Dissolution Of Acetaminophen Research Articles

Effect of magnesium stearate solid lipid nanoparticles as a lubricant on the properties of tablets by direct compression

This study discusses the lubricant properties of magnesium stearate solid lipid nanoparticles (MgSt-SLN) and their effect on the tabletability, mechanical properties, disintegration, and acetaminophen-model dissolution time of microcrystalline cellulose (MCC) tablets prepared by direct compression. The behavior of MgSt-SLN was compared to reference material (RM) to identify advantages and drawbacks. The nanoprecipitation/ion exchange method was employed to prepare the MgSt-SLN. Particle size, zeta potential, specific surface area, morphology, and true density were measured to characterize the nanosystem. The MgSt-SLN particle sizes obtained were 240 ± 5 nm with a specific surface area of 12.2 m2/g. The MCC tablets with MgSt-SLN presented a reduction greater than 20 % in their ejection force, good tabletability, higher tensile strength, lower disintegration delay, and marked differences in acetaminophen dissolution when compared to the RM. The reduced particle size of the magnesium stearate seems to offer a promising technological advantage as an efficient lubricant process that does not affect the properties of tablets.

Effect of mono, di, tri ethanolamine lactate ionic liquids on the solubility of acetaminophen: Experimental measurement and correlation

Solubility is one of the most important physicochemical properties in the discovery and development of drugs and adding a co-solvent to an aqueous solution for further designing drug formation is the most widely used method in the pharmaceutical industry. In recent years, protic ionic liquids (PILs) as a new low-cost and an environmentally friendly class of green solvents have been used to overcome drug solubility issues. In this research work, the effect of some PILs containing 2-hydroxyethylammonium, bis(2-hydroxyethyl)ammonium, and tris(2-hydroxyethyl)ammonium cations and lactate anion have been investigated for acetaminophen (ACP) solubility at temperature ranges (298.15 to 313.15) K. The results show that ACP solubility increases with increasing PIL concentration and at higher temperatures and that PILs containing tris(2-hydroxyethyl)ammonium lactate have a greater impact on ACP solubility. The obtained solubility data were fitted by the e-NRTL and Wilson models which e-NRTL model is more consistent with experimental data. Finally, by applying the Gibbs and van't Hoff equations, the apparent dissolution thermodynamic functions such as enthalpy, Gibbs free energy, and entropy have been estimated. The results indicate that ACP dissolution processes in the investigated systems are endothermic.

Acetaminophen solubility in aqueous solutions of betaine-propylene glycol natural deep eutectic solvent at different temperatures

This work reports the aqueous solubility of acetaminophen (ACP), a most traditionally used analgesics and antipyretic drug, in betaine/propylene glycol deep eutectic solvent (Bet/PG DES) as a green solvent at temperatures ranging from 293.15 K to 313.15 K and atmospheric pressure (≈ 85 kPa). The ACP solubility in this solvent not only increases with increasing temperature, but also increases by increasing the DES portion reaching maximum values in the mixture of wDES = 0.90 at 313.15 K. The obtained experimental solubilities are accurately correlated with van’t Hoff, Jouyban-Acree, Jouyban-Acree-van’t Hoff, the modified Jouyban-Acree-van’t Hoff, the mixture response surface, the combined nearly ideal binary solvent/Redlich-Kister, the Buchowski-Ksiazczak and modified Wilson models. The accuracy of each model is evaluated by computing the average relative deviations (ARD%) and the results confirm that the the mixture response surface model (ARD% = 1.78) has a better correlation performance in comparison with the other models. Besides, thermodynamic behavior of ACP in the aqueous solution of Bet/PG DES is described with calculation of thermodynamic functions including Gibbs energy, enthalpy, and entropy of dissolution achieved from the van't Hoff and Gibbs equations. The results revealed that the ACP dissolution is an endothermic and entropy-driven process.

