The Effect of Compaction Force and Type of Pregelatinized Starch on the Dissolution of Acetaminophen

The influence of four pregelatinized starches—National® 1551, Lycatabps, Pregeflo®M, and Starch 1500®—as binders, on the dissolution of acetaminophen was evaluated in a model wet-granulated system. Systems containing 82% acetaminophen were prepared under the same processing conditions and compacted to three target tablet thicknesses. The dissolution performance was assessed using a point estimate of percent dissolved at 30 min (%T₃₀) as well as dissolution eflciency through 30 min (DE₃₀). All four binders evaluated meet USP requirements for purity. National 1551, Lycatab PGS, and Starch 1500 were not affected by compaction force in terms of dissolution performance. Differences were observed between the fully pregelatinized systems of National 1551 and Lycatab PGS, in comparison to the partially pregelatinized system, Starch 1500. The Pregeflo M starch produced a system with delayed drug dissolution and was influenced by compaction force.     

Effects of Temperature,Humidity, and Aging on the Disintegration and Dissolution of Acetaminophen Tablets

Abstract

The effect of storage for 8 weeks at 40°C in moderate and high humidity on acetaminophen tablets prepared by the wet granulation method using povidone or pregelatinized starch as a binder was studies. Storage at 52% relative humidity produced an increase in hardness of acetaminophen tablets and storage at 94% relative humidity caused a decrease in hardness. In all cases tablets granulated with pregelatinized starch were less susceptible to change caused by humidity than tablets granulated with povidone. The disintegration of tablets containing starch or povidone was slowed as the humidity was increased. Tablets stored at 40 =C and 94 V. relative humidity showed a substantial slowing of dissolution, but there was little change of dissolution of tablets when aged at 40 -C / 52% relative humidity. In comparing starch and povidone as binders, acetaminophen tablets prepared with pregelatinized starch were less effected by high humidity than tablets prepared with povidone.     

Effectiveness of Binders in Wet Granulation: A Comparison Using Model Formulations of Different Tabletability

Based on an analysis of model granulates and tablets, a comparison was made of the effectiveness of the binders PVP K30 PH, Cellulose HP-M 603, Lycatab DSH, Lycatab PGS, and L-HPC (type LH 11). A high shear mixer was used to prepare two model granulates (placebo and paracetamol) under processing conditions which were, as far as possible, comparable. The binders were added as proportions of 2%, 6%, and 10%. Water was used as the granulating liquid. The properties of the placebo granulates (particle size distribution, bulk and tapped density, granule strength, flow properties), and those of the tablets (crushing strength, friability) prepared from these granulates under different compaction forces, were generally good. However, with PVP, Cellulose HP-M603, and Lycatab, the disintegration time of the tablets did not meet pharmacopoeial requirements even though a “disintegrant” was used in the “outer phase.” The paracetamol formulations were prime examples of high-dose drug substances with particularly poor granulating and tabletting properties, well suited to reveal differences between the binders. The paracetamol granulates were of higher friability and less flowability than the placebo granulates. The tablets tended to cap, friability was (with few exceptions) high, and disintegration times were long. In the preparation of model tablets containing paracetamol, PVP K30 PH (6%). and Cellulose HP-M 603 (6%) turn out to be the binders of choice with respect to crushing strength, but the disintegration times are too long. Lycatab PGS, Lycatab DSH, and L-HPC-LH 11 could not be used to produce paracetamol tablets that met the requirements.     

A study of the compaction process and the properties of tablets made of a new co-processed starch excipient

This article deals with the study of the energetic relationships during compaction and the properties of tablets produced from a co-processed excipient based on starch and called StarCap1500^®. This article compares it with the substance Starch1500^®. The study also includes the mixtures of StarCap 1500^® and the granulated directly compressible lactose Pharmatose DCL^®15. The tablet properties tested included tensile strength and disintegration time, examined in dependence on compression force, and also a 0.4% addition of magnesium stearate. The results show a better compressibility of StarCap 1500 in comparison with Starch 1500 and a lower elastic component of energy. The tablets were stronger and disintegrated more rapidly, but the substance possessed a higher sensitivity to an addition of a lubricant than Starch 1500. Increasing portions of StarCap 1500 in the mixtures with Pharmatose DCL 15 increased the tensile strength of tablets, disintegration period as well as the sensitivity to an addition of a lubricant. From the energetic viewpoint, energy for friction was decreasing, while the energy accumulated by the tablet during compaction and the elastic component of energy were increased.     

