Improvement by adjuvants on the rectal bioavailability of non-absorbable drugs following administration of suppository.
The influence of suppository bases and adjuvants on the release rate of drugs and the absorption of non-absorbable drugs such as sulfanilic acid (SA) and sulfaguanidine (SG), was investigated following the rectal administration of suppositories. The suppository bases used were lipophilic bases such as Witepsol W 35, H 15, S 55, E 75 and hydrophilic base such as macrogol. SA was rapidly released from macrogol, W 35, H 15 and S 55, except E 75. On the other hand, SG was rapidly released from macrogol, whereas the release of SG from lipophilic bases was slow. Rectal absorption of SA and SG following administration of each drug alone in suppository form was slight. On the addition of diclofenac sodium (DF) as absorption promoter the blood levels of SA and SG released from all suppositories increased by about two to four fold compared with those suppositories containing only SA or SG, respectively. However, the absorption of SG still did not attain sufficient levels by the administration of DF only. The rectal absorption of SG was markedly increased by the release rate of the drug from the suppository. These results indicate that after administration of these suppositories the bioavailability of non-absorbable drugs was sufficiently improved by enhancing both the release rate from the suppositories and the rectal membrane permeability.
Nakanishi
K
K
Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
Masada
M
M
Nadai
T
T
D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology*; D000285:Administration, Rectal; D000818:Animals; D001682:Biological Availability; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012007:Rectum / Q000378:metabolism*; D013414:Sulfaguanidine / Q000008:administration & dosage / Q000493:pharmacokinetics; D013425:Sulfanilic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics; D013488:Suppositories / Q000493:pharmacokinetics*
D000277:Adjuvants, Pharmaceutic; D013425:Sulfanilic Acids; D013488:Suppositories; D013414:Sulfaguanidine; C100016:4-sulfanilic acid