In vitro nimesulide absorption from different formulations.

In light of improving the bioavailability of poorly water-soluble drugs, this work focused on the comparison among different nimesulide formulations resorting to in vitro absorption experiments through everted rat intestine. The performance of a nimesulide ethanol-triacetin solution, an activated system made up by cogrinding nimesulide/polyvinylpyrrolidone and simple solid nimesulide were compared with that of a reference nimesulide solution. Although ethanol-triacetin solution showed a better performance than the solid nimesulide because wettability problems connected with nimesulide were completely zeroed, the activated system showed a better performance than the reference solution one. This was due to the fact that the activated system allowed to overcome both the wettability and solubility problems connected with nimesulide. Moreover, as proved by intestinal pictures taken before and after permeation experiments, we observed the adhesion of polymeric particles to intestinal villi, this giving origin to a thin layer, surrounding the intestine, characterized by a nimesulide concentration higher than that in the release environment bulk. A proper mathematical model, based on Fick's second law, was developed to model drug absorption in the case of solution and activated system. In this manner, we could calculate nimesulide permeability through the intestinal wall, and we could better define the nature of the above-mentioned thin layer surrounding the intestine. Finally, the mathematical model was used to verify the theoretical correctness of the widely employed technique consisting in data correction for dilution when sample withdrawal and replacement were needed to measure drug concentration in the receiver environment.

Characterization of a quaternary liquid system improving the bioavailability of poorly water soluble drugs.

The aim of this work is the characterization of the quaternary system composed of water, triacetin (oil), ethanol (alcohol), and Tween 80 (surfactant), as its results enable the enhancement of the bioavailability of nimesulide, a poorly water soluble nonsteroidal antiinflammatory drug widely employed in the pharmaceutical field. Particular attention is devoted to the surfactant-free ternary system, as it proved able to solubilize nimesulide as well, and the absence of a surfactant is desirable in order to keep the preparation as tolerable as possible. Both bulk and interfacial properties of this system are investigated, and a mathematical model to calculate the interface composition of a three-component two-phase system is developed. This model is based on Gibbs' theory on interfaces, which considers an arbitrary mathematical dividing surface so that the two phases continue uniformly up to it, although interface regions have no sharply defined boundaries. We find that both the quaternary and the ternary systems investigated show a miscibility lacuna and that, in the surfactant-free ternary system, an increase of the ethanol weight fraction is reflected as an impoverishment of the ethanol interfacial molar fraction.

Modelling of drug-release from poly-disperse microencapsulated spherical particles.

The topic of this paper is the experimental and theoretical study of drug-release from a system of polydisperse microencapsulated particles that, for the sake of simplicity, are assumed to be spherical. The theoretical analysis performed yields of a mathematical model to describe the physical phenomena involved in drug-release from such a system. In particular, the model is based on the hypothesis of a progressive dissolution of the internal solid drug core (due to solvent penetration through the coating) that gives a liquid solution in the region between the coating and the dissolving solid core. The existence of a concentration gradient between the inner solution and the outer release environment determines drug diffusion through the coating. The coacervation technique was adopted to microencapsulate the solid drug cores (theophylline, a bronchodilator for the treatment of chronic asthma and chronic obstructive lung disease) by an insoluble polymeric layer of ethylcellulose. The amount of drug released from these microencapsulated particles to the external receiver phase is monitored by means of a UV spectrophotometer. As the proposed model fits the experimental results well, it was concluded that it can be a good tool to design and to study this kind of drug-release system.

Methodology of a controlled clinical study for cerebral aging evaluation.

A multicentre study was planned and executed to evaluate the effect of acetyl-L-carnitine in the treatment of cerebral aging. Using 42 health centres, whose comparability of methodology was ensured through a training seminar and an instructional booklet on the psychometric battery of tests employed, some 400 elderly patients aged 60-80 years were enrolled using strict selection criteria. Treatment was run in four phases over 150 days. The first phase, serving as the baseline evaluation, defined through a battery of tests, consisted of 30-day placebo treatment. In the second phase of 45 days, daily treatment with 1500 mg acetyl-L-carnitine was given followed by a psychometric evaluation. For the next 45 days the same drug therapy was employed with a complete psychometric evaluation on the final day. In the last phase of 30 days the placebo was again administered and a final assessment made of the residual benefits of the 90-day treatment with acetyl-L-carnitine. Using this plan made it possible to evaluate the placebo effects, perform cross-study comparisons and demonstrate the effectiveness of the drug treatment.