Directly Compressible Acetaminophen Compositions Prepared by Fluidized-Bed Granulation

Abstract

Polyvinylpyrrolidone (PVP) in aqueous solution was used as a binding agent in a fluidized-bed system to agglomerate acetaminophen powder into directly compressible granules. It was found that a minimal amount of 5% w/w PVP in a concentration of 7.5% w/v or less was needed to produce granules with an acceptable flow and the corresponding tablets having enough hardness without capping. There was a strong correlation between the time for 80% dissolved (T₈₀) and the logarithm of granule volume-surface mean diameter. A directly compressible acetaminophen composition to manufacture tablets having a T₈₀ value less than 30 min can be prepared simply by adding an appropriate amount of disintegrant (crospovidone, sodium starch glycolate, or pregelatinized starch) to the agglomerated granules.     

Binder effectiveness for beads with high drug levels

Abstract

Previous reports from these laboratories showed that microcrystalline cellulose (Avicel^R MCC, PH-101) formulations with low and medium drug levels (10 and 50%) produced very uniform beads whereas formulations containing MCC with high drug levels (80%) were difficult to process without special treatment or required the incorporation of alternate excipients. In this study, several binders, at a 2% level, specifically: Carbomer (Carbopol^R 934-P), Sodium carboxymethylcellulose (CMC 7MF), Hydroxypropylcellulose (Klucel^R HXF), Methylcellulose (Methocel^R K-15). Povidone, USP (PVP K29-32) and Pregelatinized starch NF (Starch 1500^R), were evaluated to determine whether they might impart advantages in processing and whether any differences in dissolution behavior would result. Spheres containing 80% anhydrous theophylline, the binders and MCC were manufactured by the extrusion/marumerization technique. In general, beads containing high drug levels produced with these binders are suitable for further processing (coating). Processing ease, bead shape, and bead hardness (friability) varied with the choice of binder. Beads with carbomer, hydroxypropylcellulose, and methylcellulose remained intact during dissolution testing; beads with starch, carboxymethylcellulose, PVP, and the control did not.     

An Evaluation of Smecta as a Tablet Disintegrant and Dissolution Aid

Abstract

Smecta is a nonfibrous Attapulgite (NFA), mostly composed of smectite. It was evaluated as a disintegrant in tablets made by direct compression as well as by wet granulation and using lactose and dicalcium phosphate as water soluble and water insoluble fillers, respectively. An inorganic clay, magnesium aluminum silicate (Veegum), a modified starch (Starch 1500), a cross-linked carboxymethyl cellulose (Ac-Di-Sol), and a cross-linked polyvinylpyrrolidone (Polyplasdone XL) were used for comparative evaluation. Smecta performed well as a disintegrant in tablets made by either method. It was superior to Veegum and Starch 1500, but inferior to Ac-Di-Sol and Polyplasdone XL. In tablets with Smecta, dissolution of hydrochlorothiazide (HCTZ) was superior to those with Ac-Di-Sol.     

Comparative evaluation of soy polysaccharide as direct compression excipient

Abstract

Commercial soy polysaccharide (Emcosoy^R) has been evaluated as direct compression excipient in comparison with two frequently used materials, microcrystalline cellulose (Avicel pH 101) and pregelatinized maize starch (Sta-RX 1500).

Moisture sorption and desorption data analysed according to the Young and Nelson and the GAB equations and mechanical properties such as tensile strength, brittle fracture probensity, interparticle bonding isotropy and yield pressure of compacted excipients after storage at various environmental relative humidities are reported. Tableting characteristics such as punch force ratio, weight variation, tensile strength, friability, capping tendency, disintegration and dissolution of mixtures of the excipients and paracetamol are compared.

Emcosoy has been found to behave like Avicel as direct compression binder but like Sta-RX as disintegrant.     

