and relatively short elimination half-life. Therefore, investigations were made to solve these problems in the current study. Formulations were prepared using stearic acid as a binding agent via a melt granulation process in a twin-screw extruder. The micro-environmental pH of the tablet was manipulated by the addition of fumaric acid to enhance the solubility and release of OND from the tablet. The in vitro release study demonstrated sustained release for 24h with 90% of drug release in formulations using stearic acid in combination with ethyl cellulose, whereas 100% drug release in 8h for stearic acid-hydroxypropylcellulose matrices. The formulation release kinetics was correlated to the Higuchi diffusion model and a non-Fickian drug release mechanism. The results of the present study demonstrated for the first time the pH dependent release from hydrophilic-lipid matrices as well as pH independent release from hydrophobic-lipid matrices for OND SR tablets manufactured by means of a continuous melt granulation technique utilizing a twin-screw extruder.

Formulation and Evaluation of Floating Drug Delivery System Using Losartan

The present study was aimed at preparing a Floating drug delivery system for the model drug Losartan, and evaluating the various processing parameters including the buoyancy studies and in vitro drug release studies. Four formulations containing varying proportions of polymers like HPMC K4M and Ethyl cellulose and fixed amount of gas generating agent such as Sodium bi carbonate, material like bees wax were prepared. The tablets were prepared by melt granulation technique and the prepared tablets remained buoyant for more than 8hrs in the release medium. The proportions of the polymers showed significant difference in the release of the drug. All the formulations exhibited diffusion dominant drug release and were found to be stable.

Development of Hydrophobic Carriers based tablets for Sustained Release of Verapamil

Article history: Received on: 13/09/2015 Revised on: 02/10/2015 Accepted on: 26/10/2015 Available online: 27/12/2015 The main aim of the study is to formulate sustained release matrix tablets of verapamil hydrochloride using hydrophobic carriers or meltable binders like stearic acid, carnauba wax and bees wax by melt granulation technique. The influence of a hydrophilic polymer like polyethylene glycol (PEG) was studied on the waxy matrices. Two grades of PEG (4000 and 6000) were used in the preparations. The granules were prepared and compressed into tablets and they are evaluated for their physicochemical properties and in vitro dissolution studies were done. The IR spectral analysis revealed that there are no interactions between drug and the polymers and are compatible with other. The release data were subjected to various release kinetic models and also compared with those of a commercial brand. The tablets prepared fulfilled all the official requirements according to the pharmacopeia. From the dissolution studies it was observed that carnauba wax acts a good retardant (more than 16 h). Among the two grades of PEG used 4000 and 6000, PEG 6000 increases the drug release to a greater extent than PEG 4000. It was concluded that hydrophobic carriers which act as very good retardants of the drug and also PEG can be used as a channeling agent in waxy matrices to regulate the release of the drug.

Development of novel multifunction directly compressible co-processed excipient by melt granulation technique.

Introduction:The objective of the present investigation was to develop a novel multifunctional directly compressible co-processed excipient consisting of dibasic calcium phosphate anhydrous, polyethylene glycol 4000 (PEG 4000) and crospovidone using Box-Behnken design.Materials and Methods:The technique of melt granulation was adopted for the preparation of the co-processed excipient. The percentage of crospovidone (5-10% w/w), percentage of PEG 4000 (5-15% w/w) and the heating time (4-12 min) were selected as independent variables. The co-processed granules were evaluated for bulk density, tapped density, Hausner's ratio and Carr's index. Placebo tablets of co-processed granules were prepared and evaluated for hardness, friability and disintegration time. Multiple linear regression was applied to develop mathematical models for hardness, Carr' index and disintegrating time. ANOVA was applied to study the fitting and significance of the model. The optimized batches (BB) were selected for further studies. The selected batches were characterized for particle size distribution, granular friability index, moisture uptake study, differential scanning calorimetry, Fourier transform infrared spectroscopy and scanning electron microscopy. Aceclofenac was selected as model drug for the preparation of tablets.Results:Aceclofenac tablets prepared using co-processed excipients showed better hardness, disintegration time and in vitro drug release as compared to aceclofenac tablets prepared using conventional wet granulation method.Conclusion:The developed co-processed excipient can serve as a novel co-processed excipient for improvement of tableting characteristics.

