Optimization Studies on Design and Evaluation of Orodispersible Pediatric Formulation of Indomethacin

In the present study, the aim was to optimize an orodispersible formulation of indomethacin using a combined approach of subliming agent and superdisintegrant. The tablets were made by non-aqueous wet granulation technique with superdisintegrant incorporated both intragranularly and extragranularly. A 2³ factorial design was used to investigate the effects amount of subliming agents namely camphor and ammonium bicarbonate and taste masking and soothening hydrophilic agent mannitol as independent variables and disintegration time and crushing strength as dependent responses. The volatilization time of eight hours at 50°C was optimized by conducting solid-state kinetic studies of optimized formulations. Optimized orodispersible tablets were evaluated for wetting time, water absorption ratio, porosity and in vitro and in vivo disintegration tests. Results show that higher levels of camphor and mannitol and a lower level of ammonium bicarbonate is desirable for orodispersion. Scanning electron microscopy (SEM) revealed the porous surface morphology and kinetic digital images substantiated the orodispersible property. Differential Scanning Calorimetry (DSC) studies exhibited physiochemical compatibility between indomethacin and various excipients used in the tablet formulation. Stability studies carried out as per ICH Q₁ A guidelines suggested the stable formulations for the tested time period of 6 months. The systematic approach of using subliming and disintegrating agents helped in achieving a stable, optimized orodispersible formulation, which could be industrially viable.     

Tablet formulation studies on nimesulide and meloxicam-cyclodextrin binary systems

The objective of this work was to develop tablet formulations of nimesulide-β-cyclodextrin (NI-β-CD) and meloxicam-γ-cyclodextrin (ME-γ-CD) binary systems. In the case of nimesulide, 3 types of binary systems—physical mixtures, kneaded systems, and coevaporated systems—were studied. In the case of meloxicam, 2 types of binary systems—physical mixtures and kneaded systems—were investigated. Both drug-CD binary systems were prepared at 1∶1 and 1∶2 molar ratio (1∶1M and 1∶2M) and used in formulation studies. The tablet formulations containing drug-CD binary systems prepared by the wet granulation and direct compression methods showed superior dissolution properties when compared with the formulations of the corresponding pure drug formulations. Overall, the dissolution properties of tablet formulations prepared by the direct compression method were superior to those of tablets prepared by the wet granulation method. Selected tablet formulations showed good stability with regard to drug content, disintegration time, hardness, and in vitro dissolution properties over 6 months at 40°C±2°C and 75% relative humidity. Published: May 11, 2007     

Tablet formulation containing meloxicam and beta-cyclodextrin: mechanical characterization and bioavailability evaluation

The purpose of this research was to evaluate beta-cyclodextrin (beta-CD) as a vehicle, either singly or in blends with lactose (spray-dried or monohydrate), for preparing a meloxicam tablet. Aqueous solubility of meloxicam in presence of beta-CD was investigated. The tablets were prepared by direct compression and wet granulation techniques. The powder blends and the granules were evaluated for angle of repose, bulk density, compressibility index, total porosity, and drug content. The tablets were subjected to thickness, diameter, weight variation test, drug content, hardness, friability, disintegration time, and in vitro dissolution studies. The effect of beta-CD on the bioavailability of meloxicam was also investigated in human volunteers using a balanced 2-way crossover study. Phase-solubility studies indicated an A(L)-type diagram with inclusion complex of 1:1 molar ratio. The powder blends and granules of all formulations showed satisfactory flow properties, compressibility, and drug content. All tablet formulations prepared by direct compression or wet granulation showed acceptable mechanical properties. The dissolution rate of meloxicam was significantly enhanced by inclusion of beta-CD in the formulations up to 30%. The mean pharmacokinetic parameters (C(max), K(e), and area under the curve [AUC](0-infinity)) were significantly increased in presence of beta-CD. These results suggest that beta-CD would facilitate the preparation of meloxicam tablets with acceptable mechanical properties using the direct compression technique as there is no important difference between tablets prepared by direct compression and those prepared by wet granulation. Also, beta-CD is particularly useful for improving the oral bioavailablity of meloxicam.     

