Effect of Formulation and Process Variables on the Dissolution Profile of Naproxen Sodium from Tablets

Abstract

Results of this investigation revealed some important formulation characteristics of naproxen sodium. Tablets made from the granules, prepared by wet granulation method using water, showed a significant decrease in solution as compared to those made by dry blending method. During wet granulation, heat was evolved due to the hydration of naproxen sodium resulting in the retardation of dissolution. The pseudo-polymorphism and hydration is being investigated by Bansal et. al. (1). In addition, when polyvinyl pyrolidone (PVP K-90) was used instead of PVP K-30, the dissolution was further retarted. Addition of cross carmellose sodium (Ac-Di-Sol) did not change the dissolution behavior of these tablets. When naproxen sodium was granulated with water, a decrease in dissolution rate was observed as mixing time was increased from 5 minutes to 15 minutes. The increase in hardness of the tablet from 10 Kp to 18Kp did not alter the dissolution profile of naproxen sodium. When granulation was prepared using a low shear mixer (Planetary mixer) versus a high shear mixer (T.K. Fielder), the resultant tablets exhibited similar dissolution and physical chemical properties.     

Tablet-to-Tablet Dissolution Variability and its Relationship to the Homogeneity of a Water Soluble Drug

The homogeneity of a water soluble drug in a tablet granulation was studied by mixing the granulated drug with excipients in a V-shaped tumbling mixer. Samples were withdrawn from five different locations of the mixer for homogeneity and dissolution studies at different mixing times. For dissolution studies, tablets were compressed at a constant compression load. Qualitatively, the coefficient of variation of mixing and dissolution looked similar, suggesting that the mixing homogeneity may have some relationship to the tablet-to-tablet dissolution variability. The addition of magnesium stearate resulted in an increase in the coefficient of variation of mixing and a decrease in the dissolution rate. A large decrease in the dissolution rate occured during the first minute of mixing with the magnesium stearate. The tablet crushing strength continuously decreased during the first 10 minutes of mixing with the magnesium stearate. The results suggested that the formulation in which a major portion of the excipients was not wet granulated with the drug resulted in higher tablet-to-tablet dissolution variability. The addition of sodium starch glycolate or sodium carboxymethyl cellulose to starch for enhancing disintegration neither improved the tablet-to-tablet dissolution variability nor increased the rate of drug dissolution.     

Factors Affecting Rate of Dissolution of Prednisone from Tablets

A study was carried out to evaluate some parameters which may have an effect on the dissolution rate of prednisone from tablets. The parameters examined involving formulation were: diluent proportion (Lactose-starch), dissintegrant type (starch, explotab (sodium starch glycolate) type of binder (starch paste, gelatine water solution and PVP alcoholic solution), lubricant, and dye concentration. The Manufacturing variables studied were: method of manufacture (wet granulation, direct compression and double compression), granule size in wet granulation and tablet hardness. dissolution profiles of tablets storaged 2 months at 45°C were compared with those of fresh samples. Tablets prepared with prednisone five years old, tablets with fresh active ingredient and tablets with two different prednisone concentrations (5 and 50 mg per tablet) were used for other evaluations.

In all cases micronized prednisone was used and all batches were physically and chemically evaluated before studying their dissolution following the USP basket method.

The parameters studied that affected significatively dissolution rate of prednisone were: type of binder, lubricant concentration, method of manufacture, active ingredient, age and prednisone concentration.     

Factors Affecting Rate of Dissolution of Prednisone from Tablets

Abstract

A study was carried out to evaluate some parameters which may have an effect on the dissolution rate of prednisone from tablets. The parameters examined involving formulation were: diluent proportion (Lactose-starch), dissintegrant type (starch, explotab (sodium starch glycolate) type of binder (starch paste, gelatine water solution and PVP alcoholic solution), lubricant, and dye concentration. The Manufacturing variables studied were: method of manufacture (wet granulation, direct compression and double compression), granule size in wet granulation and tablet hardness. dissolution profiles of tablets storaged 2 months at 45°C were compared with those of fresh samples. Tablets prepared with prednisone five years old, tablets with fresh active ingredient and tablets with two different prednisone concentrations (5 and 50 mg per tablet) were used for other evaluations.

In all cases micronized prednisone was used and all batches were physically and chemically evaluated before studying their dissolution following the USP basket method.