Evaluation of Different Fast Melting Disintegrants by Means of a Central Composite Design

Fast-disintegration technologies have encountered increased interest from industries in the past decades. In order to orientate the formulators to the choice of the best disintegrating agent, the most common disintegrants were selected and their ability to quickly disintegrate direct compressed tablets was evaluated. For this study, a central composite design was used. The main factors included were the concentration of disintegrant (X₁) and the compression force (X₂). These factors were studied for tablets containing either Zeparox® or Pearlitol 200® as soluble diluents and six different disintegrants: L-HPC® LH11 and LH31, Lycatab PGS®, Vivasol®, Kollidon CL®, and Explotab®. Their micromeritics properties were previously determined. The response variables were disintegration time (Y₁), tensile strength (Y₂), and porosity (Y₃). Whatever the diluent, the longest disintegration time is obtained with Vivasol® as the disintegrant, while Kollidon CL® leads to the shortest disintegration times. Exception for Lycatab PGS® and L-HPC LH11®, formulations with Pearlitol 200® disintegrate faster. Almost the same results are obtained with porosity: no relevant effect of disintegrant concentration is observed, since porosity is mainly correlated to the compression force. In particular, highest values are obtained with Zeparox® as the diluent when compared to Pearlitol 200® and, as the type of disintegrant is concerned, no difference is observed. Tensile strength models have been all statistically validated and are all highly dependent on the compression force. Lycatab PGS® concentration does not affect disintegration time, mainly increased by the increase of compression pressure. When Pearlitol 200® is used with Vivasol®, disintegration time is more influenced by the disintegrant concentration than by the compression pressure, an increase in concentration leading to a significant and relevant increase of the disintegration time. With Zeparox®, the interaction between the two controlled variables is more complex: there is no effect of compression force on the disintegration time for a small amount of disintegrant, but a significant increase for higher concentrations. With Kollidon CL®, the main factor influencing the disintegration time is the compression force, rather than the disintegrant concentration. Increasing both the compression force and the disintegrant concentration leads to an increase of the disintegration time.For lower Kollidon CL® percentages, the compression pressure increases dramatically the tablet disintegration. With the Explotab®, whatever the increase of compression force, the disintegrant concentration leads to an increase of the disintegration time. According to Student's t-test, only the compression force significantly and strongly influences the disintegration time when Pearlitol 200® is used. A slight interaction and some trends nevertheless appear: above 150 MPa, increasing the disintegrant concentration leads to a shortened disintegration time, below this limit the opposite effect is observed.     

Influence of Compacted Hydrophobic and Hydrophilic Colloidal Silicon Dioxide on Tableting Properties of Pharmaceutical Excipients

The effect of noncompacted and compacted hydrophilic as well as hydrophobic colloidal silicon dioxide (CSD) on tableting properties of three different pharmaceutical excipients used for direct compression, namely, Avicel® PH 101, Starch 1500®®, and Tablettose® 80, was investigated. Binary powder mixtures containing 0.5% CSD and 99.5% excipient were compressed on an instrumented single-punch tablet press, and the radial tensile strength/compaction load profiles were examined. The Ryshkewitch-Duckworth relationship shows that the influence of CSD on tablet strength was dependent on the hydrophobic and hydrophilic nature of the CSD and on the compaction characteristics of the excipients. Tablets from each excipient with and without CSDs were subjected to different levels of relative humidity at 20°C for 7 days. The sorption isotherms and the radial tensile strengths of the tablets after the storage period showed that neither hydrophilic nor hydrophobic CSD influenced the tablet properties of Avicel® PH 101, Starch 1500®®, and Tablettose® 80. Moreover, ternary powder mixtures containing magnesium stearate as a third component were compressed in order to study the influence of CSD on the deleterious effect of magnesium stearate on the interparticle bonding. The radial tensile strength/compaction load profiles and the residual and ejection forces of tablets made from ternary mixtures showed that CSD eliminated the negative effect of magnesium stearate on interparticle bonding while maintaining the lubrication action, in a manner that was affected by its hydrophobicity/hydrophilicity and by the particle deformation properties of the excipient upon compression.     

The development of carbamazepine-succinic acid cocrystal tablet formulations with improved in vitro and in vivo performance

Abstract

The use of soluble cocrystal for delivering drugs with low solubility, although a potentially effective approach, often suffers the problem of rapid disproportionation during dissolution, which negates the solubility advantages offered by the cocrystal. This necessitates their robust stabilization in order for successful use in a tablet dosage form. The cocrystal between carbamezepine and succinic acid (CBZ-SUC) exhibits a higher aqueous solubility than its dihydrate, which is the stable form of CBZ in water. Using this model system, we demonstrate an efficient and material-sparing tablet formulation screening approach enabled by intrinsic dissolution rate measurements. Three tablet formulations capable of stabilizing the cocrystal both under accelerated condition of 40?°C and 75% RH and during dissolution were developed using three different polymers, Soluplus® (F₁), Kollidon VA/64 (F₂) and Hydroxypropyl methyl cellulose acetate succinate (F₃). When compared to a marketed product, Epitol® 200?mg tablets (F₀), drug release after 60?min from formulations F₁ (～82%), F₂ (～95%) and F₃ (～95%) was all higher than that from Epitol® (79%) in a modified simulated intestinal fluid. Studies in albino rabbits show correspondingly better bioavailability of F₁–F₃ than Epitol.     