Design and development of co-processed excipients for fast dissolving tablets of Irbesartan by melt agglomeration technique

The co-processing is most widely explored method for development of directly compressible excipients. The present research was focused on development of co-processed excipients for fast dissolving tablets of Irbesartan by melt agglomeration technique. From the preliminary trials Lactose monohydrate and mannitol was selected as a diluent and Poly ethylene glycol 4000 as binder. To improve functionality of co-processed excipients 8 % crospovidone was incorporated. Diluent blend ratio and concentration of binder (%) were selected as independent variables in central composite design. The agglomerates were evaluated in terms of % fines, angle of repose, Carr’s index, Hausner ratio. The tablets were manufactured on a rotary press and their friability, tensile strength and disintegration time were evaluated. This optimized batch was characterized by means of the granular friability index, Heckel analysis, Kawakita, Kuno’s analysis, lubricant sensitivity ratio and a dilution potential study. Result of dilution potential showed that up to 40 % drug can be incorporated. In addition to these, bitter taste of drug was masked by forming drug—β-cyclodextrin inclusion complex and by adding aspartame as a Sweetener. Compared to conventional tablet it showed faster dissolution. Instrumental studies like Fourier transform-infrared spectroscopy, differential scanning calorimetry, X-ray diffraction showed that the compatibility of various excipients with drug. The present study underlines the fact that melt granulation technique may be adopted for the development of directly compressible adjuvant for use in pharmaceuticals.

Formulation Development and Optimization of Floating Granules of Acyclovir by Melt Granulation Technique

The purpose of this research was to develop and optimize a sustained-release multiple unit floating system of a highly water-soluble drug, Acyclovir, using Gelucire 43/01 as lipid carrier and ethyl cellulose (EC) and methyl cellulose (MC) as release rate modifiers. Floating granules containing acyclovir were prepared by the melt granulation technique and evaluated for drug release and in vitro floating ability. A 23 full factorial design was used for optimization by considering the ratio of drug to Gelucire 43/01, EC, and MC as independent variables and the percentage drug released in 8 h (Q8) and in vitro floating ability as dependent variables. The granules were evaluated for physical characterization, percentage practical yield, scanning electron microscopy, differential scanning calorimetry, FTIR, drug content, in vitro floating ability, and in vitro drug release. The floating granules had good flow properties and irregular shape with rough surface. The optimized formulation showed good floating ability and 98% drug was released in 8 h. In conclusion, hydrophobic lipid, Gelucire 43/01, can be considered as an effective carrier for design of a multiunit floating drug delivery system of highly water-soluble drugs such as acyclovir.

Preparation of Solid Dispersion of Everolimus in Gelucire 50/13 using Melt Granulation Technique for Enhanced Drug Release

Solid dispersion (SD) system of everolimus (EVR) with Gelucire 50/13 (Stearoyl polyoxyl-32 glycerides) was prepared using melt granulation technique with the aim of improving the physicochemical properties and dissolution rate. The solid state characterization using scanning electron microscopy and X-ray powder diffraction, indicated that the drug was homogeneously distributed in the surfactant carrier in a stable amorphous form. The dissolution rate of EVR from the optimized SD composed of the drug, Gelucire 50/13 and microcrystalline cellulose in a weight ratio of 1:5:10, was markedly rapid and higher than that from the drug powder and the market product (Afinitor<TEX>$^{(R)}$</TEX>, Novartis Pharmaceuticals) in all dissolution mediums tested from pH 3.0 to pH 6.8. The results of this study suggest that formulation of SD with Gelucire 50/13 using melt granulation procedure may be a simple and promising approach for improving the dissolution rate and oral absorption of the anti-cancer agent without the need for using an organic solvent.