The parameters studied that affected significatively dissolution rate of prednisone were: type of binder, lubricant concentration, method of manufacture, active ingredient, age and prednisone concentration.     

Extrusion granulation and high shear granulation of different grades of lactose and highly dosed drugs: a comparative study

Formulations containing different lactose grades, paracetamol, and cimetidine were granulated by extrusion granulation and high shear granulation. Granules were evaluated for yield, friability, and compressibility. Tablets were prepared from those granules and evaluated for tensile strength, friability, disintegration time, and dissolution. The different lactose grades had an important effect on the extrusion granulation process. Particle size and morphology affected powder feeding and power consumption, but had only a minor influence on the granule and tablet properties obtained by extrusion granulation. In contrast, the lactose grades had a major influence on the granule properties obtained by high shear granulation. Addition of polyvinylpyrrolidone (PVP) was required to process pure paracetamol and cimetidine by high shear granulation, whereas it was feasible to granulate these drugs without PVP by extrusion granulation. Granules prepared by extrusion granulation exhibited a higher yield and a lower friability than those produced by high shear granulation. Paracetamol and cimetidine tablets compressed from granules prepared by extrusion granulation showed a higher tensile strength, lower friability, and lower disintegration time than those prepared from granules produced by high shear granulation. Paracetamol tablets obtained via extrusion granulation exhibited faster dissolution than those obtained via high shear granulation. For all lactose grades studied, extrusion granulation resulted in superior granule and tablet properties in comparison with those obtained by high shear granulation. These results indicate that extrusion granulation is more efficient than high shear granulation.     

Physical Properties and Stability of Diazepam and Phenobarbitone Sodium Tablets Prepared with Compactrol

Abstract

Compactrol as a newly introduced direct compressible vehicle was used for the preparation of Diazepam and phenobarbitone sodium tablets. Spray dried lactose and wet granulation technique were also employed to prepare these tablets for comparison. The effect of storage at 75% RH, at two temperature levels (25° and 45°) on the physical properties of these tablets was studied for 6 weeks. It was found that, there were an increase in tablet weight, thickness and friability per cent, while a significant decrease in hardness was observed. Tablets prepared with compactrol showed no significant changes in both disintegration and dissolution times, while tablets prepared with spray dried lactose showed a marked decrease in disintegration and dissolution times. On the other hand, tablets prepared by wet granulation showed a pronounced in crease in both disintegration and dissolution times.     

Disintegration and Dissolution Parameters of Compressed Tablets Prepared by Direct Compression-Wet Granulation Process and Compression of Wet Granulation of Both Sections

Hardness, disintegration and dissolution of compressed tablets were assessed by compressing tablets from granulations prepared by dry and wet granulation process of two sections and by composite wet granulation process. Modified USP XVIII apparatus for disintegration, rotating basket apparatus USP XVIII and constant circulation apparatus were employed for measuring dissolution. The constant circulation apparatus was used in the studies as only it proved to be sensitive to reflect the differences in the dissolution rates and was a close analog of physiological situation. Four types of tablets containing acetylsalicylic acid, codeine phosphate and propoxyphene hydrochloride were prepared. Tablets prepared by partial dry and wet granulation process did not show significant differences in the rates of dissolution as compared to those prepared by complete wet granulation process.     

Dextrose monohydrate as a non-animal sourced alternative diluent in high shear wet granulation tablet formulations

The feasibility of dextrose monohydrate as a non-animal sourced diluent in high shear wet granulation (HSWG) tablet formulations was determined. Impacts of granulation solution amount and addition time, wet massing time, impeller speed, powder and solution binder, and dry milling speed and screen opening size on granule size, friability and density, and tablet solid fraction (SF) and tensile strength (TS) were evaluated. The stability of theophylline tablets TS, disintegration time (DT) and in vitro dissolution were also studied. Following post-granulation drying at 60?°C, dextrose monohydrate lost 9% water and converted into the anhydrate form. Higher granulation solution amounts and faster addition, faster impeller speeds, and solution binder produced larger, denser and stronger (less friable) granules. All granules were compressed into tablets with acceptable TS. Contrary to what is normally observed, denser and larger granules (at ≥21% water level) produced tablets with a higher TS. The TS of the weakest tablets increased the most after storage at both 25?°C/60% RH and 40?°C/75% RH. Tablet DT was higher for stronger granules and after storage. Tablet dissolution profiles for 21% or less water were comparable and did not change on stability. However, the dissolution profile for tablets prepared with 24% water was slower initially and continued to decrease on stability. The results indicate a granulation water amount of not more than 21% is required to achieve acceptable tablet properties. This study clearly demonstrated the utility of dextrose monohydrate as a non-animal sourced diluent in a HSWG tablet formulation.     