3D Printing and Dissolution Testing of Novel Capsule Shells for Use in Delivering Acetaminophen

Individualized drug delivery improves drug efficacy and safety for patients. To implement individualized drug delivery, patient-specific tailored dosages produced on a small scale are needed. However, current pharmaceutical manufacturing is not suitable for personalized dosage forms. Although convenient to deliver various drugs, current gelatin capsules using animal collagen protein have many limitations, such as releasing drugs too fast and incompatibility with some diets. In contrast, 3D printed capsules have great potential to advance individualized treatments. In this paper, we 3D printed and tested non-animal-based capsule shells for the delivery of acetaminophen. Capsule shells were composed of poly(vinyl) alcohol (PVA) and PVA blends with 5-25% hydroxypropyl methylcellulose (HPMC). Dissolution of acetaminophen when delivered in –hese capsule shells was tested using a USP dissolution test apparatus 2 (paddle type) at gastric pH. The novel shells were compared to each other and to commercially available hard gelatin capsules. Dissolution results show that acetaminophen when delivered in 3D printed capsules was slower than when delivered by gelatin capsules. Increasing the percentage of HPMC in the blend further delayed its release and dissolution. This delay could potentially increase the efficacy and reduce the side effects of acetaminophen. These shells also offer a non-animal-based alternative to gelatin capsules. Furthermore, 3D printing of capsule shells with specific polymer blends may be useful for patient-specific therapy in compounding pharmacies across the country.

Solubility study of acetaminophen in the mixtures of acetonitrile and water at different temperatures

Acetaminophen solubility in the mixtures of acetonitrile and water in the temperature range of 293.2–313.2 K is determined by a shake-flask method followed by spectrophotometry method. The generated data are correlated with some linear and non-linear solubility models. Furthermore, the density of saturated mixtures at different temperatures is also regressed by the Jouyban-Acree model. The accuracy of each used model is investigated by the mean relative deviations (MRD%) of the back-calculated solubility or density data. The apparent thermodynamic properties of acetaminophen dissolution, mixing and solvation in the mixtures of acetonitrile and water are also computed based on the van't Hoff and Gibbs equations. Furthermore, based on the inverse Kirkwood-Buff integrals the preferential solvation parameters of acetaminophen by acetonitrile were also calculated.

Polyethylene glycol electrolyte lavage solution increases tablet dissolution of acetaminophen in an in vitro model mimicking acute poisoning

IntroductionPolyethylene glycol electrolyte lavage solution (PEG-ELS) is similar to pharmaceutical solvent propylene glycol and used following acute poisonings for whole bowel irrigation (e.g., “body stuffing”). This raises concern of PEG-ELS increasing solubility following acute ingestions of non-sustained release xenobiotics in the stomach. We theorized PEG-ELS increases solubility of acetaminophen in an in vitro stomach model. Material and methodsAn in vitro artificial stomach with 500 mL simulated gastric fluid and either 500 mL of sodium chloride 0.9% (group A) or 500 mL of PEG-ELS (group B). Ten non-sustained release acetaminophen tablets added with concentrations 0, 15, 45 and 90 min in triplicate. Mean concentrations and mean area under the curve (AUC) (mg-min/L to 90 min). ResultsIn control group A (normal saline + simulated gastric fluid) mean acetaminophen concentrations 0, 3, 13 and 36 mg/L at 0, 15, 45 and 90 min, respectively. In group B (PEG-ELS + simulated gastric fluid) mean acetaminophen concentrations 0, 34, 109 and 136 mg/L at 0, 15, 45 and 90 min, respectively (p < 0.05). Mean AUC 0-90 1385 [95% C.I. 990.5–1779] mg-min/L in control group A compared to mean AUC 0-90 in group B (PEG-ELS) 7673 mg-min/L [95% C.I. 4832–10513] (p < 0.05). DiscussionGroup B (PEG-ELS) with significantly higher mean acetaminophen concentrations and greater mean AUC compared to control group A (normal saline). ConclusionWe demonstrated increased mean acetaminophen concentrations and increased mean AUC of following exposure of PEG-ELS in an artificial stomach model.

The Influence of Polyethylene Glycol Solution on the Dissolution Rate of Sustained Release Morphine.