The influence of tablet density on the human oral absorption of sustained release acetaminophen matrix tablets

Abstract

Low density bilayer compressed matrix tablets of acetaminophen were tested for in vitro dissolution and in vivo oral absorption. The upper layer contained a carbon dioxide-generating blend and the lower layer contained hydroxypropyl methylcellulose (HPMC) and acetaminophen. Carbon dioxide liberated by the action of the acidic dissolution medium on the upper layer is entrapped in the gelled hydrocolloid, providing buoyancy of the tablet and sustained release of the drug. For comparative purposes, similar but non-gas generating bilayer compressed matrix tablets were formulated and tested in vitro under the same conditions. These high density tablets were found to yield similar dissolution profiles as the low density tablets. The absorption characteristics of the bilayer compressed matrix tablets were compared with those of rapidly disintegrating acetaminophen tablets (TYLENOL® tablets, 500 mg) under fasted and fed conditions in six healthy subjects. Under fasted conditions, saliva profiles showed a rapid absorption for TYLENOL tablets but slower absorption for both compressed matrix tablets. Saliva profiles of TYLENOL® tablets under fed conditions were similar to those for the fasted case. In contrast, the peak saliva levels of acetaminophen for both compressed matrix tablets were significantly increased under fed conditions. The time to maximum saliva concentrations (Tmax) of all three dosage forms was not significantly affected by food intake. The relative bioavailability of the low density tablets under fasted and fed conditions was not significantly different from those of TYLENOL tablets, but vas significantly greater than that of high density tablets under fasted and fed conditions. A possibility exists that the buoyancy mechanism enabled the tablet to maintain more prolonged residence time in the gastrointestinal tract.     

Processing of Nimesulide-PEG 400-PG-PVP Solid Dispersions: Preparation,Characterization, and In Vitro Dissolution

Abstract

The objective of this investigation was to study the influence of dissolution enhancers such as polyethylene glycol 400, propylene glycol, polyvinylpyrrolidone K30, sodium lauryl sulfate, and Tween 80 on in vitro dissolution of a model active pharmaceutical material—nimesulide. Preliminary studies were conducted using a physical blend of nimesulide, and the adjuvants and solid dispersions were prepared using solvent evaporation and cogrinding methods. Aqueous solution of adjuvants was first triturated with nimesulide, followed by mixing with lactose and microcrystalline cellulose, and finally water was evaporated under vacuum in a cogrinding method. A 3³ factorial design was adopted in a cogrinding method using the concentration of polyethylene glycol 400, propylene glycol, and polyvinylpyrrolidone K30 as independent variables. Tween 80 and sodium lauryl sulfate were added in all the batches. Full and reduced models were evolved for different dependent variables. The reduced models were validated using two checkpoints. Angle of repose <35°, percentage of drug released in 30 min (Q₃₀)>40%, 45 min (Q₄₅)>50%, and 120 min (Q₁₂₀)>60% were used as constraints for the selection of an optimized batch. Contour plots are presented for the selected dependent variables. Polyvinylpyrrolidone was found to be more effective in increasing the drug dissolution, compared with polyethylene glycol 400 and propylene glycol. The granule flow was adversely affected when high levels of liquid adjuvants were used in formulations. Wettability study was conducted to measure wetting time for pure drug and the optimized batch. Improved drug dissolution was attributed to improved wetting and the solubilizing effect of adjuvants from the pseudosolid dispersions of nimesulide. Significant improvement in drug dissolution was observed (Q₁₂₀ = 70%), compared with pure drug powder (Q₁₂₀ = 15%). In conclusion, dissolution of nimesulide can be modulated using an appropriate blend of pharmaceutical adjuvants.     

