In vivo characteristics of low molecular weight copoly (D,L-lactic acid) formulations with controlled release of LH-RH agonist.
Amorphous and crystalline copolymers with a relatively low molecular weight of 1800 were synthesized by direct copolycondensation of D-lactic acid and L-lactic acid in the absence of a catalyst, to evaluate their in vivo capabilities as biodegradable carriers for drug delivery systems. A luteinizing hormone-releasing hormone agonist, des-Gly10-(D-Leu6)-LH-RH ethylamide, was incorporated in a fine cylindrical copolymer formulation, under melt-pressing technique, a mild heat-pressure condition. This formulation was implanted subcutaneously in the back of male rats. The rate of in vivo degradation of amorphous copolymer was much faster than that of crystalline copolymer. Contrary to this tendency, the in vivo release of the drug from this amorphous formulation was held constant over a longer period, compared with the crystalline formulation. This can be closely related to the difference in dispersion of the drug in the formulation.
Asano
M
M
Department of Development, Japan Atomic Energy Research Institute, Gunma.
Fukuzaki
H
H
Yoshida
M
M
Kumakura
M
M
Mashimo
T
T
Yuasa
H
H
Imai
K
K
Yamanaka
H
H
D000818:Animals; D001673:Biodegradation, Environmental; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D003692:Delayed-Action Preparations; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000097:blood; D007773:Lactates; D019344:Lactic Acid; D016729:Leuprolide; D008297:Male; D008970:Molecular Weight; D011091:Polyesters; D011108:Polymers; D019736:Prostheses and Implants; D051381:Rats; D011919:Rats, Inbred Strains; D013053:Spectrophotometry; D013997:Time Factors
D003692:Delayed-Action Preparations; D007773:Lactates; D011091:Polyesters; D011108:Polymers; D007987:Gonadotropin-Releasing Hormone; D019344:Lactic Acid; C033616:poly(lactide); D016729:Leuprolide