Fast Tablet Tensile Strength Prediction Based on Non-Invasive Analytics

In this paper, linkages between tablet surface roughness, tablet compression forces, material properties, and the tensile strength of tablets were studied. Pure sodium halides (NaF, NaBr, NaCl, and NaI) were chosen as model substances because of their simple and similar structure. Based on the data available in the literature and our own measurements, various models were made to predict the tensile strength of the tablets. It appeared that only three parameters—surface roughness, upper punch force, and the true density of material—were needed to predict the tensile strength of a tablet. Rather surprising was that the surface roughness alone was capable in the prediction. The used new 3D imaging method (Flash sizer) was roughly a thousand times quicker in determining tablet surface roughness than traditionally used laser profilometer. Both methods gave practically analogous results. It is finally suggested that the rapid 3D imaging can be a potential in-line PAT tool to predict mechanical properties of tablets in production.     

The suitability of disintegrating force kinetics for studying the effect of manufacturing parameters on spironolactone tablet properties

The aim of this paper was to study the effect of the granulate properties and tablet compression force on disintegrating force behavior in order to investigate the capability of the disintegrating force to characterize tablets that have the same composition but were manufactured in different conditions. Several tablets containing spironolactone in the external or internal granulated mixture of calcium carbonate and maize starch differing in particle size distribution, were prepared at 3 compression levels. The force developed by tablets during water uptake and disintegration was measured and plotted versus time. The curves obtained were analyzed by the Weibull equation in order to calculate the parameters characterizing the tablet disintegration kinetics. The disintegrating force time parameter, the maximum force developed, and the area under the curve were determined. In general, the reduction of time parameter value and/or the increase in maximum force developed corresponded to an acceleration in tablet disintegration. In addition, the area under the force curve increased in stronger tablets, monitoring in a sensitive way the tablet structural changes introduced by compression force. The results showed that the disintegrating force measurement can detect small changes in the structure of the tablet that cannot be discriminated by pharmacopoeia tests. The effect of manufacturing, in particular compression force, on tablet properties was quantified by the parameters of disintegrating force kinetics.     

Evaluation of the Performance Characteristics of Bilayer Tablets: Part II. Impact of Environmental Conditions on the Strength of Bilayer Tablets

Ambient air humidity and temperature are known to influence the mechanical strength of tablets. The objective of this work is to understand the influence of processing parameters and environmental conditions (humidity and temperature) on the strength of bilayer tablets. As part of this study, bilayer tablets were compressed with different layer ratios, dwell times, layer sequences, material properties (plastic and brittle), first and second layer forces, and lubricant concentrations. Compressed tablets were stored in stability chambers controlled at predetermined conditions (40C/45%RH, 40C/75%RH) for 1, 3, and 5 days. The axial strength of the stored tablets was measured and a statistical model was developed to determine the effects of the aforementioned factors on the strength of bilayer tablets. As part of this endeavor, a full 3 × 2⁴ factorial design was executed. Responses of the experiments were analyzed using PROC GLM of SAS (SAS Institute Inc, Cary, North Carolina, USA). A model was fit using all the responses to determine the significant interactions (p < 0.05). Results of this study indicated that storage conditions and storage time have significant impact on the strength of bilayer tablets. For Avicel–lactose and lactose–Avicel tablets, tablet strength decreased with the increasing humidity and storage time. But for lactose–lactose tablets, due to the formation of solid bridges upon storage, an increase in tablet strength was observed. Significant interactions were observed between processing parameters and storage conditions on the strength of bilayer tablets.

Electronic supplementary material

The online version of this article (doi:10.1208/s12249-012-9846-8) contains supplementary material, which is available to authorized users.KEY WORDS: axial tester, bilayer tablet, design of experiments, storage conditions, tablet strength     

Evaluation of the Performance Characteristics of Bilayer Tablets: Part I. Impact of Material Properties and Process Parameters on the Strength of Bilayer Tablets