Application of Flow-Through Dissolution Method for the Evaluation of Oral Formulations of Nifedipine

Abstract

The drug release characteristics of three oral formulations (one conventional and 2 extended-release) of nifedipine were evaluated using a flow-through apparatus. The experiments were conducted for 4 to 24 hours using water or phosphate buffer (0.05 or 0.1 M; pH 7.4) with or without solubilizing agent, Tween, as a dissolution medium at a flow rate of 12.5 mL/min. The drug concentrations were determined using an HPLC method based on ratios of peak heights corresponding to UV absorbances at 254 nm for nifedipine and nitrendipine (internal standard). Dissolution characteristics in various media correspond to the nifedipine solubility in the medium. Peak nifedipine concentrations with 0.05 M phosphate buffer containing 0.5% Tween were significantly higher than those in the medium without Tween (21.5±1.0 vs 8.3±0.2 μg/mL, p c 0.001). Using a 0.05 M phosphate buffer with no Tween, the products tested showed distinct dissolution profiles representative of the respective formulation type. The conventional release product (10 mg) showed a higher mean peak nifedipine concentration (C_max,d) of 49.5±2.4 pg/mL (p < 0.001) attained at (t_max,d) 0.46±0.05 h as compared to those of modified-release products. The corresponding mean values for the modified-release tablets were 8.3±0.2 and 2.6±.3 μg/mL for C_max,d, and 0.28±0.03 and 12.0±3.8 h for t_max,d for the 20 and 30 mg tablets, respectively. Area under the concentration-time curves (AUC_o-t,d) for the 10, 20 and 30 mg formulations were 12.3±0.4,20.5±2.6 and 32.6±3.7 μg.h/mL, respectively (p < 0.001). As the dissolution profiles are similar to those of plasmakerum drug concentrations-time profiles obtained from clinical studies, application of this dissolution method, along with the derived in vitro drug-release kinetics parameters for potential correlation with in vivo parameters are discussed. The results of this study show that, compared to the USP dissolution method using apparatus 1 or 2, the flow-through dissolution system offers a potentially better alternative to assess drug release characteristics for different types of formulations, especially for drugs of low aqueous solubility such as nifedipine.     

Effects of organic binders on the sintering of isostatically compacted zirconia powders

Certain processing-related flaws in cold isostatically pressed ceramic powder compacts may arise from the delayed burn-out of organic binders until the sintering temperature is approached, although the isostatic compaction technique usually gives a higher and much more uniform green density than the conventional die compaction technique. For the 3 mol% Y₂O₃-doped zirconia powder in which 3 wt% PEG 1500 was introduced, the sintered density and sintering shrinkage were found to decrease in a near linear manner with increasing isostatic compaction pressure. The processing-related defects were identified as intergranular pores (1–5 m). It is considered that these processing-related defects are a consequence of incomplete organic burn-out at low and intermediate temperatures in the heating-up period and the swelling of intergranular pores associated with the burn-out of residual organic binders at temperatures close to the sintering temperature. A higher calcination temperature and an extended calcination dwell time may be required to eliminate the organic residuals in the isostatically pressed ceramic powder compacts than in the conventional die-pressed samples.     

Controlled-Release Matrix of Acetaminophen-Ethylcellulose Solid Dispersion

Abstract

In this study ethylcellulose was evaluated as a carrier for preparation of prolonged release acetaminophen tablets. Solid dispersions containing three levels of ethylcellulose and acetaminophen (1:3; 1:1; 3:1) were prepared by the solvent method. Also physical mixtures at the same level of ethylcellulose and acetaminophen were prepared. Systems composed of solid dispersion or physical mixture containing the equivalent weight of 50 mg acetaminophen, Lactose fast-flo as diluent and 1% magnesium stearate as lubricant were compressed into tablets and tested for dissolution. The dissolution data showed that the drug release decreased as the level of ethylcellulose increased in the solid dispersion formulations. The drug release from tablets prepared with solid dispersion followed the diffusion controlled model for inert porous matrix, while the drug release from tablets prepared with physical mixture followed the first-order kinetic model.     