PREPARATION AND EVALUATION OF SUSTAINED RELEASE TABLET OF EPERISONE HYDROCHLORIDE BY COMPRITOL ATO 888 AS A MATRIX FORMING AGENT.

Objective: The objective of this work was to prepare and evaluate oral sustained release matrix tablet of highly water soluble drug and to study the effect of proportion of wax and addition of release liner on in-vitro release of drug. Method: The matrix tablets were prepared by melt granulation method using drug:wax in 1:1, 1:2 &amp; 1:3 proportions and evaluated for on in-vitro drug release. Then the proportion 1:1 was selected and wax matrix tablets were prepared by three techniques melt granulation, wet granulation and direct compression to check their in-vitro release profiles. Results: The study revealed that Compritol ATO 888 is potent sustained release polymer and released only 72.45% in 24 h even at 1:1 proportion. So, lactose was added as release liner in further study which helped in achieving complete release in 24 h. Conclusion: The present study has concluded that Compritol ATO 888 can be used as matrix-forming agent to control the release of a highly water soluble drug such as Eperisone HCl. It was also observed that melt granulation technique was found more effective. Release liner like lactose may help enhancing the release profile when it is marginally slow. Keywords: - Eperisone Hydrochloride, Compritol ATO 888, Sustained release, Melt granulation, Release liner

Studies on biological macromolecules lipid-Gelucire based gastroretentive multiparticulate

Studies on biological macromolecules lipid-Gelucire based sustained release gastroretentive multiparticulates of metformin hydrochloride (MH) were developed by dispersing MH in melted Gelucire 39/01 and 43/01 using the melt granulation technique while fast release solid dispersions gastroretentive multiparticulates of glibenclamide (GLB), poorly soluble drug were developed using Gelucire 50/13 and PEG 200, 400, 4000, 6000 as carrier at different ratios. Percent drug entrapment of MH was 99.6±0.35% and in vitro floating ability was 11.3±0.47h. Model dependent analysis shows that zero order kinetics was followed while drug release mechanism was anomalous diffusion controlled. Combination of ethylcellulose, methylcellulose and microcrystalline cellulose with Gelucire were explored for release of drug, floatability and consistency for optimized formulation. While GLB multiparticulates showed entrapment efficiency of 99.8±0.11%, in vitro buoyancy for 11±0.2h and improved solubility and dissolution rate. Zero order kinetics was promising for all formulations. Model independent analysis f2 value for GIV was 40 while for M II was 54. Characterization was done by SEM, FTIR and PXRD. RP-HPLC method was adopted for simultaneous pharmacokinetic analysis of the drugs in rat plasma. In IVIVC studies confirm increased bioavailability of drugs in combination form and followed level A correlation using the diabetic type II Wistar rat.

Formulation and evaluation of sustained release venlafaxine tablets using hydrophilic-hydrophobic polymer combinations by melt granulation

The current research aims to formulate Venlafaxine Sustained Release (VHL-SR) tablets using hydrophilic-hydrophobic polymers combination blends by melt granulation technique which highlights the novelty. The polymers selected for the present study have matrix forming properties. Results of FTIR studies have shown that there were no interactions between the polymers used and the drug VHL. Various formulations of VHL- SR tablets (F1-F16) using different combinations of hydrophilic and hydrophobic polymers viz. Carbopol 71G, HPMC K15M, PEO, sodium CMC, Eudragit RS100 and precirol were formulated. Prior preformulation studies carried out on powder blend showed good flow properties. Routine quality evaluations of the VHL-SR tablets showed the diameter of the tablets of all formulations were found to be 9.0±0.0 mm and thickness ranged between 2.08±0.08 to 2.25±0.14 mm, hardness 4.08±0.20 - 5.50±0.31 kg/cm2 , percentage friability 0.24±0.03 - 0.45±0.01%, weight variation from 0-1.15%, drug content uniformity from 98.17±0.68 to 101.89±0.73%, all within Pharmacoepial limits. Results of in-vitro drug release study indicated that the formulation containing Carbopol 71G (50 mg), Xanthan gum (75 mg) and MCC (50 mg) extended the release of the VHL. Formulation F15 was the optimized one which gave satisfactory release (95.2%) for 16 hr and with a similarity factor (f2) 68.46, the release kinetics best explained by the Korsmeyer-peppas and Higuchi diffusion models. The “N” values between 0.5-1.0 in all the formulations exhibiting a non-Fickian release behavior controlled by a combination of diffusion and chain relaxation mechanism. The formulation showed appreciable stability under accelerated conditions after 2 m.