Bilayer tableting technology has gained popularity in recent times, as bilayer tablets offer several advantages over conventional tablets. There is a dearth of knowledge on the impact of material properties and process conditions on the performance of bilayer tablets. This paper takes a statistical approach to develop a model that will determine the effect of the material properties and bilayer compression process parameters on the bonding strength and mode of breakage of bilayer tablets. Experiments were carried out at pilot scale to simulate the commercial manufacturing conditions. As part of this endeavor, a seven-factor half-fraction factorial (2⁷⁻¹) design was executed to study the effect of bilayer tablet compression process factors on the bonding strength of bilayer tablets. Factors studied in this work include: material properties (plastic and brittle), layer ratio, dwell time, layer sequence, first- and second-layer forces, and lubricant concentration. Bilayer tablets manufactured in this study were tested using the axial tester, as it considers both the interfacial and individual layer bonding strengths. Responses of the experiments were analyzed using PROC GLM of SAS (SAS Institute Inc, Cary, North Carolina). A model was fit using all the responses to determine the significant interactions (p < 0.05). The results of this study indicated that nature of materials played a critical role on the strength of bilayer compacts and also on mode of fracture. Bilayer tablets made with brittle materials in both the layers are strongest, and fracture occurred in the first layer indicating that interface is stronger than layers. Significant interactions were observed between the selected factors and these results will provide an insight into the interplay of material properties, process parameters, and lubricant concentration on the bonding strength and mode of breakage of bilayer tablets.

Electronic supplementary material

The online version of this article (doi:10.1208/s12249-012-9845-9) contains supplementary material, which is available to authorized users.KEY WORDS: axial tester, bilayer tablets, DOE, interfacial strength, process parameters     

Development and Evaluation of Ca+ 2 Ion Cross-Linked Carboxymethyl Xanthan Gum Tablet Prepared by Wet Granulation Technique

The objective of this work was to study the release behavior of prednisolone from calcium-cross-linked carboxymethyl xanthan gum (CMXG) tablets in dissolution medium having different pH values prevailing in the gastrointestinal lumen. Xanthan gum (XG) was derivatized to CMXG which was then cross-linked in situ with Ca⁺² ion during wet massing step of tablet preparation. Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry studies did not show any drug-polymer interaction although the drug underwent solid-state transformation during compression as evident from X-ray diffraction analysis. In vitro release study demonstrated that increase in the amount of Ca⁺² ion decreased the drug release, and beyond a certain amount, the drug release increased. While increase in both drug load and tablet crushing strength decreased the drug release, increase in exposure time in acid solution of pH 1.2 increased the overall release of the drug. The mechanism of drug release was non-Fickian/anomalous. The results indicated that variation in the amount of Ca⁺² ion can modulate the drug release from CMXG matrix tablets as needed.     

Influence of Compression Force on The Behavior of Mucoadhesive Buccal Tablets

The purpose of this research was to study the compression force influence on polymers, tablet behavior and drug release rate. Several tablet batches were produced by varying the compression force and by using hydroxyethyl cellulose (HEC) and Carbopol 940 in the 1:1 ratio as matrix forming polymers. All batches were characterized by DSC and X-ray analyses and in terms of swelling, ex vivo and in vivo mucoadhesive time, ex vivo mucoadhesion force, and in vitro and in vivo release. No significant excipient–excipient or excipient–drug interactions were observed in any of the batches. All the tablets hydrated quickly and their high hydration percentage showed that the compression forces used did not remarkably affect the water penetration and the polymeric chain stretching. Mucoadhesion performances and drug release were mainly influenced by compression force; its increase produced higher ex vivo and in vivo mucoadhesion and the in vitro and in vivo drug releases were seen to decrease with the increase of the compression force. However tablets fabricated by using the lowest compression force showed the best in vivo mucoadhesive time and hydrated faster when compared to the others. Tablets 4 and 5, prepared with the highest forces, caused pain during in vivo application and gave rise to irritation needing to be detached by the volunteers while tablet 1, prepared with the lowest force, gave the best results because it was able to produce the highest drug salivary concentration and no pain. All tablets exhibited an anomalous release mechanism.     

