oa Mechanistic Release Study of Water Soluble Drugs from Poly (Dimethylsiloxanes) Elastomeric Matrices

Introduction: Controlled drug release from implantable silicone elastomers was reported to occur mainly via the osmotic rupture release mechanism. In this work, we are attempting to determine the effects of drug volumetric loading, particle size, device shape, and dissolution media on the release rate of the water-soluble osmotically active drug, Papaverine Hydrochloride (PH) from silicon elastomers.

Materials and Methods: Medical grade silicone (Sylgard kit) was purchased from Dow Corning. All other chemicals were purchased from Sigma-Aldrich and used as received. The release profiles from devices of three geometries (cylinders, cubes and tablets), of different drug particle sizes (< 45μm, 63–125μm or 125–250μm) in different dissolution media (phosphate buffered saline, distilled water, and 3% sodium chloride solution) were investigated. The effect of degree of elastomer crosslinking and the percentage of volumetric loading of the osmotic excipient and pore forming agent, Trehalose, on the release rate were also investigated. The drug fraction released of PH was analyzed using ultraviolet spectrophotometric analysis. Data obtained was then plotted as cumulative percentage release against time and then further analyzed.

Results and Discussion: Contrary to previous reports, devices formulated with the same volumetric loading and smaller drug particles sizes released drug faster than those devices with a larger particle size. The drug release from tabular implants was of faster rate when compared to cylindrical and cubic devices. Contrary to the expected, higher drug release rate was also observed from cubic elastomeric devices with higher crosslinking density. In addition, the release profiles demonstrated that osmotic release was the predominant mechanism governing the release of PH from silicone elastomers.

Conclusion: Our results show that osmotic rupture is the predominant mechanism of release of PH from silicone elastomer. Further studies must be conducted to confirm the effect of the elastomer crosslinking density on drug release rate.

Acknowledgements: This report was made possible by a UREP award [UREP 07-120-3-027] to HM Younes from the Qatar National Research Fund (a member of The Qatar Foundation). The statements made herein are solely the responsibility of the authors.