Tablet formulation containing meloxicam and β-cyclodextrin: Mechanical characterization and bioavailability evaluation

The purpose of this research was to evaluate β-cyclodextrin (β-CD) as a vehicle, either singly or in blends with lactose (spray-dried or monohydrate), for preparing a meloxicam tablet. Aqueous solubility of meloxicam in presence of β-CD was investigated. The tablets were prepared by direct compression and wet granulation techniques. The powder blends and the granules were evaluated for angle of repose, bulk density, compressibility index, total porosity, and drug content. The tablets were subjected to thickness, diameter, weight variation test, drug content, hardness, friability, disintegration time, and in vitro dissolution studies. The effect of β-CD on the bioavailability of meloxicam was also investigated in human volunteers using a balanced 2-way crossover study. Phase-solubility studies indicated an A_L-type diagram with inclusion complex of 1∶1 molar ratio. The powder blends and granules of all formulations showed satisfactory flow properties, compressibility, and drug content. All tablet formations prepared by direct compression or wet granulation showed acceptable mechanical properties. The dissolution rate of meloxicam was significantly enhanced by inclusion of β-CD in the formulations up to 30%. The mean pharmacokinetic parameters (C_max, K_e, and area under the curve [AUC]_0−∞) were significantly increased in presence of β-CD. These results suggest that β-CD would facilitate the preparation of meloxicam tablets with acceptable mechanical properties using the direct compression technique as there is no important difference between tablets prepared by direct compression and those prepared by wet granulation. Also, β-CD is particularly useful for improving the oral bioavailablity of meloxicam.     

Formulation of controlled-release baclofen matrix tablets: Influence of some hydrophilic polymers on the release rate and in vitro evaluation

This work aims at investigating different types and levels of hydrophilic matrixing agents, including methylcellulose (MC), sodium alginate (Alg), and sodium carboxymethylcellulose (CMC), in an attempt to formulate controlled-release matrix tablets containing 25 mg baclofen. The tablets were prepared by wet granulation. Prior to compression, the prepared granules were evaluated for flow and compression characteristics. In vitro, newly formulated controlled-release tablets were compared with standard commercial tablets (Lioresal and baclofen). The excipients used in this study did not alter physicochemical properties of the drug, as tested by the thermal analysis using differential scanning calorimetry. The flow and compression characteristics of the prepared granules significantly improved by virtue of granulation process. Also, the prepared matrix tablets showed good mechanical properties (hardness and friability). MC- and Alg-based tablet formulations showed high release-retarding efficiency, and good reproducibility and stability of the drug release profiles when stored for 6 months in ambient room conditions, suggesting that MC and Alg are good candidates for preparing modified-release baclofen tablet formulations.     

Formulation design and optimization of mouth dissolve tablets of nimesulide using vacuum drying technique

The purpose of this research was to develop mouth dissolve tablets of nimesulide. Granules containing nimesulide, camphor, crospovidone, and lactose were prepared by wet granulation technique. Camphor was sublimed from the dried granules by exposure to vacuum. The porous granules were then compressed. Alternatively, tablets were first prepared percentage friability, wetting time, and disintegration time. In the investigation, a 3² full factorial design was used to investigate the joint influence of 2 formulation variables: amount of camphor and crospovidone. The results of multiple linear regression analysis revealed that for obtaining a rapidly disintegrating dosage form, tablets should be prepared using an optimum concentration of camphor and a higher percentage of crospovidone. A contour plot is also presented to graphically represent the effect of the independent variables on the disintegration time and percentage friability. A checkpoint batch was also prepared to prove the validity of the evolved mathematical model. Sublimation of camphor from tablets resulted in superior tablets as compared with the tablets prepared from granules that were exposed to vacuum. The systematic formulation approach helped in understanding the effect of formulation processing variables.     

Controlled-Release Carbamazepine Granules and Tablets Comprising Lipophilic and Hydrophilic Matrix Components

The objective of this study was to investigate the effect of lipophilic (Compritol 888 ATO) and hydrophilic components (combination of HPMC and Avicel) on the release of carbamazepine from granules and corresponding tablet. Wet granulation followed by compression was employed for preparation of granules and tablets. The matrix swelling behavior was investigated. The dissolution profiles of each formulation were compared to those of Tegretol CR tablets and the mean dissolution time (MDT), dissolution efficiency (DE %) and similarity factor (f(2) factor) were calculated. It was found that increase in the concentration of HPMC results in reduction in the release rate from granules and achievement of zero-order is difficult from the granules. The amount of HPMC plays a dominant role for the drug release. The release mechanism of CBZ from matrix tablet formulations follows non-Fickian diffusion shifting to case II by the increase of HPMC content, indicating significant contribution of erosion. Increasing in drug loading resulted in acceleration of the drug release and in anomalous controlled-release mechanism due to delayed hydration of the tablets. These results suggest that wet granulation followed by compression could be a suitable method to formulate sustained release CBZ tablets.     

