ABSTRACT
The nanoemulsified composite (NEC) delivery system is a patented technology based on the incorporation of a double microemulsion into microporous carrier. This approach was applied on the very water insoluble ubidecarenone drug. The resulting composite powder showed good technological properties such as flowability; also good stability was evidentiated, with size of the nano-droplets released from the systems maintained equal to the starting size also after a long storage. Furthermore very good biopharmaceutical properties were originated, with water solubility concentrations up to 50-fold higher than pure ubidecarenone and oral absorption in rats up to three-fold greater than standard commercial products in terms of plasma levels and AUC.
Subject(s)
Nanotechnology/methods , Ubiquinone/analogs & derivatives , Absorption , Administration, Oral , Animals , Antioxidants/administration & dosage , Antioxidants/pharmacokinetics , Area Under Curve , Chromatography, High Pressure Liquid/methods , Coenzymes , Drug Carriers/administration & dosage , Drug Carriers/pharmacokinetics , Emulsions , Powders , Rats , Rats, Wistar , Solubility , Time Factors , Ubiquinone/administration & dosage , Ubiquinone/blood , Ubiquinone/pharmacokineticsABSTRACT
This paper deals with the development of proper mathematical models for the calculation of the in vivo rat intestinal drug permeability resorting to two different kinds of experimental methods: the single pass and the recirculating perfusion techniques. In particular, in the single pass case, attention is focused on the effect of water exchange between the flowing solution and the intestinal wall, as this can sensibly affect the permeability determination. In both the single pass and the recirculating perfusion method, a complete radial mixing of the flowing solution is supposed to hold, so that drug concentration and solution velocity are radius independent. Nevertheless, they depend on the intestinal axial position. Accordingly, two distinct models are built up by resorting to microscopic mass balances. The reasonably good data fitting performed by the recirculating perfusion model ensures that the most important factors affecting the passive drug (Antipyrine) diffusion through a rat intestinal wall are properly accounted for. Moreover, the reliability of the developed models and the experimental tests is proved by the fact that the drug (Antipyrine) permeability determined by means of the two methods is statistically equal.
Subject(s)
Intestinal Absorption , Algorithms , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Antipyrine/pharmacokinetics , In Vitro Techniques , Male , Models, Biological , Perfusion , Rats , Rats, Sprague-Dawley , Rats, WistarABSTRACT
A series of substituted 2-benzylidene-3(2H)-benzofuranone-5-carboxylic acids were synthetized and tested for antiallergic activity by the passive cutaneous anaphylactic reaction in the rat. Many compounds display an antiallergic activity comparable to that of disodium chromoglycate when administered parenterally: in addition some derivatives are effective when given by mouth.
