In vivo evaluation of tablets and capsules containing spray-dried o/w-emulsions for oral delivery of poorly soluble drugs.
It is recognised that poorly soluble drugs may show an increased oral bioavailability when incorporated in o/w-emulsions. Encapsulating the emulsion lipid droplets in hydroxypropyl methylcellulose (HPMC) by spray drying has been demonstrated to preserve an improved bioavailability releasing lipid droplets from the powder in vivo. However, the spray-dried powder is cohesive and bulky requiring additional processing to improve handling. This was resolved in previous work where a directly compressible dry emulsion formulation was described. The purpose of the present study is to investigate the oral bioavailability resulting from administration of a directly compressible dry emulsion as a tablet and compare it with a HPMC dry emulsion powder and a simple lipid solution. Four female Beagle dogs received a single dose of each formulation containing the same amount of medium-chain triglycerides (MCT) and a model drug, Lu 28-179. Cyclodextrin solutions administered orally and intravenously were used as references. The absolute bioavailability decreased in the order cyclodextrin solution (0.14), HPMC dry emulsion (0.11), technically improved dry emulsion (0.10) and MCT solution (0.06). The directly compressible dry emulsion tablets were concluded to be comparable to a HPMC dry emulsion powder in terms of bioavailability. The lack of statistically significant differences relative to a MCT solution was ascribed to a low and variable absolute oral bioavailability of the model drug.
Hansen
Tue
T
Pharmaceutical Development, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. tueh@ludbeck.com
Holm
Per
P
Rohde
Morten
M
Schultz
Kirsten
K
D000284:Administration, Oral; D000818:Animals; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D004285:Dogs; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions / Q000008:administration & dosage* / Q000378:metabolism; D005260:Female; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000097:blood; D012995:Solubility / Q000187:drug effects; D013607:Tablets
D002214:Capsules; D004655:Emulsions; D004364:Pharmaceutical Preparations; D013607:Tablets