Formulation and optimization of mouth dissolve tablets containing rofecoxib solid dispersion

The purpose of the present investigation was to increase the solubility and dissolution rate of rofecoxib by the preparation of its solid dispersion with polyvinyl pyrrolidone K30 (PVP K30) using solvent evaporation method. Drug-polymer interactions were investigated using differential scanning calorimetry (DSC), x-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). For the preparation of rofecoxib mouth dissolve tablets, its 1∶9 solid dispersion with PVP K30 was used with various disintegrants and sublimable materials. In an attempt to construct a statistical model for the prediction of disintegration time and percentage friability, a 3² randomized full and reduced factorial design was used to optimize the influence of the amounts of superdisintegrant and subliming agent. The obtained results showed that dispersion of the drug in the polymer considerably enhanced the dissolution rate. The drug-to-carrier ratio was the controlling factor for dissolution improvement. FTIR spectra revealed no chemical incompatibility between the drug and PVP K30. As indicated from XRD and DSC data, rofecoxib was in the amorphous form, which explains the better dissolution rate of the drug from its solid dispersions. Concerning the optimization study, the multiple regression analysis revealed that an optimum concentration of camphor and a higher percentage of crospovidone are required for obtaining rapidly disintegrating tablets. In conclusion, this investigation demonstrated the potential of experimental design in understanding the effect of the formulation variables on the quality of mouth dissolve tablets containing solid dispersion of a hydrophobic drug.     

Rheological Characterization and Drug Release Studies of Gum Exudates of Terminalia catappa Linn

The present study was undertaken to evaluate the gum exudates of Terminalia catappa Linn. (TC gum) as a release retarding excipient in oral controlled drug delivery system. The rheological properties of TC gum were studied and different formulation techniques were used to evaluate the comparative drug release characteristics. The viscosity was found to be dependent on concentration and pH. Temperature up to 60°C did not show significant effect on viscosity. The rheological kinetics evaluated by power law, revealed the shear thinning behavior of the TC gum dispersion in water. Matrix tablets of TC gum were prepared with the model drug dextromethorphan hydrobromide (DH) by direct compression, wet granulation and solid dispersion techniques. The dissolution profiles of the matrix tablets were compared with the pure drug containing capsules using the USP Basket apparatus with 500 ml phosphate buffer of pH 6.8 as a dissolution medium. The drug release from the compressed tablets containing TC gum was comparatively sustained than pure drug containing capsules. Even though all the formulation techniques showed reduction of dissolution rate, aqueous wet granulation showed the maximum sustained release of more than 8 h. The release kinetics estimated by the power law revealed that the drug release mechanism involved in the dextromethorphan matrix is anomalous transport as indicated by the release exponent n values. Thus the study confirmed that the TC gum might be used in the controlled drug delivery system as a release-retarding polymer.     

Controlled Release Matrix Tablets of Zidovudine: Effect of Formulation Variables on the <Emphasis Type="BoldItalic">In Vitro</Emphasis> Drug Release Kinetics

The purpose of this research was to design oral controlled release (CR) matrix tablets of zidovudine (AZT) using hydroxypropyl methylcellulose (HPMC), ethyl cellulose (EC) and carbopol-971P (CP) and to study the effect of various formulation factors on in vitro drug release. Release studies were carried out using USP type 1 apparatus in 900 ml of dissolution media. Release kinetics were analyzed using zero-order, Higuchi’s square root and Ritger–Peppas’ empirical equations. Release rate decreased with increase in polymer proportion and compression force. The release rate was lesser in formulations prepared using CP (20%) as compared to HPMC (20%) as compared to EC (20%). No significant difference was observed in the effect of pH of dissolution media on drug release from formulations prepared using HPMC or EC, but significant difference was observed in CP based formulations. Decrease in agitation speed from 100 to 50 rpm decreased release rate from HPMC and CP formulations but no significant difference was observed in EC formulations. Mechanism of release was found to be dependent predominantly on diffusion of drug through the matrix than polymer relaxation incase of HPMC and EC formulations, while polymer relaxation had a dominating influence on drug release than diffusion incase of CP formulations. Designed CR tablets with pH independent drug release characteristics and an initial release of 17–25% in first hour and extending the release up to 16–20 h, can overcome the disadvantages associated with conventional tablets of AZT.     

