Journal of Controlled Release, 16 ( 1991) 341- 348 0 1991 Elsevier Science Publishers B.V. 0168-3659/91/$03.50 ADONIS016836599100035P 341 COREL 006 11 Base-induced polymer hydrolysis in poly (b-hydroxybutyratel hydroxyvalerate) matrices Sumie Yoshioka, Akio Kishida, Satoshi Izumikawa, Yukio Aso and Yasushi Takeda National Institute of Hygienic Sciences, Kamiyoga. Setagaya-ku, Tokyo, Japan (Received August 20, 1990; accepted in revised form December 12, 1990) Polymer hydrolysis in base-loaded poly(j3-hydroxybutyrate/jI-hydroxyvalerate) films was studied using clonidine, indenolol, thioridazine and cinnaridine as model bases. The hydrolysis was followed by determining the molecular weight distribution of the polymer by means of a gel permeation chro- matograph coupled with a low-angle laser light-scattering photometer. The water and carboxylic acid contents in films were also determined as a function of time. The hydrolysis rate depended on the basicity and loading amount of incorporated bases. A significant change in the molecular weight of PHB-PHV was brought about by a relatively small amount of water present in films. The hydrolysis rate was governed by water solubility and polymer/water partition of incorporated bases, and corre- sponded with the diffusion rate of water in films. The drug release rates from PHB-PHV matrices were accelerated by the base-induced hydrolysis of PHB-PHV. In viva hydrolysis of PHB-PHV in films was also induced by incorporation of bases. The results suggest that the base-induced hydrolysis of PHB- PHV matrices can be applied to control the polymer hydrolysis rate and drug release rate of drug deliv- ery system made of PHB-PHV which is hardly hydrolyzed under physiological conditions. Keywords: Poly (/3-hydroxybutyratelhydroxyvalerate); Biodegradable polymer; Hydrolysis; Release rate; Degradation; Molecular weight distribution Introduction Poly (&hydroxybutyrate//3-hydroxyvaleate (PHB-PHV) has been discussed as biodegrada- ble systems for drug delivery and medical de- vices [ l-41. Such polymers should, ideally, be degraded in vivo and resorbed by the body after their particular functions such as drug release are completed. Biodegradation of PHB-PHV, how- ever, is known to be very slow under physiologi- cal conditions, suggesting a considerably long re- tention in the body. Control of the Correspondence to: S. Yoshioka, National Institute of Hygienic Sciences, 1- 18- 1, Kamiyoga, Setagaya-ku, Tokyo 158, Japan. biodegradation rate is desired for applications of the polymer to drug delivery systems or medical implantable devices. It has been reported that the degradation of poly (L-lactic acid), poly (D,L-lactic acid) and zyxwvut poly (glycolic acid/L-lactic acid) is accelerated by basic drugs loaded in microspheres [ 5,6]. In the previous paper we reported that degradation rates of polyester matrices can be controlled by incor- porating a suitable amount of basic compounds having a suitable basicity [ 7 1. The present paper describes the effect of base-incorporation on the in vitro and in vivo degradation of PHB-PHV matrices which are, per se, hardly hydrolyzed under physiological conditions. The mecha-