Neem Gum as a Binder in a Formulated Paracetamol Tablet with Reference to Acacia Gum BP

This study determined the physical, compressional, and binding properties of neem gum (NMG) obtained from the trunk of Azadirachta indica (A Juss) in a paracetamol tablet formulation in comparison with official Acacia gum BP (ACA). The physical and flow properties were evaluated using density parameters: porosity, Carr’s index, Hausner’s ratio, and flow rate. Compressional properties were analyzed using Heckel and Kawakita equations. The tensile strength, brittle fracture index, and crushing strength–friability/disintegration time ratio were used to evaluate the mechanical properties of paracetamol tablets while the drug release properties of the tablets were assessed using disintegration time and dissolution times. Tablet formulations containing NMG exhibited faster onset and higher amount of plastic deformation during compression than those containing ACA. Neem gum produced paracetamol tablets with lower mechanical strength; however, the tendency of the tablets to cap or laminate was lower when compared to those containing ACA. Inclusion of NMG improved the balance between binding and disintegration properties of paracetamol tablets produced than those containing ACA. Neem gum produced paracetamol tablets with lower disintegration and dissolution times than those containing ACA.     

Comparison of the Halving of Tablets Prepared with Eccentric and Rotary Tablet Presses

The aim of this study was to compare the densification of powder mixtures on eccentric and rotary tablet presses and to establish relationships with the halving properties of the resulting scored tablets. This is an important problem because the recent guidelines of EU require verification of the equal masses of tablet halves. The models of Walker, Heckel, and Kawakita were used to describe the powder densification on the two machines. The calculated parameters revealed that the shorter compression cycle of rotary machines results in poorer densification and lower tablet hardness at a given compression force. This is manifested in poorer halving properties, which are influenced mainly by the hardness. Better densification improves the halving even at lower tablet hardness. This demonstrates that these parameters can be good predictors of tablet halving properties.     

Compressional Behavior of a Mixture of Granules Containing High Load of Phyllanthus niruri Spray-Dried Extract and Granules of Adjuvants: Comparison between Eccentric and Rotary Tablet Machines

The purpose of this paper was to evaluate the compressional behavior of granules containing high load of a Phyllanthus niruri spray-dried extract in eccentric (ETM) and rotary (RTM) tablet presses. Tablets were constituted by spray-dried extract granules (SDEG, 92%), excipient granules (EXCG, 7.92%), and magnesium stearate (0.08%). SDEG was obtained by dry granulation and EXCG, composed of microcrystalline cellulose (62.9%) and sodium starch glycolate (37.1%), by wet granulation. Particle size distribution was fixed between 0.250 and 0.850 mm. Tablets did not evidence any mechanical failures, such as lamination or capping, or anomalous weight variation in either tablet machine types. Upper and lower tablet surface photomicrographs from ETM and RTM tablets showed differences in porosity and texture. Different RTM speeds suggested the visco-plastic behavior of the formulation, since, by slowing down rotation speeds, the tensile strength of the tablets increased significantly, but the porosity and disintegration time were not affected. Tablets produced in RTM showed lower friability and porosity than ETM tablets, which did not reflect on higher tensile strength. The EXCG distribution at upper and lower surfaces from ETM and RTM tablets was quantified by image analysis and evaluated through statistical methods. Spray-dried extract release was not influenced by the type of equipment or operational conditions to which the compacts were submitted. Construction and operation differences between both tablet presses influenced the final product, since tablets with similar tensile strength, made by distinct tablet machines, exhibited different quality parameters.     

Spray-Dried Cellulose Nanofibers as Novel Tablet Excipient

The purpose of this study was to evaluate the potential of cellulose nanofibers (also referred as microfibrillated cellulose, nanocellulose, nanofibrillated, or nanofibrillar cellulose) as novel tabletting material. For this purpose, physical and mechanical properties of spray-dried cellulose nanofibers (CNF) were examined, and results were compared to those of two commercial grades of microcrystalline cellulose (MCC), Avicel PH101 and Avicel PH102, which are the most commonly and widely used direct compression excipients. Chemically, MCC and CNF are almost identical, but their physical characteristics, like mechanical properties and surface-to-volume ratio, differ remarkably. The novel material was characterized with respect to bulk and tapped as well as true density, moisture content, and flow properties. Tablets made of CNF powder and its mixtures with MCC with or without paracetamol as model compound were produced by direct compression and after wet granulation. The tensile strength of the tablets made in a series of applied pressures was determined, and yield pressure values were calculated from the measurements. With CNF, both wet granulation and direct compression were successful. During tablet compression, CNF particles were less prone to permanent deformation and had less pronounced ductile characteristics. Disintegration and dissolution studies showed slightly faster drug release from direct compression tablets with CNF, while wet granulated systems did not have any significant difference.     