Once-daily sustained-release matrix tablets of nicorandil: Formulation and in vitro evaluation

The objective of the present study was to develop once-daily sustained-release matrix tablets of nicorandil, a novel potassium channel opener used in cardiovascular diseases. The tablets were prepared by the wet granulation method. Ethanolic solutions of ethylcellulose (EC), Eudragit RL-100, Eudragit RS-100, and polyvinylpyrrolidone were used as granulating agents along with hydrophilic matrix materials like hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose, and sodium alginate. The granules were evaluated for angle of repose, bulk density, compressibility index, total porosity, and drug content. The tablets were subjected to thickness, diameter, weight variation test, drug content, hardness, friability, and in vitro release studies. The granules showed satisfactory flow properties, compressibility, and drug content. All the tablet formulations showed acceptable pharmacotechnical properties and complied with in-house specifications for tested parameters. According to the theoretical release profile calculation, a oncedaily sustained-release formulation should release 5.92 mg of nicorandil in 1 hour, like conventional tablets, and 3.21 mg per hour up to 24 hours. The results of dissolution studies indicated that formulation F-I (drug-to-HPMC, 1∶4; ethanol as granulating agent) could extend the drug release up to 24 hours. In the further formulation development process, F-IX (drug-to-HPMC, 1∶4; EC 4% wt/vol as granulating agent), the most successful formulation of the study, exhibited satisfactory drug release in the initial hours, and the total release pattern was very close to the theoretical release profile. All the formulations (except F-IX) exhibited diffusion-dominated drug release. The mechanism of drug release from F-IX was diffusion coupled with erosion.     

Roll Compaction and Tableting of High Loaded Metformin Formulations Using Efficient Binders

Metformin has a poor tabletability and flowability. Therefore, metformin is typically wet granulated with a binder before tableting. To save production costs, it would be desirable to implement a roll compaction/dry granulation (RCDG) process for metformin instead of using wet granulation. In order to implement RCDG, the efficiency of dry binders is crucial to ensure a high drug load and suitable properties of dry granules and tablets. This study evaluates dry granules manufactured by RCDG and subsequently tableting of high metformin content formulations (≥?87.5%). Based on previous results, fine particle grades of hydroxypropylcellulose and copovidone in different fractions were compared as dry binders. The formulations are suitable for RCDG and tableting. Furthermore, results can be connected to in-die and out-of-die compressibility analysis. The addition of 7% of dry binder is a good compromise to generate sufficient mechanical properties on the one hand, but also to save resources and ensure a high metformin content on the other hand. Hydroxypropylcellulose was more efficient in terms of granule size, tensile strength and friability. Three percent croscarmellose was added to reach the specifications of the US Pharmacopeia regarding dissolution. The final formulation has a metformin content of 87.5%. A loss in tabletability does not occur for granules compressed at different specific compaction forces, which displays a robust tensile strength of tablets independent of the granulation process.     

Preparation and assessment of novel coprocessed superdisintegrant consisting of crospovidone and sodium starch glycolate: A technical note

Summary and Conclusion  Coprocessed superdisintegrant consisting of crospovidone and SSG exhibited good flow and compression characteristics. Cefixime trihydrate and ibuprofen tablets containing coprocessed superdisintegrant exhibited quick disintegration and improved drug dissolution. Publshed: February 2, 2007     

The Influence of the API Properties on the ODTs Manufacturing from Co-processed Excipient Systems