Whole bowel irrigation (WBI) is a management option for overdose of medications poorly adsorbed to activated charcoal, with modified release properties, or for body packers. Polyethylene glycol (PEG) is a mixture of ethylene oxide polymers of varying molecular weight. PEG with an average molecular weight of 3350g/mol is used for WBI. PEG electrolyte lavage solution has been shown in vitro to hasten the dissolution of acetaminophen. The impact of PEG on the pharmacokinetics of extended release pharmaceuticals is unknown. Lower average molecular weight PEG mixtures are used as solvents and excipients. We sought to investigate the impact of PEG on the release of morphine from several extended release morphine formulations. An in vitro gastric model was developed. To test the validity of our model, we first investigated the previously described interaction of ethanol and Avinza®. Once demonstrated, we then investigated the effect of PEG with several extended release morphine formulations. In the validation portion of our study, we confirmed an ethanol Avinza® interaction. Subsequently, we did not observe accelerated release of morphine from Avinza® or generic extended release morphine in the presence of PEG. The use of PEG for gastric decontamination following ingestion of these extended release morphine formulations is unlikely to accelerate morphine release and aggravate intoxication.

Oral medication delivery in impaired swallowing: thickening liquid medications for safe swallowing alters dissolution characteristics

Acetaminophen (paracetamol) is available in a wide range of oral formulations designed to meet the needs of the population across the age-spectrum, but for people with impaired swallowing, i.e. dysphagia, both solid and liquid medications can be difficult to swallow without modification. The effect of a commercial polysaccharide thickener, designed to be added to fluids to promote safe swallowing by dysphagic patients, on rheology and acetaminophen dissolution was tested using crushed immediate-release tablets in water, effervescent tablets in water, elixir and suspension. The inclusion of the thickener, comprised of xanthan gum and maltodextrin, had a considerable impact on dissolution; acetaminophen release from modified medications reached 12–50% in 30 min, which did not reflect the pharmacopeia specification for immediate release preparations. Flow curves reflect the high zero-shear viscosity and the apparent yield stress of the thickened products. The weak gel nature, in combination with high G' values compared to G'' (viscoelasticity) and high apparent yield stress, impact drug release. The restriction on drug release from these formulations is not influenced by the theoretical state of the drug (dissolved or dispersed), and the approach typically used in clinical practice (mixing crushed tablets into pre-prepared thickened fluid) cannot be improved by altering the order of incorporation or mixing method.

Feasability of a new process to produce fast disintegrating pellets as novel multiparticulate dosage form for pediatric use

Novel orally disintegrating system based on multiparticulate form was developed, offering an alternative to encounter major issues in the design of dosage form for pediatric patients, i.e., the difficulty in swallowing large solid dosage form (tablet or capsule), and the requirement to cover a broad range of doses for different age groups. Microcrystalline cellulose-based pellets containing acetaminophen were prepared via extrusion/spheronization followed by freeze-drying. The in vitro disintegration behavior of these pellets was quantitatively measured with a texture analyzer. Mercury intrusion and gas adsorption techniques, scanning electron microscopy of pellet surface and cross-section were performed in order to characterize their internal porous structure. Pellets characteristics such as size distribution, sphericity, friability and drug release were also determined. The developing process was able to produce pellets containing high drug loading (25, 50 and up to 75%, w/w) with good sphericity (aspect ratio ∼1) and low friability. The pellets exhibited an instantaneous disintegration upon contact with water, which was indicated by two parameters: the disintegration onset was approximating to 0, and the disintegration time less than 5s. The fast disintegration behavior is correlated with the pellet internal structure characterized by a capillary network with pore diameter varying from 0.1 to 10μm. Such a structure not only ensured a rapid disintegration but it also offers to freeze-dried pellets adequate mechanical properties in comparison with conventional freeze-dried forms. Due to pellet disintegration, fast dissolution of acetaminophen was achieved, i.e., more than 90% of drug released within 15min. This novel multiparticulate system offers novel age-appropriate dosage form for pediatric population owing to their facility of administration (fast disintegration) and dosing flexibility (divided and reduced-size solid form).