A Quantitative Correlation of the Effect of Density Distributions in Roller-Compacted Ribbons on the Mechanical Properties of Tablets Using Ultrasonics and X-ray Tomography

Enabling the paradigm of quality by design requires the ability to quantitatively correlate material properties and process variables to measureable product performance attributes. In this study, we show how heterogeneities in compacted ribbon densities quantitatively correlate to tablet mechanical properties. These density variations, which have been purposely modulated by internal and external lubrications, are characterized longitudinally and transversally by nondestructive ultrasonic and X-ray micro-computed tomography measurements. Subsequently, different transversal regions of the compacted ribbon are milled under the same conditions, and granules with nominally the same particle size distribution are utilized to manufacture cylindrical tablets, whose mechanical properties are further analyzed by ultrasonic measurements. We consider three different ribbon conditions: no lubrication (case 1); lubricated powder (case 2); and lubricated tooling (hopper, side sealing plates, feed screws, and rolls) (case 3). This study quantitatively reveals that variation in local densities in ribbons (for case 1) and process conditions (i.e., internal case 2 and external lubrication case 3) during roller compaction significantly affect the mechanical properties of tablets even for granules with the same particle size distribution. For case 1, the mechanical properties of tablets depend on the spatial location where granules are produced. For cases 2 and 3, the ribbon density homogeneity was improved by the use of a lubricant. It is demonstrated that the mechanical performances of tablets are decreased due to applied lubricant and work-hardening phenomenon. Moreover, we extended our study to correlate the speed of sound to the tensile strength of the tablet. It is found that the speed of sound increases with the tensile strength for the tested tablets.     

Variables Influencing Drug Release from Layered Matrix System Comprising Hydroxypropyl Methylcellulose

The purpose of this study was to prepare and evaluate layered matrix tablets of propranolol HCl containing HPMC and phytowax as matrix component using direct compression technique. Layering with this polymeric matrix could prolong the release of drug and shift the release pattern approach to zero order as described from the least square curve fitting. Increasing the amount of coating layer could apparently prolong the drug release. The longer lag time of drug release from one planar apparently when the amount of coating layer was increased. HPMC concentration and compression force did not affect the drug release from this three-layer tablet. The drug release from this three-layer tablet was influenced by hydrodynamic force. An increase in stirring rate was a corresponding increasing in the release rate. From photoimage and SEM, gel mass of HPMC was increased with time during dissolution and covered the core surface, therefore dissolved drug molecules were allowed to diffuse out from the core through the polymer network of gel layer containing the porous structure. This suggested that HPMC and phytowax could be fabricated into the layered matrix tablet exhibiting sustained drug release.     

Discrete mechanical model of lamellipodial actin network implements molecular clutch mechanism and generates arcs and microspikes

Mechanical forces, actin filament turnover, and adhesion to the extracellular environment regulate lamellipodial protrusions. Computational and mathematical models at the continuum level have been used to investigate the molecular clutch mechanism, calculating the stress profile through the lamellipodium and around focal adhesions. However, the forces and deformations of individual actin filaments have not been considered while interactions between actin networks and actin bundles is not easily accounted with such methods. We develop a filament-level model of a lamellipodial actin network undergoing retrograde flow using 3D Brownian dynamics. Retrograde flow is promoted in simulations by pushing forces from the leading edge (due to actin polymerization), pulling forces (due to molecular motors), and opposed by viscous drag in cytoplasm and focal adhesions. Simulated networks have densities similar to measurements in prior electron micrographs. Connectivity between individual actin segments is maintained by permanent and dynamic crosslinkers. Remodeling of the network occurs via the addition of single actin filaments near the leading edge and via filament bond severing. We investigated how several parameters affect the stress distribution, network deformation and retrograde flow speed. The model captures the decrease in retrograde flow upon increase of focal adhesion strength. The stress profile changes from compression to extension across the leading edge, with regions of filament bending around focal adhesions. The model reproduces the observed reduction in retrograde flow speed upon exposure to cytochalasin D, which halts actin polymerization. Changes in crosslinker concentration and dynamics, as well as in the orientation pattern of newly added filaments demonstrate the model’s ability to generate bundles of filaments perpendicular (actin arcs) or parallel (microspikes) to the protruding direction.     