Directly compressible co-processed excipient systems facilitate orodispersible tablets (ODTs) manufacturing. Despite several excipient systems available, it is reported that the incorporation of high drug dose into the tablet mass may negatively affect both disintegration and mechanical properties. Therefore the influence of drug properties on the quality of orodispersible tablets was investigated. Fast dissolving tablet matrix was made of a co-processed excipient system F-Melt. Two grades of F-Melt that differed in composition, particle shape, and specific surface area were used to form tablet matrix. Ibuprofen, diclofenac sodium, and diltiazem hydrochloride were chosen as model drugs of different physicochemical properties such as solubility, particle size, and shape. Ninety formulations containing 12.5, 25, or 50 wt% of the model drug and F-Melt type C or M were prepared by direct compression. The quality of tablets was examined on the base of disintegration time, wetting time, mechanical resistance and texture analysis. The results showed that F-Melt grade, drug solubility, and its dose had an influence on the quality of tablets. From ninety formulations prepared, only four batches containing F-Melt type C and 12.5 wt% of ibuprofen, diclofenac sodium, or diltiazem hydrochloride could be classified as ODTs. Their disintegration time ranged from 41 to 144 s. In the case of F-Melt type M, tablets disintegrating within 101 s of friability below 1% could be prepared only if 12.5 wt% of diclofenac sodium was incorporated into the tablet mass.Key words: diclofenac sodium, diltiazem hydrochloride, direct compression, F-Melt, ibuprofen, ODTs     

Formulation, Release Characteristics and Bioavailability Study of Oral Monolithic Matrix Tablets Containing Carbamazepine

This study examined the release of carbamazepine (CBZ) from hydrophobic (Compritol 888 ATO) and hydrophilic-hydrophobic matrix combination (Compritol 888 ATO-hydroxpropyl methylcellulose, HPMC). Hydrophobic matrix tablets were prepared by hot fusion technique, while hydrophilic-hydrophobic matrix tablets were prepared by wet granulation technique. The properties of the compressed matrix tablets were determined according to the US Pharmacopoeia. Both matrix formulations displayed a controlled-release profile when compared to the reference formulation (Tegretol CR 200). The bioavailability of CBZ formulations and Tegretol CR 200 were evaluated in beagle dogs. Carbamazepine presented a significant higher bioavailability from matrix tablets containing hydrophilic polymer (HPMC) than that obtained from Tegretol CR200. The average inter-subject plasma concentration variability CV% was the least with tablet containing hydrophilic polymer (HPMC) and was the highest with Tegretol CR 200 (33.8 and 54.1, respectively). Analysis of variance applied to log AUC(0-alpha) and log C(max) showed statistical significant differences among the three formulations (P < 0.05). Plotting the fraction of CBZ released in vitro and fraction absorbed showed a statistically significant relationship (R(2) = 0.935-0.975) for the three matrix tablets examined.     

A study on moisture isotherms of formulations: the Use of polynomial equations to predict the moisture isotherms of tablet products

The objectives of this study were to investigate the effects of manufacturing parameters on the moisture sorption isotherms of some tablet formulations and to predict the moisture isotherms of the final formulations using polynomial equations. Three tablet formulations including a placebo and 2 drug products were prepared through wet granulation, drying, compression, and coating processes. Equilibrium moisture content of excipients and granules at 25°C with different relative humidities were determined using a dynamic moisture sorption microbalance, while such data for tablets were determined using desiccators. Moisture sorption isotherms were expressed in polynomial equations. Excipient isotherms were used to predict the moisture sorption isotherms of the 3 tablet products. Results showed that different physical properties of granules and tablets, such as particle size distribution, density, and porosity resulting from different granulation and compression conditions did not have significant effect on the moisture isotherms of the materials. Changing coating materials from a powder mixture to a film also did not change the moisture sorption characteristics significantly. The predicted moisture sorption isotherms of the formulations agreed well with the experimental results. These results show that moisture isotherms of solid pharmaceutical products manufactured with conventional processes may be predicted using the isotherms of excipients, and polynomial equations may be used as a tool for the prediction of moisture isotherms.     

Difference in the Lubrication Efficiency of Bovine and Vegetable-Derived Magnesium Stearate During Tabletting

The purpose of this work was to evaluate and compare the functionality of bovine fatty acids-derived (MgSt-B) and vegetable fatty acids-derived (MgSt-V) magnesium stearate powders when used for the lubrication of granules prepared by high-shear (HSG) and fluid bed (FBG) wet granulation methods. The work included evaluation of tablet compression and ejection forces during tabletting and dissolution testing of the compressed tablets. Granules prepared by both granulation methods required significantly lower ejection force (p < 0.01) when lubricated with the MgSt-V powder as compared to those lubricated with the MgSt-B powder. Granules prepared by the HSG method and lubricated with the MgSt-V powder also required significantly lower compression force (p < 0.01) to produce tablets of similar weight and hardness as compared to those lubricated with the MgSt-B powder. The dissolution profiles were not affected by these differences and were the same for tablets prepared by same granulation method and lubricated with either magnesium stearate powder. The results indicate significant differences (p < 0.01) between lubrication efficiency of the MgSt-B and the MgSt-V powders and emphasize the importance of functionality testing of the MgSt powders to understand the impact of these differences. The opinions expressed in this work are only of authors, and do not necessarily reflect the policy and statements of the FDA.     