Disintegration and Dissolution Parameters of Compressed Tablets Prepared by Direct Compression-Wet Granulation Process and Compression of Wet Granulation of Both Sections

Abstract

Hardness, disintegration and dissolution of compressed tablets were assessed by compressing tablets from granulations prepared by dry and wet granulation process of two sections and by composite wet granulation process. Modified USP XVIII apparatus for disintegration, rotating basket apparatus USP XVIII and constant circulation apparatus were employed for measuring dissolution. The constant circulation apparatus was used in the studies as only it proved to be sensitive to reflect the differences in the dissolution rates and was a close analog of physiological situation. Four types of tablets containing acetylsalicylic acid, codeine phosphate and propoxyphene hydrochloride were prepared. Tablets prepared by partial dry and wet granulation process did not show significant differences in the rates of dissolution as compared to those prepared by complete wet granulation process.     

The Effect of the Wet Granulation Process on Drug Dissolution

Abstract

Wet granulation can be an important processing step for pharmaceutical solid dosage forms. In this investigation emphasis was directed towards the influence of a “simple” wet granulation process on drug release from granules and their resulting tablets. Direct compression blends of the same materials were used as controls. Binary mixtures containing a 5% level of either theophylline, hydrochlorothiazide or chlorpheniramine maleate in microcrystalline cellulose or lactose were granulated with water. Experimentally, the powders were dry blended in a planetary mixer, wet granulated, and subsequently wet milled and dried. No dry milling step was included. Granule characterization consisted of particle size, density, porosity, compression and dissolution testing. Dissolution results varied with the drug, as expected, and dissolution at 10 minutes ranged from 35 to 95 % release. In general, however, the results indicate that dissolution from granules and the corresponding direct compression blend are similar. Although differences in compressibility were observed in the systems studied, granulation was not found to be detrimental to drug release.     

Chitosan and Sodium Sulfate as Excipients in the Preparation of Prolonged Release Theophylline Tablets

The major objectives of this study were to monitor the effect of cross-linking of cationic chitosan in acidic media with sulfate anion during granules preparation by wet granulation method prior to tableting using theophylline (TPH) as a model drug. The prepared granules and the compressed tablets were subjected to in vitro evaluation. The properties of the prepared matrix granules and the compressed tablets were dependent on chitosan:sodium sulfate weight ratios, chitosan content, and molecular weight of chitosan. The prepared granules of all batches showed excellent to passable flowability and were suitable for compression into tablets. Most of the granules were hard and expected to withstand handling during the subsequent compression into tablets. Granules with high friabilities were only those prepared with a high amount of sodium sulfate or low amount of chitosan. Compression of granule batches yield nondisintegrating tablets that showed a decrease in tensile strength with the increase of sodium sulfate content at high chitosan:sodium sulfate weight ratio or with decrease of chitosan content. On the other hand, friability of tablets was increased in the presence of an excessive amount of sodium sulfate and low chitosan content as observed with granules. Slow TPH release from the formulated tablets was achieved at 1:0.5 and 1:1 chitosan:sodium sulfate weight ratios where all or most of the cationic chitosan and sulfate anions were used in a cross-linking reaction during wet granulation. Ratios of 1:2 and 1:3 showed fast drug release, which support the hypothesis that excessive unreacted water-soluble sodium sulfate might increase the porosity of the nondesintegrating tablets during dissolution. Slow drug release was also obtained with high molecular weight chitosan, whereas changing the hardness of the tablets did not significantly change the release profile of the drug as long as the tablets are intact during dissolution. Furthermore, slow drug release was observed as the total amount of chitosan was increased in the formulated tablets. A comparative in vivo study between the chosen formulated tablets (1:1 chitosan:sodium sulfate ratio that contains 10% high molecular weight chitosan) and the commercial Quibron® tablets indicated prolonged appearance of the drug in dogs' plasma for both formulations with no significant differences (p > 0.05) in rate and extent of drug absorption. The formulated tablets showed 103.16% bioavailability relative to that of the commercial tablets.     

