The role of drug lipophilicity in release from intra-adipose and intramuscular injection sites.
Release rates from intramuscular and intra-adipose injection sites are dependent upon several including injection depth. Little is known about the relationship between drug lipophilicity and transport rate of drugs through adipose and muscle tissue. The principal objective of the present study was to investigate to what extend drug lipophilicity affects release and release rate from adipose tissue. Nine pigs were given intravenous (0.1 mg/kg), intramuscular (0.2 mg/kg) and intra-adipose (0.2 mg/kg) injections of propranolol, alprenolol, carazolol, metoprolol and atenolol. The fraction not-absorbed versus time plots after intramuscular and intra-adipose injection showed a biphasic decline for all model compound with the exception of atenolol being the most hydrophilic drug. This biphasic decline indicates that two different mechanisms may be involved in drug release. Initial release rates after intra-adipose injection were negatively correlated (Kendall's rankorder test) with fat-buffer distribution constants. The extent of release after 24 h could be considered as a characteristic parameter for the second release phase. The amounts released after 24 h were lower for propranolol, alprenolol, carazolol and metoprolol than for atenolol. Incomplete release at 24 h can be explained by the decrease of the solvent drag after absorption of the vehicle is complete.
Kadir
F
F
University of Utrecht, Department of Pharmaceutics, The Netherlands.
Zuidema
J
J
Pijpers
A
A
Vulto
A
A
Verheijden
J H
JH
D000273:Adipose Tissue; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D007267:Injections; D007273:Injections, Intramuscular; D008055:Lipids; D013552:Swine
D000319:Adrenergic beta-Antagonists; D008055:Lipids