Compressibility of gastroretentive pellets coated with Eudragit NE using a single-stroke and a rotary tablet press.

In this study, 15 kinds of powders with different compression mechanisms were used in the process of filling-binding substances in tablets with pellets. Applied substances possessed dominant brittle time-independent mechanism or time-dependent viscoplastic, viscoelastic mechanism of compression. Using 6 kN compression force in a single-stroke tablet press during 150 ms of compression, damage to the polymer film and pellet core was found in all formulations. As a result, the authors observed an increase of releasing rate of verapamil hydrochloride (VH). A larger contact area between powders and pellets and connected with this better protective properties were ensured by powders with time-independent compression mechanism (eg, D-sorbitol or D-mannitol). Unsymmetrically applied compression force was a reason for inconsistent densification and insufficient protection of the pellets. Taking into consideration the low rotation speed of the turret (10 rpm) in the rotary tablet press, the total compaction time was much longer than in the single-stroke tablet press. The compression time in the case of the rotary tablet press should be considered as the sum of the precompression (about 130 ms) and main compression (about 280 ms) phase times. Compression force applied by upper and lower punch in the precompression and main compression phase was affected uniformly on the pellets' surface, and when protected against fragmentation, allowed only some slight deformation. The powders in tablet formulation were fragmentized and rearranged independent of their compression mechanisms. It was found that the releasing rate of VH from pellets compressed by rotary tablet press with 6, 12, and 18 kN of compression force was similar to the releasing rate from uncompressed pellets.

Influence of the type of cellulose on properties of multi-unit target releasing in stomach dosage form with verapamil hydrochloride.

Microcrystalline cellulose (MCC) and powdered cellulose (PC) are commonly used excipients for solid dosage forms e.g., pellets. The aim of this study was to compare the utility of the MCC and PC in the floating pellet cores comprising verapamil hydrochloride (VH) manufactured by extrusion and spheronization and influence on their physical properties like swelling, compressibility and VH release. It was found by scanning electron microscopy (SEM) investigation that porosity of surface of the pellets' cores increased with an increase of PC amount in composition. Differential scanning calorimetry (DSC) analysis indicated the lack of physicochemical interaction between PC and MCC either with VH or with any excipients in the pellet core. Formulation having the highest PC participation were characterized by the highest friability and compressibility and addition of MCC corresponded with a decrease of friability and compressibility. The results on pellets friability were not reflected by the results on the hardness test. It means that the PC contents growth contributes to the hardness growth. The swelling forces of physical mixture of powders containing PC and MCC was different and increased with increasing amount of PC in pellet's core. Pellets' cores were coated with Eudragit NE dispersion. It was found that VH release rate from coated pellets with higher amount of PC was considerably slower in comparison to the pellets containing highest MCC participation.

Myocardial necrosis due to vitamin D3 overdose -- scanning electron microscopic observations.

Our studies were carried out on the hearts of virgin female Wistar rats treated with 100,000 i.u. of vitamin D3 (calciol) per os for 3 consecutive days. Multifocal cardionecrosis was established macroscopically in 70% of the vitamin D-treated rats on the 7th day of the experiment when the rats were in the acute phase of intoxication. Using a scanning electron microscopy (SEM), we received three-dimensional information about the structural changes to the rat myocardium damaged by high doses of vitamin D3. The images of necrotic hearts revealed significant disruption of the structural integrity of the myocardium linked to fragmentation of the cardiac muscle bundles and a visible disruption of the extracellular matrix (ECM) components. In healthy hearts, the structural integrity of the myocardium and the dense network of the extracellular matrix were well preserved. In parallel, the effect of an increasing concentration of free Ca2+ on the total proteolytic activity of the heart muscle homogenate of the healthy and necrotic rats was investigated at neutral pH. These data showed that following vitamin D3 intoxication, the proteolytic processes in the rat hearts occurred in Ca2+ overload or saturation. On the basis of our morphological and biochemical results we can suggest that calcium-activated neutral proteinases may have contributed to the structural alteration of the extracellular matrix components and were in this way involved in vitamin D-induced cardionecrosis.