Impact of physical properties of formulations on bioavailability of active substance: current and novel drugs with cyclosporine.
During the long period of cyclosporine-containing dosage forms development a lot of significant findings have been done especially in the field of drug delivery systems. Currently available drugs are based, from technological point of view, on self-dispersible drug delivery systems, which contain cyclosporine solved in pharmaceutically acceptable vehicle. One can find difference among particular systems: (a) at particle size distribution after dispergation; (b) at composition; and (c) at bioavailability of cyclosporine. As far as improvement of bioavailability between original brand leader formulation Sandimmune and recent brand leader formulation Neoral was followed by significant improvement in particle size distribution, it was generally assumed that the reason for this improvement have been found. Several other formulations, e.g. Consupren or SangCyA-self-dispersible systems, more or less correspond with above-mentioned theory that smaller is better and by this principle bridged liquid based dosage forms with solid dosage forms. Bioavailability of novel drug delivery system which gives coarse dispersion with average particle size between 1-150 microm when dispersed have been tested on healthy volunteers. No difference among pharmacokinetic parameters of novel drug delivery system and microemulsion system have been observed in spite of fact that average particle size of novel system is almost 1000x bigger.
Andrysek
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GALENA a.s., Department of Biopharmacy and Pharmacokinetics, Research & Development, Ostravska 29, 747 70 Opava 9, Czech Republic.
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004304:Dosage Forms; D016503:Drug Delivery Systems; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D010316:Particle Size
D004304:Dosage Forms; D007166:Immunosuppressive Agents; D016572:Cyclosporine