Chitosan and sodium sulfate as excipients in the preparation of prolonged release theophylline tablets

The major objectives of this study were to monitor the effect of cross-linking of cationic chitosan in acidic media with sulfate anion during granules preparation by wet granulation method prior to tableting using theophylline (TPH) as a model drug. The prepared granules and the compressed tablets were subjected to in vitro evaluation. The properties of the prepared matrix granules and the compressed tablets were dependent on chitosan:sodium sulfate weight ratios, chitosan content, and molecular weight of chitosan. The prepared granules of all batches showed excellent to passable flowability and were suitable for compression into tablets. Most of the granules were hard and expected to withstand handling during the subsequent compression into tablets. Granules with high friabilities were only those prepared with a high amount of sodium sulfate or low amount of chitosan. Compression of granule batches yield nondisintegrating tablets that showed a decrease in tensile strength with the increase of sodium sulfate content at high chitosan:sodium sulfate weight ratio or with decrease of chitosan content. On the other hand, friability of tablets was increased in the presence of an excessive amount of sodium sulfate and low chitosan content as observed with granules. Slow TPH release from the formulated tablets was achieved at 1:0.5 and 1:1 chitosan:sodium sulfate weight ratios where all or most of the cationic chitosan and sulfate anions were used in a cross-linking reaction during wet granulation. Ratios of 1:2 and 1:3 showed fast drug release, which support the hypothesis that excessive unreacted water-soluble sodium sulfate might increase the porosity of the nondesintegrating tablets during dissolution. Slow drug release was also obtained with high molecular weight chitosan, whereas changing the hardness of the tablets did not significantly change the release profile of the drug as long as the tablets are intact during dissolution. Furthermore, slow drug release was observed as the total amount of chitosan was increased in the formulated tablets. A comparative in vivo study between the chosen formulated tablets (1:1 chitosan:sodium sulfate ratio that contains 10% high molecular weight chitosan) and the commercial Quibron tablets indicated prolonged appearance of the drug in dogs' plasma for both formulations with no significant differences (p > 0.05) in rate and extent of drug absorption. The formulated tablets showed 103.16% bioavailability relative to that of the commercial tablets.     

Evaluation of the impact of sodium lauryl sulfate source variability on solid oral dosage form development

Objective: The objective of this study was to investigate the effects of sodium lauryl sulfate (SLS) from different sources on solubilization/wetting, granulation process, and tablet dissolution of BILR 355 and the potential causes. Methods: The particle size distribution, morphology, and thermal behaviors of two pharmaceutical grades of SLS from Spectrum and Cognis were characterized. The surface tension and drug solubility in SLS solutions were measured. The BILR 355 tablets were prepared by a wet granulation process and the dissolution was evaluated. Results: The critical micelle concentration was lower for Spectrum SLS, which resulted in a higher BILR 355 solubility. During wet granulation, less water was required to reach the same end point using Spectrum than Cognis SLS. In general, BILR 355 tablets prepared with Spectrum SLS showed a higher dissolution than the tablets containing Cognis SLS. Micronization of SLS achieved the same improved tablet dissolution as micronized active pharmaceutical ingredient. Conclusions: The observed differences in wetting and solubilization were likely due to the different impurity levels in SLS from two sources. This study demonstrated that SLS from different sources could have significant impact on wet granulation process and dissolution. Therefore, it is critical to evaluate SLS properties from different suppliers, and then identify optimal formulation and process parameters to ensure robustness of drug product manufacture process and performance.     

Mechanisms of Drug Release from Matrices Prepared with Aqueous Dispersion of Ethylcellulose

The objective of this study was to investigate the mechanism of acetaminophen (APAP) release from tablets prepared by the wet granulation method using an aqueous polymeric dispersion (Surelease) as a granulating agent. Tablets compressed from granules containing 10% w/w acetaminophen and 13.44% w/w total solids from Surelease released only 52.4% w/w drug after 120 min of dissolution testing, while controlled tablets without Surelease released 94.1% w/w drug. In order to prepare control tablets of 6.8 Kp hardness value, the upper compressional force recorded was 15.87 kN while tablets containing 13.44% w/w of total solids from Surelease had a recorded force of 6.28 kN. The drug release from tablets prepared with Surelease as a granulating liquid followed the diffusion-controlled model for an inert porous matrix     

