Anti-hypertensive effect of oral controlled-release microspheres containing an ACE inhibitor (delapril hydrochloride) in rats.
An oral controlled-release drug delivery system based on microspheres of polyglycerol esters of fatty acids (PGEFs), was applied to an anti-hypertensive, delapril hydrochloride. The in-vitro release profile was controlled by selecting a PGEF with an appropriate hydrophilic-lipophilic balance value for the matrix. The microspheres from which 80% of the drug was released in 6 h were orally administered to rats. The plasma concentration of the active metabolite was sustained after administration of the microspheres in comparison with administration of a solution. The in-vivo release profile was in good agreement with the in-vitro release profile. When the microspheres were administered, the pharmacological effect of delapril hydrochloride on the angiotensin I-induced pressor response was also sustained showing consistency with the plasma concentration-time curve.
Akiyama
Y
Y
DDS Research Laboratories, Takeda Chemical Industries Ltd, Osaka, Japan.
Yoshioka
M
M
Horibe
H
H
Inada
Y
Y
Hirai
S
S
Kitamori
N
N
Toguchi
H
H
D000284:Administration, Oral; D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D003692:Delayed-Action Preparations; D005989:Glycerides / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007189:Indans / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008863:Microspheres; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013228:Stearates / Q000737:chemistry
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D005989:Glycerides; D007189:Indans; D011108:Polymers; D013228:Stearates; D000804:Angiotensin II; D000803:Angiotensin I; C047759:delapril