Bioavailability of seocalcitol I: Relating solubility in biorelevant media with oral bioavailability in rats--effect of medium and long chain triglycerides.
Simulated intestinal media (SIM) containing bile salt (BS) and phospholipids (PL) with and without medium chain lipolytic products (MC-LP) or long chain lipolytic products (LC-LP) were developed to study the solubility of seocalcitol. Both MC-LP and LC-LP were studied in order to investigate the influence of fatty acid chain length on the in vitro solubility of seocalcitol. The same solubility of seocalcitol was found in media containing either MC-LP or LC-LP. The bioavailability after oral administration of seocalcitol dissolved in medium chain triglyceride (MCT), long chain triglyceride (LCT), and a reference formulation containing propylene glycol (PG) was studied in vivo in rats. The lipid formulations showed a twofold increase in bioavailability compared with the reference formulation, indicating positive effects of lipids on the bioavailability reflecting a better solubility in the intestine and protection against precipitation of seocalcitol in the gastro intestinal tract. There was no difference in the in vivo bioavailability of seocalcitol between the MCT and the LCT solutions, which correlates with the identical in vitro solubility of seocalcitol in SIM containing MC-LP or LC-LP.
Pharmaceutical Formulation, LEO Pharma A/S, Industriparken 55, DK-2750 Ballerup, Denmark.
Mette
M
Grove
Gitte P
GP
Pedersen
Jeanet L
JL
Nielsen
Anette
A
Müllertz
D000284:Administration, Oral; D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry; D001682:Biological Availability; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D005079:Excipients / Q000737:chemistry; D007408:Intestinal Absorption; D008297:Male; D010743:Phospholipids / Q000737:chemistry; D019946:Propylene Glycol / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012715:Sesame Oil / Q000737:chemistry; D012995:Solubility; D013997:Time Factors; D014280:Triglycerides / Q000494:pharmacology*; D014316:Tritium
D001647:Bile Acids and Salts; D005079:Excipients; D010743:Phospholipids; D014280:Triglycerides; D014316:Tritium; D019946:Propylene Glycol; D012715:Sesame Oil; D002117:Calcitriol; C078903:seocalcitol