Evaluation of the disintegration properties of commercial famotidine 20 mg orally disintegrating tablets using a simple new test and human sensory test.

The purpose of this study was to demonstrate the usefulness and broad-applicability of a simple disintegration test method for orally disintegrating tablets (ODT). Eight types of commercial famotidine 20 mg orally disintegrating tablets with different physical properties (formulation, manufacturing method, tablet weight, shape, diameter, thickness, etc.), were used. Disintegration times of these tablets were evaluated employing human sensory test, conventional disintegration test, and the new proposed disintegration test. The human sensory test was performed in 5 healthy volunteers. In the conventional disintegration test, the disintegration apparatus described in the Japanese Pharmacopeia (JP 1(st)) was used. Our proposed new test which is characterized by a rotating shaft with a low weight (10, 15 g) and rotation speed (10, 25, 50 rpm) was evaluated using tablets with and without storage under severe conditions (60 degrees C/75%RH for 1 week). The disintegration times of famotidine 20 mg orally disintegrating tablets in human sensory test varied from 9 to 32 s. In contrast, disintegration times in the conventional test were prolonged to over 300 s. Disintegration times in the new proposed test were close to those in human sensory test. Especially, when the new test was conducted with 15 or 10 g weight and 25 rpm, the slope (human sensory test vs. new proposed test) was almost 1. We were able to demonstrate that the new proposed test was useful to estimate the actual human disintegration time.

Tabletting of solid dispersion particles consisting of indomethacin and porous silica particles.

We attempted to make the rapidly dissolving tablet (Tab) containing solid dispersion particles (SD) with indomethacin (IMC) and porous silica (Sylysia350) as carrier prepared by using spray-drying technique. Rapidly dissolving tablet was formulated with mannitol as a diluent and low substituted hydroxypropylcellulose (L-HPC) or partly pre-gelatinized starch (PCS) as a disintegrant. The percent dissolved from Tab (SD) was higher than that of tablet containing physical mixture (PM) at 20 min. Nearly 100% of drug in Tab (SD) was dissolved within 60 min, while the drug dissolution of Tab (PM) was not completed at the same time period. In addition, the tensile strength of Tab (SD) was much higher than that of Tab (PM). Adding L-HPC in Tab (SD) (Tab (SD-L-HPC)), the percent dissolved from Tab (SD-L-HPC) at 5 min became much higher than that from Tab (SD). The dissolution profile of IMC from Tab (SD-L-HPC) was almost the same irrespective of the compression pressure, while the tensile strength of tablet increased with increasing the compression pressure. In comparing the compaction property of these tablets by observing the ratio of residual die wall pressure (RDP) to maximum die wall pressure (MDP) (RDP/MDP), it was found that addition of L-HPC in the tablet formulation improved compactibility. In case that PCS was formulated as disintegrant, Tab (SD-PCS), similar improvement in the dissolution profile and tensile strength was observed, though the dissolution rate of IMC from Tab (SD-PCS) was slightly lower than that from Tab (SD-L-HPC) irrespective of the compression pressure.

Solid dispersion particles of amorphous indomethacin with fine porous silica particles by using spray-drying method.

The solid dispersion particles of indomethacin (IMC) were prepared with different types of silica, non-porous (Aerosil 200) or porous silica (Sylysia 350) by using spray-drying method. Powder X-ray diffraction analysis showed that IMC in solid dispersion particles is in amorphous state irrespective of the type of silica formulated. In DSC analysis, the melting peak of IMC in solid dispersion particles with Sylysia 350 shifted to lower temperature than that in solid dispersion particles with Aerosil 200 although the peak of each solid dispersion particles was much smaller than that of original IMC crystals. Dissolution property of IMC was remarkably improved by formulating the silica particles to the solid dispersion particles. In comparing the effect of the type of the silica particles, the dissolution rate of solid dispersion particles with Sylysia 350 was faster than that with Aerosil 200. The formulation amount of IMC did not affect on the amorphous state of IMC in the resultant solid dispersion particles in powder X-ray diffraction patterns. However, the area of the melting peak of IMC in the solid dispersion particles increased and an exothermic peak owing to recrystallization was observed with increasing the IMC content in the DSC patterns. The dissolution rate of IMC from the solid dispersion particles with Sylysia 350 was faster than that of Aerosil 200 irrespective of IMC content. In stability test, amorphous IMC in the solid dispersion particles with each silica particles did not crystallize under storing at severe storage conditions (40 degrees C, 75% RH) for 2 months, while amorphous IMC without silica easily crystallized under same conditions.

Die wall pressure measurement for evaluation of compaction property of pharmaceutical materials.

The aim of this study was to evaluate the compaction property of several pharmaceutical materials by measuring the die wall pressure. The profile of die wall force during tabletting process was measured with the compaction process analyzer (TabAll). Several compaction parameters such as maximum die wall pressure (MDP), residual die wall pressure (RDP) and pressure transmission ratio (PTR) from upper punch to lower punch were calculated. The ejection pressure (EP) of tablet compacted was also measured as a parameter for sticking property of the compacts. The profile of die wall force observed was classified to the typical two types, a small type and a large one. Partly pre-gelatinized starch (PCS), cornstarch and low substituted hydroxypropylcellulose (L-HPC) were the small type, while crystalline lactose, ascorbic acid and potassium chloride were the large type. The die wall force of crystalline lactose remarkably increased at the ejection of tablet and then capping was observed. RDP value of PCS, cornstarch, L-HPC was smaller than that of crystalline lactose, ascorbic acid, potassium chloride. As the higher pressure transmission ratio from upper punch to lower punch means a good compressing property of the powder, we proposed that RDP/MDP is a useful parameter for evaluating the compaction property of powders. Although potassium chloride which is strongly plastic deformable powder showed the highest RDP value among the powders tested, the RDP/MDP value was lower than that of crystalline lactose or ascorbic acid and the tensile strength of resultant tablet of potassium chloride was much higher than these powders.