Influence of capsule shell composition on the performance indicators of hypromellose capsule in comparison to hard gelatin capsules

The purpose of this study was to assess the in vitro performances of “vegetable” capsules in comparison to hard gelatin capsules in terms of shell weight variation, reaction to different humidity conditions, resistance to stress in the absence of moisture, powder leakage, disintegration and dissolution. Two types of capsules made of HPMC produced with (Capsule 2) or without (Capsule 3) a gelling agent and hard gelatin capsules (Capsule 1) were assessed. Shell weight variability was relatively low for all tested capsules shells. Although Capsule 1 had the highest moisture content under different humidity conditions, all capsule types were unable to protect the encapsulated hygroscopic polyvinylpyrrolidone (PVP) powder from surrounding humidity. The initial disintegration for all Capsule 1 occurred within 3 min, but for other types of capsules within 6 min (n = 18). Dissolution of acetaminophen was better when the deionized water (DIW) temperature increased from 32 to 42 °C in case of Capsule 1, but the effect of temperature was not significant for the other types of capsules. Acetaminphen dissolution from Capsule 1 was the fastest (i.e. >90% in 10 min) and independent of the media pH or contents unlike Capsule 2 which was influenced by the pH and dissolution medium contents. It is feasible to use hypromellose capsules shells with or without gelling agent for new lines of pharmaceutical products, however, there is a window for capsule shells manufacturing companies to improve the dissolution of their hypromellose capsules to match the conventional gelatin capsule shells and eventually replace them.

Dynamic and Static Characteristics of Drug Dissolution in Supercritical CO2 by Infrared Spectroscopy: Measurements of Acetaminophen Solubility in a Wide Range of State Parameters

In this work we use infrared spectroscopy to investigate solubility properties of a bioactive substance in supercritical CO2 (scCO2). By using acetaminophen as a model compound, we show that the method can provide high sensitivity that makes it possible to study solubility at small concentrations, up to 10–6 mol·L–1. This method also allows one to investigate the kinetics of the dissolution process in supercritical solvent. Our measurements at two different points of the (p,T) plane ((40 MPa, 373 K) and (40 MPa, 473 K)) have shown significant difference in the kinetic mechanisms of acetaminophen dissolution at these two states: at higher temperature the dissolution process in scCO2 has two steps: (i) “fast” step when the acetaminophen concentration in scCO2 quickly reaches (70 to 80) % of the saturation level and (ii) a subsequent “slow” step where the acetaminophen concentration slowly increases up to the saturation level. However, at lower temperature, the dissolution process has only one, “slow” step.

Combined UV/vis and micro-tomography investigation of acetaminophen dissolution from granules

The X-ray micro-tomography (micro-CT) technique has been used to visualize the microstructure of granules produced by high shear wet granulation and the dynamic evolution of porosity during granule dissolution. Using acetaminophen (paracetamol) as the active pharmaceutical ingredient (API) and microcrystalline cellulose (Avicel PH-200) as an excipient, the porosity of the granules was systematically influenced by the granulation process parameters (binder/solids ratio, impeller speed and wet massing time). An increase of granule porosity from 7% to 10% and 18% lead to a decrease of the dissolution time t90 from 435 min to 98 min and 37 min, respectively. The combination of time-resolved micro-CT imaging with UV/vis detection of the quantity dissolved made it possible to evaluate the effective diffusion coefficient of the API through the granule structure, and thus establish a quantitative structure–property relationship for dissolution. A power-law dependence of the effective diffusivity on porosity (Archie's law) was found to hold.

Synergic Effects of Polymeric Additives on Dissolution and Crystallization of Acetaminophen

To study how polymeric additives interact with the crystal surface of acetaminophen, and why they have different effects on drug crystallization and dissolution. The effects of different polymers on the etching patterns, crystallization and intrinsic dissolution rate (IDR) of acetaminophen have been studied. Some polymers have shown clear consistency in their effects on the etching patterns, crystallization and IDR of acetaminophen. For example, hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP), not only changed the etching patterns of the acetaminophen (010) face, but also inhibited acetaminophen crystallization significantly. Some polymers, like 2-hydroxyethyl cellulose (HEC), poly(vinyl alcohol) (PVA) and poly(ethylene glycol) (PEG) only had limited effects on the IDR and etching patterns, and no significant inhibitory effects on crystallization. Even though some polymeric additives have no structural similarity to acetaminophen, they still can affect dissolution and crystallization of acetaminophen due to the synergic effects of their neighboring subunits during surface adsorption. The effects of polymeric additives on crystallization and dissolution of acetaminophen are affected not only by the specific interactions between adsorbed polymer molecules and crystal surface, but also by the mobility of the functional groups involved in the specific interactions.