Fast-disintegrating sublingual tablets: Effect of epinephrine load on tablet characteristics

The aim of this study was to evaluate the effect of increasing epinephrine load on the characteristics of fast-disintegrating sublingual tablets for the potential emergency treatment of anaphylaxis. Four tablet formulations, A, B, C, and D, containing 0%, 6%, 12%, and 24% of epinephrine bitartrate, respectively, and microcrystalline cellulose:low-substituted hydroxypropyl cellulose (9∶1), were prepared by direct compression, at a range of compression forces. Tablet weight variation, content uniformity, hardness, disintegration time, wetting time, and friability were measured for each formulation at each compression force. All 4 tablet formulations at each compression force were within the United States Pharmacopeia (USP) limits for weight variation and content uniformity. A linear increase in compression force resulted in an exponential increase in hardness for all formulations, a linear increase in disintegration and wetting times of A, and an exponential increase in disintegration and wetting times of B, C, and D. At a mean±SD hardness of ≥2.3±0.2 kg, all tablet formulations passed the USP friability test. At a mean±SD hardness of ≤3.1±0.2 kg, all tablet formulations resulted in disintegration and wetting times of <10 seconds and <30 seconds, respectively. Tablets with drug loads from 0% to 24% epinephrine can be formulated with hardness, disintegration times, and wetting times suitable for sublingual administration.     

Proniosomal Oral Tablets for Controlled Delivery and Enhanced Pharmacokinetic Properties of Acemetacin

Free-flowing proniosomal powders of acemetacin (AC) were prepared using the slurry method and maltodextrin as carrier. Positively charged proniosomes composed of 70:20:10 of Span 60/cholesterol (Chol)/stearylamine (SA), respectively, were successively compressed into tablets using direct compression method. The tablets were characterized for weight variability, friability, hardness, drug content uniformity, and dissolution properties. The in vivo evaluation of the prepared proniosomes (powder or tablet forms) after oral administration was investigated by the determination of AC and its active metabolite indomethacin (IND) in the blood of albino rabbits. Results indicated that the increase of Chol from 10% to 20% markedly reduced the efflux of the drug. Further Chol addition from 30% to 50% led to increased AC release rates. The proniosome tablets of AC showed greater hardness and disintegration time and less friability than AC plain tablets. The dissolution of proniosomal tablets indicated a lower drug release percentage compared to powdered proniosomes and AC plain tablets. The mean pharmacokinetic parameters of AC and IND from different formulations indicated increased t_1/2 and area under the curve (AUC) of both AC and IND for proniosomal tablets compared with both proniosomal powders and AC plain tablets. This study suggested the formulation of AC proniosomal powder into tablets to control and extend its pharmacologic effects.KEY WORDS: acemetacin, proniosomes, sustained-release tablet, pharmacokinetics     

Development of Push–Pull Osmotic Tablets Using Chitosan–Poly(Acrylic Acid) Interpolymer Complex as an Osmopolymer

The objectives of this study were to prepare push–pull osmotic tablets (PPOT) of felodipine using an interpolymer complex of chitosan (CS) and poly(acrylic acid) (PAA) as an osmopolymer, and to study the mechanisms of drug release from these tablets. The interpolymer complexes were prepared with different weight ratios of CS to PAA. Preparation of PPOT involved the fabrication of bilayered tablets with the drug layer, containing felodipine, polyethylene oxide, and the polymeric expansion layer, containing the CS–PAA complex. The effects of polymer ratios, type of plasticizers, and compression forces on release characteristics were investigated. It was found that drug release from PPOT exhibited zero-order kinetics and could be prolonged up to 12 or 24 h depending on the plasticizer used. PPOT using dibutyl sebacate showed a longer lag time and slower drug release than that using polyethylene glycol 400. In the case of polyethylene glycol 400, an increase in the CS proportion resulted in an increase in the drug release rate. The compression force had no effect on drug release from PPOT. Drug release was controlled by two consecutive mechanisms: an osmotic pump effect resulting in the extrusion of the drug layer from the tablet and subsequent erosion and dissolution of the extruded drug layer in the dissolution medium. The mathematical model (zero-order) related to extrusion and erosion rates for describing the mechanism of drug release showed a good correlation between predicted and observed values.     