Application of near-infrared spectroscopy to optimize dissolution profiles of tablets according to the granulation mechanism

We developed a method for the optimization of dissolution properties of solid oral dosage forms manufacturing using high shear wet granulation (HSWG) by using near-infrared spectroscopy (NIRS) with chemometrics in small-scale experiments. The changes in rheology and NIR spectra of the granules were monitored to verify the granulation mechanism and determine the suitable water amount for model formulation during the HSWG. Tablets were manufactured by altering the added water amount to investigate the impact of the granulation mechanism on drug product qualities. Model formulation granules were prepared with 10–20% w/w water in a funicular state, corresponding to the plateau region in score plots obtained by principal component analysis (PCA). The dissolution rate of model formulation tablets manufactured with more than 20% w/w of water was significantly delayed while tablets manufactured with 15% w/w water showed 100% dissolution at 15?min. NIRS and PCA are applicable to the optimization of dissolution properties via the process understanding of HSWG at the early formulation development stage and could facilitate drug development.     

Effects of manufacturing process variables on in vitro dissolution characteristics of extended-release tablets formulated with hydroxypropyl methylcellulose

The purpose of this study was to investigate the effect of three process variables: distribution of hydroxypropyl methylcellulose (HPMC) within the tablet matrix, amount of water for granulation, and tablet hardness on drug release from the hydrophilic matrix tablets. Tablets were made both by direct compression as well as wet granulation method. Three formulations were made by wet granulation, all three having the exact same composition but differing in intragranular:intergranular HPMC distribution in the matrix. Further, each formulation was made using two different amounts of water for granulation. All tablets were then compressed at two hardness levels. Dissolution studies were performed on all tablets using USP dissolution apparatus I (basket). The dissolution parameters obtained were statistically analyzed using a multilevel factorial-design approach to study the influence of the various process variables on drug release from the tablets. Results indicated that a change in the manufacturing process could yield significantly dissimilar dissolution profiles for the same formulation, especially at low-hardness level. Overgranulation could lead to tablets showing hardness-dependent drug-release characteristics. Studies showed that intergranular addition of a partial amount of HPMC (i.e., HPMC addition outside of granules) provided a significant advantage in making the formulation more robust over intragranular addition (i.e., that in which the entire amount of HPMC was added to the granules). Dissolution profiles obtained for these tablets were relatively less dependent on tablet hardness irrespective of the amount of water added during granulation.     

Comparison of Moisture-Activated Dry Granulation Profess with Conventional Granulation Methods for Sematilide Hydrochloride Tablets

During the development of a tablet formulation of a cohesive, fluffy investigational drug, a novel moisture-activated dry granulation (MADG) process was studied in comparison with two conventional granulation methods, i.e., wet granulation and dry granulation with a roller compactor, as well as with a direct compression formulation method. The MADG method produced granules with excellent flowability which were equivalent in a number of ways to those produced by either conventional wet granulation or dry granulation methods and which were much better than the powder blend from the direct compression formulation. The tablets prepared using the MADG method had better content uniformity than those made using material from wet and dry granulation processes. Other tablet properties, such as weight variation, friability and dissolution, were similar among the tablets produced by the four processes     

The Effect of Mixing Variables on the Dissolution Properties of Direct Compression Formulations of Furosemide

The particles of a number of poorly water soluble drugs, for instance furosemide, tend to agglonierate spontaneously and as a result decrease the drug's dissolution properties. This phenomena is undesirable when the drug is to be formulated in a direct compressible formulation. Interactive or ordered mixing with a filler usually rectifies this problem but the drug load is limited to a maxirnuni of ± 5% of the mixture. This is well below the formulation requirements of hrosemide (25 %) and below the maximum drug load which can be handled in dircct compression formulations (± 35 %). The effect of two types of mixers, the mixing time and drug load were investigated for a direct compression formulation of furosemide tablets. A Turbula and a V mixer, both with a volume of 720 ml, were used. The drug was formulated with Ludipress (a commercial direct compression filler, BASF, Germany) at two drug loadings of 20 and 25 %. Magnesium stearate (1 %) was added as a lubricant. A mixture was prepared for each experimental condition. After mixing the whole mixture (120 gram) was tabletted on a Korsch single punch machine producing ± 500 tablets. The crushing strength, mass and disintegration time of ten tablets and the dissolution of six tablets were measured. Dissolutions were donc according to the USP XXII - method 2¹ - in 0, 1 M HCI and a phosphate buffer with pH = 5.8. The intrinsic dissolution rates of some of the mixtures were also deterniined in the two dissolution media. The dissolution properties of the formulations were compared with the properties of Lasix®, a commercially available furoseniide product. which is not manufactured by dircct compression. The dissolution rates of the formulations mixed in the Turbula mixer were significantly higher than those mixed in the V miser. The area under the dissolution curves increased as a function of niixing time for both mixers. The best dissolution results were obtained for formulations with a 20 % drug load and mixed for 120 minutes in the Turbula miser. The dissolution curves for these formulations compared well with the curves for the commercial tablets. Intrinsic dissolution rates were also a hnction of niising time, which indicates that the increase in dissolution properties is probably a result of the deagglomeration of the agglomerated furosemide particles. The Turbula mixer, which can develop more shear force, breaks the agglomerates quicker and to a larger extend than the V mixer. It can be concluded that the type of mixer, mixing time and drug load control the dissolution properties of direct compression formulations of poorly water soluble drugs in which the drug particles form agglomerates.     

