An investigation into the influence of drug lipophilicity on the in vivo absorption profiles from subcutaneous microspheres and in situ forming depots.
Drug lipophilicity is known to have a major influence on in vivo drug absorption from intramuscularly and subcutaneously administered solutions. Indeed, chemical modification to increase drug lipophilicity is used to enable sustained drug release from solutions. In contrast to the wealth of knowledge on drug release from simple solutions, the influence of drug lipophilicity on its release from controlled release formulations, such as, microparticles and in situ forming depots, have not been systematically studied. Controlled release vehicles are designed to 'control' drug release, hence, in vitro studies show negligible influence of drug lipophilicity on release. The situation could however be different in vivo, due to interactions between the vehicle and biological tissue. We therefore investigated the influence of drug lipophilicity on its in vivo release in rats from two controlled release formulations, PLGA microparticles and in situ forming depots. Both systems exhibited a burst drug release. Subsequent to the burst release, we found that lipophilicity did not influence the rate or extent of drug absorption from the two formulations over a 10-day study period, which would imply that drug partitioning out of the depots was not the main mechanism of drug release from both formulations. This study must however be repeated with a greater number of animals to increase its power.
Deadman
Claire M
CM
Department of Pharmaceutics, School of Pharmacy, University of London, UK.
Kellaway
Ian W
IW
Yasin
Mohammed
M
Dickinson
Paul A
PA
Murdan
Sudaxshina
S
D000327:Adsorption; D000526:Alprenolol / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D000818:Animals; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004343:Drug Implants; D057927:Hydrophobic and Hydrophilic Interactions; D007279:Injections, Subcutaneous; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D008790:Metoprolol / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D008863:Microspheres; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D051381:Rats
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004343:Drug Implants; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000526:Alprenolol; D008790:Metoprolol