Challenges in Detecting Magnesium Stearate Distribution in Tablets

Magnesium stearate (MS) is the most commonly used lubricant in pharmaceutical industry. During blending, MS particles form a thin layer on the surfaces of the excipient and drug particles prohibiting the bonding from forming between the particles. This hydrophobic layer decreases the tensile strength of tablets and prevents water from penetrating into the tablet restraining the disintegration and dissolution of the tablets. Although overlubrication of the powder mass during MS blending is a well-known problem, the lubricant distribution in tablets has traditionally been challenging to measure. There is currently no adequate analytical method to investigate this phenomenon. In this study, the distribution of MS in microcrystalline cellulose (MCC) tablets was investigated using three different blending scales. The crushing strength of the tablets was used as a secondary response, as its decrease is known to result from the overlubrication. In addition, coating of the MCC particles by MS in intact tablets was detected using Raman microscopic mapping. MS blending was more efficient in larger scales. Raman imaging was successfully applied to characterize MS distribution in MCC tablets despite low concentration of MS. The Raman method can provide highly valuable visual information about the proceeding of the MS blending process. However, the measuring set-up has to be carefully planned to establish reliable and reproducible results.     

Evidence-Based Nanoscopic and Molecular Framework for Excipient Functionality in Compressed Orally Disintegrating Tablets

The work investigates the adhesive/cohesive molecular and physical interactions together with nanoscopic features of commonly used orally disintegrating tablet (ODT) excipients microcrystalline cellulose (MCC) and D-mannitol. This helps to elucidate the underlying physico-chemical and mechanical mechanisms responsible for powder densification and optimum product functionality. Atomic force microscopy (AFM) contact mode analysis was performed to measure nano-adhesion forces and surface energies between excipient-drug particles (6-10 different particles per each pair). Moreover, surface topography images (100 nm²–10 µm²) and roughness data were acquired from AFM tapping mode. AFM data were related to ODT macro/microscopic properties obtained from SEM, FTIR, XRD, thermal analysis using DSC and TGA, disintegration testing, Heckel and tabletability profiles. The study results showed a good association between the adhesive molecular and physical forces of paired particles and the resultant densification mechanisms responsible for mechanical strength of tablets. MCC micro roughness was 3 times that of D-mannitol which explains the high hardness of MCC ODTs due to mechanical interlocking. Hydrogen bonding between MCC particles could not be established from both AFM and FTIR solid state investigation. On the contrary, D-mannitol produced fragile ODTs due to fragmentation of surface crystallites during compression attained from its weak crystal structure. Furthermore, AFM analysis has shown the presence of extensive micro fibril structures inhabiting nano pores which further supports the use of MCC as a disintegrant. Overall, excipients (and model drugs) showed mechanistic behaviour on the nano/micro scale that could be related to the functionality of materials on the macro scale.     

Eudragit E as excipient for production of granules and tablets from phyllanthus niruri L spray-dried extract

The aim of this study was to investigate the feasibility of using Eudragit E as a granulating agent for a spray-dried extract fromPhyllanthus niruri to obtain tablets containing a high dose of this product. The granules were developed by wet granulation and contained 2.5%, 5.0%, and 10.0% Eudragit E in the final product concentration. The tablets were produced on a single-punch tablet press by direct compression of granules using 0.5% magnesium stearate as a lubricant. The tablets were elaborated following a 2×3 factorial design, where Eudragit E concentration and compression force were the in-dependent variables, and tensile strength and the extract release of the tablets were the dependent variables. All granules showed better technological properties than the spray-dried extract, including less moisture sorption. The characteristics of the granules were directly dependent on the proportion of Eudragit E in the formulation. In general, all tablets showed high mechanical resistance with less than 1% friability, less moisture sorption, and a slower extract release profile. The Eudragit E concentration and compression force of the tablets significantly influenced both dependent variables studied. In conclusion, Eudragit E was efficient as a granulating agent for the spray-dried extract, but additional studies are needed to further optimize the formuations in order to achieve less water sorption and improve the release of the extract from the tablets. Published: April 27, 2007     

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.