Dissolution of acetaminophen crystallised in the presence of polyvinylpyrrolidone

Crystallisation of acetaminophen in the presence of polyvinylpyrrolidone (PVP) caused a marked enhancement of its dissolution rate. By increasing the molecular weight and/or the concentration of PVP in the crystallisation medium, the obtained crystals exhibited faster dissolution. This enhancement was attributed to the absorption of PVP on the surface of the acetaminophen crystals, which increased their wettability. This was confirmed by measuring the contact angle between water and the acetaminophen surface. A decrease in the crystal size of acetaminophen obtained in the presence of PVP may have also contributed to the higher dissolution rate. It was shown that the solubility of untreated acetaminophen increased in solutions containing PVP. However, there was no significant difference between the solubility of untreated acetaminophen and that of samples crystallised in the presence of PVP. The amount of PVP in the acetaminophen particles was far below that required to produce a significant concentration in the dissolution medium for increasing acetaminophen solubility.

Sustained-release effect of codried excipients of microcrystalline cellulose and Ganoderma fiber

The sustained-release effects of codried excipient of modified Ganoderma (treated with alkaline solution) and microcrystalline cellulose at different ratios were examined using acetaminophen (ACT) as a model drug. Results demonstrate that the crushing strength of most ACT tablets made with codried powder at all ratios increased as compaction force increased; but a rapid decline was observed when compression force exceeded 2 tons. Drug release from tablets compressed at 0.5 ton increased as modified Ganoderma fiber content increased. But when the compression force exceeded 1 ton, the release rate was not influenced by the compaction force or the increasing content of Ganoderma fiber. However, the dissolution of ACT from these tablets could be sustained for longer than 24 h. The extent of drug release was shown to increase with increasing amounts of modified Ganoderma in the codried excipient. The addition of disintegrants could further accelerate the drug release from the tablet. Drug release was also dependent upon the amount and kind of disintegrant used. The influence was in the following order: primojel>crospovidone>starch 1500.

Starch Gelatinization Under Thermal Stress

The behavior under thermal stress of starch dispersed in water was studied by differential scanning calorimetry (DSC) to estimate the heat transported through the aqueous medium in gelatinization, and to characterize the range of gelatinization temperatures. In DSC scanning mode, the endotherm of 10% starch in aqueous dispersion showed the tracing of gelatinization at between 67 and 80°C, having an onset at approximately 69°C. In the isothermal mode, characteristically distinct isothermal heat flow profiles were revealed. It was hypothesized that the thermal influx proposed as being analogous to the diffusion process may affect the profiles. The profiles were transformed and nonlinearly fitted according to the square root of time model to characterize a so-called t-parameter, which was related to mean square displacement of molecular distribution. The t-parameter of starch in excess of water decreased compared to that of water only. The plot of difference in these t-parameters, expressed as Δ, against temperature showed a dramatically decreased Δ at the temperature between 66.7 and 75.2°C, which coincided with the findings from scanning mode DSC. It was further hypothesized that the decreased Δ may be due to the gelatinizing process. According to the theory of polymer solution, the critical temperature (Θ) at 75.2°C, where the free energy became theoretically negative, i.e., the starch became spontaneously dissolved, was drawn. This Θ was located within the range of gelatinizing temperatures. It was deduced that starch polymer may have dissolved during gelatinization. The dissolution from acetaminophen tablets prepared by starch paste was lower compared with that of negative controls (without paste). Moreover, the paste prepared at gelatinizing temperature (70°C) seemed to inhibit acetaminophen dissolution from tablet matrices more than that prepared at subgelatinizing temperature (50°C).

Evaluation of various dissolution media for predicting in vivo performance of class I and II drugs.