Moisture, Hardness, Disintegration and Dissolution Interrelationships in Compressed Tablets Prepared by the Wet Granulation Process

Interrelationships among moisture, hardness, disintegration and dissolution in compressed tablets were studied by compressing tablets from granulations prepared by the wet granulation process containing low moisture levels. Hardness, disintegration and dissolution of these tablets did not change on exposure to ambient room conditions. After equilibration under high humidities, a decrease in tablet hardness occurred which depended linearly on tablet hardnesses at the time of compression. After overnight exposure to ambient room conditions, the softened tablets increased in hardness and this increase greatly exceeded the initial hardnesses. The magnitude of hardness increase was independent of the hardnesses at the time of compression. Increased tablet hardnesses resulted in an increase in the disintegration time, although in vitro dissolution of the drug remained unaffected. The results suggest that moisture gain and subsequent loss on storage under varying humidity conditions could account for major increases in hardness of compressed tablets in storage.     

The Effect of Mixing Variables on the Dissolution Properties of Direct Compression Formulations of Furosemide

Abstract

The particles of a number of poorly water soluble drugs, for instance furosemide, tend to agglonierate spontaneously and as a result decrease the drug's dissolution properties. This phenomena is undesirable when the drug is to be formulated in a direct compressible formulation. Interactive or ordered mixing with a filler usually rectifies this problem but the drug load is limited to a maxirnuni of ± 5% of the mixture. This is well below the formulation requirements of hrosemide (25 %) and below the maximum drug load which can be handled in dircct compression formulations (± 35 %). The effect of two types of mixers, the mixing time and drug load were investigated for a direct compression formulation of furosemide tablets. A Turbula and a V mixer, both with a volume of 720 ml, were used. The drug was formulated with Ludipress (a commercial direct compression filler, BASF, Germany) at two drug loadings of 20 and 25 %. Magnesium stearate (1 %) was added as a lubricant. A mixture was prepared for each experimental condition. After mixing the whole mixture (120 gram) was tabletted on a Korsch single punch machine producing ± 500 tablets. The crushing strength, mass and disintegration time of ten tablets and the dissolution of six tablets were measured. Dissolutions were donc according to the USP XXII - method 2¹ - in 0, 1 M HCI and a phosphate buffer with pH = 5.8. The intrinsic dissolution rates of some of the mixtures were also deterniined in the two dissolution media. The dissolution properties of the formulations were compared with the properties of Lasix®, a commercially available furoseniide product. which is not manufactured by dircct compression. The dissolution rates of the formulations mixed in the Turbula mixer were significantly higher than those mixed in the V miser. The area under the dissolution curves increased as a function of niixing time for both mixers. The best dissolution results were obtained for formulations with a 20 % drug load and mixed for 120 minutes in the Turbula miser. The dissolution curves for these formulations compared well with the curves for the commercial tablets. Intrinsic dissolution rates were also a hnction of niising time, which indicates that the increase in dissolution properties is probably a result of the deagglomeration of the agglomerated furosemide particles. The Turbula mixer, which can develop more shear force, breaks the agglomerates quicker and to a larger extend than the V mixer. It can be concluded that the type of mixer, mixing time and drug load control the dissolution properties of direct compression formulations of poorly water soluble drugs in which the drug particles form agglomerates.