Binder effectiveness for beads with high drug levels

Previous reports from these laboratories showed that microcrystalline cellulose (Avicel^R MCC, PH-101) formulations with low and medium drug levels (10 and 50%) produced very uniform beads whereas formulations containing MCC with high drug levels (80%) were difficult to process without special treatment or required the incorporation of alternate excipients. In this study, several binders, at a 2% level, specifically: Carbomer (Carbopol^R 934-P), Sodium carboxymethylcellulose (CMC 7MF), Hydroxypropylcellulose (Klucel^R HXF), Methylcellulose (Methocel^R K-15). Povidone, USP (PVP K29-32) and Pregelatinized starch NF (Starch 1500^R), were evaluated to determine whether they might impart advantages in processing and whether any differences in dissolution behavior would result. Spheres containing 80% anhydrous theophylline, the binders and MCC were manufactured by the extrusion/marumerization technique. In general, beads containing high drug levels produced with these binders are suitable for further processing (coating). Processing ease, bead shape, and bead hardness (friability) varied with the choice of binder. Beads with carbomer, hydroxypropylcellulose, and methylcellulose remained intact during dissolution testing; beads with starch, carboxymethylcellulose, PVP, and the control did not.     

Insights into the dissolution mechanisms of detergent agglomerates: An approach to assess dissolution heterogeneity

In this work, the dissolution mechanisms of detergent agglomerates with different binders were investigated in aqueous solution. The dissolution processes of detergent agglomerates were online monitored by using in situ UV–VIS spectrophotometer and electric conductivity probe. Dissolution profiles were correlated by Weibull model to evaluate the time-dependent dissolution rate coefficient and to classify the type of dissolution rate function k_t(t). The Kullback-Leibler information distance d_K-L was proposed to assess the degree of dissolution heterogeneity. The results indicate that the sodium linear alkylbenzene sulfonates (NaLAS) and sodium carbonates (Na₂CO₃) in detergent agglomerates have different dissolution behaviors, and their dissolution rates are influenced by the type and content of binders. Moreover, detergent agglomerates using semi-solid NaLAS paste or liquid linear alkylbenzene sulfonic acid (HLAS) as binders in granulation processes follow different dissolution mechanisms in water.     

Comparative evaluation of granules made with different binders by a fluidized bed method

Granules were prepared using three different binders, pregelatinized starch (PGS), gelatin (GEL), and polyvinylpyrrolidone (K30) by a fluidized bed method. As a quantitative measurement of mechanical strength or abrasion resistance, granules were subjected to a friability test for certain periods of time, and friability indexes (FI) as a function of time were calculated. The data obtained were analyzed by applying standard mathematical models. According to the derived parameters of the logistic and Weibull models, which fit best to the data, mechanical strength of granules made with K30 was observed to be lower than that of the granules of PGS and GEL which have similar values of model parameters. Flow properties, consolidation, and compressibility behaviors of unfriabled (UFR) and friabled (FR) granules, which were selected based upon their Weibull time parameter, were investigated as comparative. The flow rate of granules decreased due to diminishing particle size depending on binder type and friability, but the values of angle of repose were within the acceptable limits. Regarding consolidation behavior, the change of relative density vs. the number of taps, i.e., packing rate for FR granules of GEL was slower than that of its UFR form, whereas FR granules of PGS and K30 showed faster change in relative density compared to their UFR forms. According to the parameters obtained from the Heckel equation, PGS and K30 were found to produce softer, more plastic and readily deformable granules than GEL, and the compressibility of their FR forms was not influenced negatively.     

Fluidized-Bed agglomeration of acetaminophen; direct compression of tablets and physiologic availability

A novel process was developed for manufacturing acetaminophen in a free-flowing, directly compressible agglomerated form, involving spray agglomeration of acetaminophen powder with polyvinylpyrrolidone (PVP) in isopropyl alcohol as a bonding agent using a fluidized-bed granulator. Agglomerates prepared with 5% PVP yielded a free-flowing and compressible material. Upon lubrication with 0.5% magnesium stearate, the material was found to be directly compressible into tablets. To improve dissolution and tableting properties, the agglomerates were compressed into tablets after blending with varying weight ratios of microcrystalline cellulose/pregelatinized starch as a filler/disintegrant combination. The final stable tablet formulation consisted of agglomerates equivalent to 325 mg of acetaminophen, 2.1 mg of magnesium stearate, and the filler/disintegrant in a weight ratio of 70:30 to yield a tablet weight of 425 mg. Physical properties and dissolution profile of these tablets were comparable to those of a commercial acetaminophen tablet. Physiologic availability calculated using the urinary excretion method indicated half-lives of 2.0, 2.1, and 2.2 hours for control (acetaminophen powder), experimental tablet, and a marketed product, respectively.