Preparation and Characterization of a Novel Co-processed Excipient of Chitin and Crystalline Mannitol

A co-processed excipient was prepared from commercially available crystalline mannitol and α-chitin using direct compression as well as spray, wet, and dry granulation. The effect of the ratio of the two components, percentage of lubricant and particle size, on the properties of the prepared co-processed excipient has been investigated. α-Chitin forms non-hygroscopic, highly compactable, disintegrable compacts when co-processed with crystalline mannitol. The compaction properties of the co-processed mannitol–chitin mixture were found to be dependent upon the quantity of mannitol added to chitin, in addition to the granulation procedure used. Optimal physicochemical properties of the excipient, from a manufacturing perspective, were obtained using a co-processed mannitol–chitin (2:8, w/w) mixture prepared by wet granulation (Cop-MC). Disintegration time, crushing strength, and friability of tablets, produced from Cop-MC using magnesium stearate as a lubricant, were found to be independent of the particle size of the prepared granules. The inherent binding and disintegration properties of the compressed Cop-MC are useful for the formulation of poorly compressible, high-strength, and low-strength active pharmaceutical ingredients. The ability to co-process α-chitin with crystalline mannitol allows chitin to be used as a valuable industrial pharmaceutical excipient.     

Effects of Processing on the Release Profiles of Matrix Systems Containing 5-Aminosalicylic Acid

The aim of this study was to investigate the influence of different processing methods on the profiles of 5-aminosalicylic acid dissolution from controlled-release matrix systems based on Eudragit® RL and Eudragit® RS water-insoluble polymers. The pure polymers and their mixtures were studied as matrix formers using different processing methods, i.e., direct compression, wet granulation of the active ingredient with the addition of polymer(s) to the external phase, wet granulation with water, and wet granulation with aqueous dispersions. In comparison with the directly compressed tablets, tablets made by wet granulation with water demonstrated a 6–19% increase in final drug dissolution, whereas when polymers were applied in the external phase during compression, a 0–13% decrease was observed in the amount of drug released. Wet granulation with aqueous polymer dispersions delayed the release of the drug; this was especially marked (a 54–56% decrease in drug release) in compositions, which contained a high amount of Eudragit RL 30D. The release profiles were mostly described by the Korsmeyer–Peppas model or the Hopfenberg model.KEY WORDS: controlled release, matrix tablet, polymethacrylates, release kinetics     

Development of Modified-Release Tablets of Zolpidem Tartrate by Biphasic Quick/Slow Delivery System

Zolpidem tartrate is a non-benzodiazepine analogue of imidazopyridine of sedative and hypnotic category. It has a short half-life with usual dosage regimen being 5 mg, two times a day, or 10 mg, once daily. The duration of action is considered too short in certain circumstances. Thus, it is desirable to lengthen the duration of action. The formulation design was implemented by preparing extended-release tablets of zolpidem tartrate using the biphasic delivery system technology, where sodium starch glycolate acts as a superdisintegrant in immediate-release part and hydroxypropyl methyl cellulose as a release retarding agent in extended-release core. Tablets were prepared by direct compression. Both the core and the coat contained the drug. The pre-compression blends were evaluated for angle of repose, bulk density, and compressibility index. The tablets were evaluated for thickness, hardness, weight variation test, friability, and in vitro release studies. No interaction was observed between zolpidem tartrate and excipients from the Fourier transform infrared spectroscopy and differential scanning calorimetry analysis. The results of all the formulations prepared were compared with reference product Stilnoct®. Optimized formulations showed release patterns that match the United States Pharmacopeia (USP) guidelines for zolpidem tartrate extended-release tablets. The mechanism of drug release was studied using different mathematical models, and the optimized formulation has shown Fickian diffusion. Accelerated stability studies were performed on the optimized formulation.KEY WORDS: biphasic delivery system technology, hydroxypropyl methyl cellulose, modified release, sodium starch glycolate, zolpidem tartrate