PHYSICOCHEMICAL CHARACTERIZATION OF A POLYMERIC INJECTABLE IMPLANT DELIVERY SYSTEM

Citation
Ml. Shively et al., PHYSICOCHEMICAL CHARACTERIZATION OF A POLYMERIC INJECTABLE IMPLANT DELIVERY SYSTEM, Journal of controlled release, 33(2), 1995, pp. 237-243
Citations number
19
Categorie Soggetti
Pharmacology & Pharmacy",Chemistry
ISSN journal
01683659
Volume
33
Issue
2
Year of publication
1995
Pages
237 - 243
Database
ISI
SICI code
0168-3659(1995)33:2<237:PCOAPI>2.0.ZU;2-B
Abstract
Physico-chemical properties of an injectable polymeric implant system were evaluated and utilized to predict and understand the in vivo rele ase of a model drug. The injectable implant system is based on the pri nciple that a water insoluble polymer, dissolved in a biocompatible so lvent, will precipitate upon contact with water. The solubility parame ter of poly(dl-lactide) and DL-lactide-co-glycolide copolymers were ex perimentally determined by evaluating the solubility of these polymers in hydrogen bonding solvents having solubility parameters ranging fro m 8.9 to 14.8 (cal/cm(3))(1/2). The appropriate Flory-Huggins interact ion parameters were then calculated at 25 and 37 degrees C. Analysis o f ternary phase diagrams indicated that the quantity of water needed t o initiate precipitation, as well as the precipitation threshold, incr eased with increasing temperature in agreement with theoretical calcul ations. Rats were subcutaneously administered formulations comprised o f polymer concentrations above and below the precipitation threshold, i.e., 40% w/w polymer. Formulations with polymer concentrations below the precipitation threshold exhibited approximately twice the initial release compared to formulations having a polymer content above the pr ecipitation threshold. A key factor affecting the initial release of a model drug from formulations was the polymer content of the formulati on with respect to the precipitation threshold. The reported method of analysis may be utilized to screen polymers and biocompatible solvent s for use in these injectable implant systems.