Bioavailability of seocalcitol I: Relating solubility in biorelevant media with oral bioavailability in rats--effect of medium and long chain triglycerides

TY - JOUR

T1 - Bioavailability of seocalcitol I: Relating solubility in biorelevant media with oral bioavailability in rats--effect of medium and long chain triglycerides

AU - Grove, Mette

AU - Pedersen, Gitte P

AU - Nielsen, Jeanet L

AU - Müllertz, Anette

N1 - Keywords: Administration, Oral; Animals; Bile Acids and Salts; Biological Availability; Calcitriol; Excipients; Intestinal Absorption; Male; Phospholipids; Propylene Glycol; Rats; Rats, Sprague-Dawley; Sesame Oil; Solubility; Time Factors; Triglycerides; Tritium

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

U2 - 10.1002/jps.20403

DO - 10.1002/jps.20403

M3 - Journal article

C2 - 15986460

SN - 0022-3549

VL - 94

SP - 1830

EP - 1838

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

IS - 8

ER -