Development and Evaluation of Taste Masked Granular Formulation of Satranidazole by Melt Granulation Technique.

Drugs from nitroimidazole category are generally bitter in taste. Oral formulation with bitter taste is not palatable. Geriatrics and pediatrics patients usually suffer from swallowing difficulties. Many other patients in some disease conditions avoid swallowing tablets. Satranidazole is a new nitro-imidazole derivative with bitter taste and is available in market as film coated tablet. The purpose of this research was to mask the bitter taste of Satranidazole by coating complexation with low melting point wax and Eudragit EPO. Different types of wax (glyceryl monostearate, stearic acid and cetyl alcohol) were tried for taste masking. The drug to stearic acid ratio 1 : 2 was found to be optimum on the basis of taste evaluation and in vitro release. The formulated granules were found to possess good flow property. FTIR studies confirmed that there was no interaction between drug and excipients. Scanning Electron Microscopy of drug and the optimized batch of granules was performed. The in vitro release of drug from granules was compared with marketed tablet formulation. The taste masked granules of optimized batch showed 87.65% release of drug in 1 hr which is comparable to that of marketed tablet formulation.

Design and characterization of cefuroxime axetil biphasic floating minitablets

Biphasic floating minitablets of cefuroxime axetil were prepared by melt granulation technique using two different grades of gelucire namely 50/13 and 43/01 to maintain constant plasma drug concentration. Loading dose of cefuroxime axetil was formulated as immediate release (IR) minitablets by using hydrophilic grade of gelucire 50/13. Maintenance dose was formulated as floating sustained release (SR) minitablets by using hydrophobic grade of gelucire 43/01. The prepared IR and SR granules were subjected to micromeritic studies and scanning electron microscopy. Fourier transform infrared spectroscopy (FT-IR) study revealed that drug and selected carriers were compatible. In vitro dissolution study of optimized IR minitablets showed more than 85% of loading dose dissolved within 30 min. Optimized SR minitablets showed zero lag time with floating duration more than 12 h. The drug release from SR minitablets was linear with square root of time with non-Fickian diffusion-controlled release. The optimized batch of minitablets was filled into 0 size hard gelatin capsule. In vitro dissolution study for capsule showed an immediate burst release followed by SR up to 12 h. There is no significant change in dissolution data after storage at 40 °C and 75% RH for three months. Microbiological assay of dissolution samples of optimized minitablets filled in capsules showed proportionate increase in inhibition of growth against Escherichia coli up to 12 h samples. In vivo bioavailability study in albino rabbits showed three times improvement in oral bioavailability.

