Silicone matrices loaded with levonorgestrel particles: Impact of the particle size on drug release

Particle size reduction can increase dissolution rate of partially soluble drugs, due to the subsequent increase in their specific surface area, though with some exceptions. Nanoparticulation may enhance successive release rate from monolithic delivery devices when dissolution in surrounding polymer matrix is the rate limiting step. Here, levonorgestrel (LNG) particle size was reduced by a novel O/W (organic phase/water) microemulsification-solvent evaporation method. The optimal conditions for microemulsification were obtained using Tween 80 (8% (w/v)) as a surfactant, n-propanol (2.3% (w/v), relative to external phase volume) as a co-surfactant, methylene chloride (containing 3% (w/v) of LNG) and aqueous PVP solution (about 3% (w/v)) as the external phase. Particle size analysis of the resulting LNG particles by laser light scattering and scanning electron microscopy showed nano-sized particles with mean particle size of 39 +/- 3 nm after solvent evaporation. Mean particle size increased to 292 +/- 4 nm after freeze drying. Nano-sized particles were loaded into a silicone rubber matrix and LNG release profile was investigated in comparison to neat micron-sized LNG particles. Devices containing nano-sized particles exhibited the same diffusional pattern for drug release profile as their counterpart micron-sized LNG-loaded devices. However, drug release percentage was increased significantly by particle size reduction for samples loaded with 0.25% (w/w) LNG. The devices were made porous by a salt (sodium chloride 10% (w/w)) leaching method which enhanced LNG release percentage by increasing the specific surface area of the devices in contact to release medium. In this way, cumulative amount of LNG released from the silicone rubber matrix and its corresponding percentage were both increased by adding a porogen, especially for nano-sized, LNG loaded devices.