Journal of Controlled Release, 12 (1990) 121-132 Elsevier Science Publishers B.V., Arns~r~ - Printed in The Netherlands 121 THE RELATIONSHIP BETWEEN DRUG RELEASE RATE, PARTICLE SIZE AND SWELLING OF SILICONE MATRICES Gershon Golomb*, Paula Fisher The Hebrew University of Jerusalem, Department of Pharmacy, School of Pharmacy, P.O. Box 12065, Jerusalem 9 1720 [israel) and Ezra Rahamim Electron Microscope laboratory, The Hebrew University of Jerusalem, Jerusalem (Israel) (Received March 1, 1989; accepted in revised form August 14, 1989) Key words: silicone matrices; implantable systems; drug release rate Matrices composed of silicone elastomer (polydimethylsiloxane) have been used extensively as implantable controlled release drug delivery systems. This study examined the relationship be- tween drug particle size, release rate and swelling of silastic matrices, by using a model drug (potassium di~h~mate~ and two types of silicone polymer. The drug particles were found to be the drivi~ force for water uptake by the ~tr~. The release rate was dire~tlyp~~~~~l to the degree of swe~i~, which in turn was directly propo~~~l to the dr~~rt~~ size. The release rate and swelling of matrices composed of silastic 382 increased with decreasing dr~~rt~~ size, white increasing drug particle size resulted in increased release rate and decreased swelling of silastic Q7 matrices, probably because air is entrapped during fabrication of these matrices. More retarded release and swelling was exhibited by silastic Q7 matrices in comparison to matrices composed of silastic 382, probably due to the different physical properties of these silicones. INTRODUCTION Matrices composed of poly~methylsiloxane (silastic) have been used extensively as im- plantable controlled release drug delivery sys- tems. We have recently shown [ 1,2] that effec- tive anticalcification therapy of bioprosthetic heart valve calcification was achieved by using implantable, silastic-based controlled release matrices containing sodium and/or calcium salts of hydroxyethylidene bisphosphonate. The silastic matrix is a two phase system consisting of a continuous phase of polymer carrier and a dispersed phase of drug powder particles rang- *To whom correspondence should be addressed. ing in size from several tens to several hundreds of micrometres. Several studies [l-8] have suggested that the release mechanism of a dispersed drug in a hy- drophobic, non-degradable and insoluble poly- meric matrix is as follows. Water diffuses into the matrix through both the hydrophobic and hydrophilic phases (polymeric and dispersed drug phases, respectively), dissolving the drug. Once the surface layer of drug powder particles is released, pores are left in the matrix, and ad- ditional drug particles can therefore diffuse out through the developed pore network. Thus, a higher release rate is observed at higher drug loadings and solubility, because more pores are developed in the matrix, and at a higher rate. 0168-3659/90/$03.50 0 1990 Elsevier Science Publishers B.V.