In this paper we seek to verify the differences in dissolution behavior between class I and class II drugs and to evaluate the suitability of two new physiologically based media, of Simulated Gastric Fluid (SGF) and of milk for their ability to forecast trends in the in vivo performance of class II compounds and their formulations. Dissolution behavior of two class I drugs, i.e. acetaminophen and metoprolol, and of three class II drugs, i.e. danazol, mefenamic acid and ketoconazole, was studied with USP Apparatus 2 in water, SGF, milk, Simulated Intestinal Fluid without pancreatin (SIFsp) and in two media simulating the small intestinal contents in the fed (FeSSIF) and fasted (FaSSIF) states, respectively. Class I powders dissolved rapidly in all media tested. Acetaminophen dissolution in milk was slow from one tablet formulation, in all other cases dissolution was more than 85% complete in 15 minutes. The dissolution rate of metoprolol was shown to be dependent on formulation and manufacturing method, and one of the three tablet formulations did not meet compendial specifications (80%/30 minutes). Dissolution behavior of class II drugs was greatly affected by choice of medium. Dissolution from a capsule formulation of danazol proved to be dependent on the concentration of solubilizing agents, with a the 30-fold increase in percentage dissolved within 90 minutes upon changing from aqueous media without surfactants to FaSSIF. Use of FeSSIF or milk as the dissolution medium resulted in an even greater increase in percentage dissolved, 100 and 180-fold respectively. Dissolution of the weak acid mefenamic acid from a capsule formulation is dependent on both pH and bile salt concentration, which leads to an offset between increased bile salt concentration and lower pH in the fed state compared to the fasted state medium. The weak base ketoconazole showed complete dissolution from a tablet formulation in Simulated Gastric Fluid without pepsin (SGFsp) within 30 minutes, 70% dissolution in 2 hours under fed state simulated upper jejunal conditions but only 6% dissolution in 2 hours under fasted state conditions. As predicted, dissolution of class II drugs proved to be in general much more dependent on the medium than class I drugs. With the array of compendial and physiological media available, it should be possible to design a suitable set of tests to predict the in vivo dissolution of both class I and II drugs from immediate release formulations.

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.

Automated analytical systems for drug development studies. II — A system for dissolution testing

Microdialysis is a non-equilibrium dynamic sampling method in which the analytes diffuse across a semipermeable membrane due to a concentration gradient and are carried away by the constantly pumping perfusion medium for on-line analysis. A BAS, Inc. microinfusion pump/injector and an on-line LC system were interfaced with a dissolution apparatus to automate dissolution testing of tablets. A DL-5 microdialysis loop probe was suspended in the dissolution medium for sampling. The automated system was used reproducibly (RSD < 2%) to measure the dissolution of acetaminophen and Sulfatrim tablets. Drug recovery from the microdialysis probe was a function of the perfusion rate at constant temperature. However, microdialysis recovery was independent of drug concentration over the linear ranges of the assays for the analytes of interest. Dissolution profiles determined by microdialysis sampling were compared with manual sampling. Identical profiles were obtained for acetaminophen tablets in water at 37 degrees C and 50 rpm by both sampling methods. Dissolution of Sulfatrim tablets was determined in 0.1 M hydrochloride acid at 37 degrees C and 75 rpm. Microdialysis sampling permitted the use of a specially designed perfusion medium to buffer the acidic samples before injecting onto the LC column. Dissolution profiles of sulphamethoxazole were comparable for both sampling methods; however, microdialysis sampling indicated slightly higher release of trimethoprim from the Sulfatrim tablets, which was attributed to release of adsorbed drug from the connecting tubing.

Application of low substituted hydroxypropylcellulose (L-HPC) in the production of pellets using extrusion/spheronization

Low-substituted hydroxypropyl cellulose (L-HPC) was used as a binder and disintegrant in granulation and tabletting. The influences of L-HPC on the extrusion process and the characteristics of pellets prepared by extrusion/spheronization were studied. In one trial the type of L-HPC was varied, in a second the amount of L-HPC LH 20. In both trials pellets were manufactured using different quantities of granulation fluid. Depending on the formulation a working range for water contents leading to beads was defined. In the upper part of the working range the quality of the spheres was good in terms of aspect ratio and sphericity. However, the dissolution rate was found to decrease as the water content of the extrudate increased. All types of L-HPC accelerated the dissolution of acetaminophen. There was no strong correlation between porosity and dissolution time, but increasing porosity tended to lead to faster dissolution. Pellets without L-HPC combined low dissolution rate with low porosity while those with L-HPC LH 20 showed the highest dissolution rate and the greatest porosity.