In vitro simulation of food effect on dissolution of deramciclane film-coated tablets and correlation with in vivo data in healthy volunteers.
The in vitro dissolution profiles of deramciclane 30 mg film-coated tablets, an acid-labile new 5-HT receptor antagonist, were studied under simulated fasting and fed conditions. Artificial gastric juice with pH adjusted to that of fasting conditions was applied either alone or after adding different dietary components. The use of the USP dissolution apparatus II (paddle method) showed that the presence of dietary components has markedly affected the amount of unchanged drug dissolved. As a similar tendency had been observed in food-effect studies in healthy volunteers, cumulative area under the curve (AUC(cum)) for both fed and fasting conditions were compared and an in vitro--in vivo correlation (IVIVC) was evaluated. A linear relationship was established between logarithmic in vivo blood sampling time and in vitro dissolution time assigned to equal AUC(cum) ratios (AUC(cum, fed)/AUC(cum, fasting)). Despite its limitations, in vitro modelling of in vivo conditions might help provide a base for predicting in vivo drug behaviour.
Al-Behaisi
Samar
S
Research & Development Directorate, EGIS Pharmaceuticals Ltd., Keresztúri út 30-38, H-1106 Budapest, Hungary. abehaisi@axelero.hu
Antal
István
I
Morovján
György
G
Szúnyog
József
J
Drabant
Sándor
S
Marton
Sylvia
S
Klebovich
Imre
I
D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D001892:Camphanes / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000494:pharmacology; D005215:Fasting / Q000502:physiology; D018565:Food-Drug Interactions; D005750:Gastric Juice / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D012995:Solubility; D013608:Tablets, Enteric-Coated
D014151:Anti-Anxiety Agents; D001892:Camphanes; D004041:Dietary Fats; D013608:Tablets, Enteric-Coated; C060555:deramciclane