FORMULATION AND EVALUATION OF SUSTAINED RELEASE TABLET OF DILTIAZEM HYDROCHLORIDE BY MELT GRANULATION TECHNOLOGY

The objective behind present study was to formulate and evaluate sustained release tablet of Diltiazem hydrochloride by using different polymers by melt granulation technology and to study the effect of various con centrations of polymers on release rate from tablet. T ablets were prepared using bees wax, carnauba wax, paraffin wa x as release ratardent polymers . The drug and excipient compatibility study was done by FTIR method using KBr pellet method . The granules pr epared by melt granulation technique evaluated for charac terization such as bulk density , tapped density, hausners ratio, angle of repose , cars index all granules shows good flow property. The tablet of Diltiazem HCL evaluated for characterizati on such as hardness, friability , weight variation and content uniformity all tablets shows sufficient hardness and friability shows that tablets are having sufficient strength . All results were satisfactory. The in vitro drug release studies for the prepared formulat ion were conducted for a period of 12 h using an EDT 08LX dissolution tester USP Type - II apparatus (rotating paddle) set at 100 rpm and a temperature of 37 ± 0.5°C formulation was placed in the 900 ml of the medium. For first 2 h tablet was placed in 1.2 pH acidic medium which was replaced with 7.4 pH phosp hate buffer for remaining 10 h . From the dissolution study and comparative graph it was concluded that increase in concentration of wax shows decrease in drug release from tablet. Batch F3 shows 99.84 % drug release at 12 h . In vitro release data of optimized formulations (Batch F3) was fitted to various kinetic models like zero order, first o rder, Higuchi, korsmeyer - peppas and pass Higuchi model as it has highest r 2

DESIGN AND IN VITRO EVALUATION STUDIES OF DICLOFENAC SODIUM FLOATING MATRIX TABLETS BY MELT GRANULATION TECHNIQUE

The p urpose of this study was to formulate diclofenac sodium floating matrix drug de livery system by melt granulation technique . These tablets wer e developed to prolong gastric residence time and increase its bio availability. Th e diclofenac sodium tablets of 1 00 mg were developed by using different bees wax combinations which are prepared by melt granulation technique by using polymers such as Hydroxy propyl methyl cellulose(HPMC K15M), ethyl cellulose, bees wax alone or in combination with cetyl alcohol , sodium bicarbonate as a gas generating agent and other sta ndard excipients. The prepared granules are subjected to pre compression studies such as angle of repose, bulk density, tapped density, compressibility inde x , Hausner’s ratio. The optimized formulation pr oduced monolithic tablets with optimum hardness, uniform thickness, consistent weight uniformity and low friability. The results of dissolution studies, floating lag tim e indicates that formulations F6 exhibited good and controlled drug release . Key word s: Diclofenac sodium, Melt granulation, Dissolution, 0.1N HCl

Chronotherapeutic Drug Delivery from Indomethacin Compression Coated Tablets for Early Morning Pain Associated Rheumatoid Arthritis

As the main intent of delivering maximum concentration of drug available from the dosage form, an oral compression coated tablet (CCT) was intended to develop with a predetermined lag time of 6 hrs before immediate release of drug to target circadian rhythms of rheumatoid arthritis. Solid dispersions are promising approach to enhance drug release, which later will be developed as core tablet formulation and compression coated with polyethylene oxide (PEO WSR 303). Solid dispersions were formulated with different ratio of drug and carrier (sucrose fatty acid esters 1811) using solvent evaporation and melt granulation technique, optimized solid dispersion was formulated as core tablet with different diluents. Optimized core tablet was compression coated with PEO WSR 303 along with a channeling agent (DCL 21, mannitol, HPMC 5 cps and starch 1500). Lag time before immediate release of drug was markedly dependent on weight ratios of polymer and channeling agent used, which ranged from 4 to 12 hrs. Optimized solid dispersion (S9) was used for formulating optimized core tablet formulation (C8). CCT (T8) prepared with core tablet (C8) along with mannitol provided a lag time of 6 hrs with minimum concentration of channeling agent used, which was also supported from the permeability study results. Incompatibility and characterization was confirmed from DSC, XRD, FTIR and SEM studies. Unaltered Cmax and AUC0-t but delayed Tmax following oral ingestion of optimized formulation (T8) to human volunteers indicated clear lag time before immediate release of drug, which is suitable for treating rheumatoid arthritis following circadian rhythm.