Production of Carbopol 974P and Carbopol 971P pellets by extrusion-spheronization: optimization of the processing parameters and water content.

Pellets obtained by extrusion-spheronization represent multiparticulate dosage forms whose interest in intestinal drug delivery can be potentiated and targeted through bioadhesive properties. However, adhesion itself makes the process difficult or even impossible. The problem of tackiness encountered with bioadhesive wet masses was previously eliminated by the use of electrolytes such as CaCl2. This approach is known to reduce the viscosity of polyacrylic acids by disturbing the interactions between carboxylate groups on adjacent polymer molecules, thereby decreasing their bioadhesive properties. The present study aimed at producing pellets containing carbomers without addition of electrolytes in order to maintain their bioadhesive potentiality at its maximum. Carbopol 974P (10%, 15% and 20%) and Carbopol 971P (10%) were used in combination with Avicel PH101. The extrusion speed (30, 45, 60, 90, and 150 rpm), spheronizer speed (350, 700, 960, 1000, and 1300 rpm), spheronization time (5, 10, 15, and 20 minutes) and amount of water (45%, 50%, 54%, and 58%) were optimized in order to obtain the highest yield of spherical pellets ranging 710-1000 microm in diameter. For pellets containing 10%, 15% Carbopol 974P or 10% Carbopol 971P and 45% water content, 30 rpm extrusion speed, 960 rpm, and 10 minutes spheronization speed and time led to the highest yields and sphericities, respectively, 72% and 0.91, 67% and 0.78, and 76% and 0.80. Production of pellets with 20% Carbopol 974P could be achieved through the increase of the water content up to 58% and implementation of 30 rpm extrusion speed, 1300 rpm, and 10 minutes spheronization speed and time. The yield and sphericity were 42% and 0.78 respectively.

Gastrointestinal transit of pellets in rats: effect of size and density.

Gastrointestinal distribution kinetics of a large amount (0.5-1 g) of three types of non-disintegrating pellets which had the same size (S1, 710-1000 micrometers) but different densities (D1, 0.9 and D2, 1.5 g cm-3), or which had the same density (D1) but different diameters (S1 and S2, 1250-1600 micrometers) were examined in fed rats. The percentage of pellets remaining in the stomach, small gut, caecum and colon was measured at suitable intervals. Whatever the size of the pellets, the heavier the density, the longer the gastric emptying (2.1 h for D2-S1 instead of 1.3 h for D1-S1 and 0.7 h for D1-S2). The small gut transit time was not influenced by density but was slightly prolonged by size: 3.3 h for D1-S2 instead of 2.6 h for D1-S1 and D2-S1. Conversely, the gastrocolonic transit time was widely influenced by density (13.5 h for D2-S1) and somewhat by size (8.2 h for D1-S2 and 4.5 h for D1-S1). This delays were proportional to caecal residence time in the large, sacculated and derivated caecum of rats. In order to use the rat as an experimental model for pharmaceutical pellets, those results should have implication for the design of dosage forms, particularly those for controlled or timed release or those for targeted release at specific positions in the gastrointestinal tract.

Aminotransferases in elderly people: influence of pyridoxal 5'-phosphate addition on the determination of serum aminotransferases in healthy elderly subjects.

Aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) activity was measured in a group of 81 healthy subjects over 70 years of age and another of 180 younger persons, in order to investigate histograms and means of aminotransferase values in both groups and the variation in stimulation of these enzyme activities by pyridoxal 5'-phosphate (P5P) added in vitro. It was found that ASAT and ALAT mean values were significantly higher in both groups in the presence of P5P, than in the absence of P5P. ASAT and ALAT mean values obtained with and without P5P in old people were similar to those found in young subjects. In addition, mean stimulation percentages by P5P were identical in both groups.