Development of solid SEDDS, VII: Effect of pore size of silica on drug release from adsorbed self-emulsifying lipid-based formulations.

PURPOSE: Lipid-based self-emulsifying drug delivery systems (SEDDS) are usually liquids, and they can be converted into solid dosage forms by adsorbing onto silicates. However, most commercially available silicates are mesoporous with small pore sizes of 1 to 50nm that lead to incomplete emulsification of SEDDS inside the pores and thus incomplete drug release. The objective of this study was to investigate the impact of silica pore size on the extent of drug release from SEDDS solidified by adsorbing onto macroporous silicas with different pore sizes.

METHODS: Silicas with average pore sizes of approx. 150nm, 500nm and 5μm were synthesized using the colloidal crystal templating method. A model poorly water-soluble drug, probucol, was dissolved in liquid SEDDS containing different lipid to surfactant ratios, and the formulations were then adsorbed onto equal weights of silicas (1:1 w/w ratio). Drug release from freshly prepared formulations and after storing at 40°C/60% RH for up to 6months was studied using a modified USP type 2 method with mini paddles and 50mL of 0.01M HCl (pH~2) at 37°C. Drug release was also studied similarly from silicas that were precoated with PVP K-30 at 5, 10, 20 and 30% w/w levels before adsorption of SEDDS.

RESULTS: Freshly prepared formulations containing relatively higher lipid:surfactant ratio of 7:3% w/w exhibited 17, 40 and 60% drug release from uncoated (neat) silicas with pore sizes of 150nm, 500nm and 5μm, respectively, while the more hydrophilic formulations containing 3:7 w/w lipid:surfactant ratio had, respectively, 50, 65 and 85% drug release. No decrease in drug release was observed when the formulations were exposed to 40°C/60% RH for up to 6months. When the silicas were precoated with 20% PVP, the drug release was almost complete (>80%), which remained unchanged even after 6months of storage irrespective of the composition of adsorbed liquid SEDDS.

CONCLUSIONS: Both pore size and composition of SEDDS had major impacts on drug release from silicas. Increased drug release was observed with the increase in pore size of silicas and hydrophilicity of formulations. Since the silicas synthesized were macroporous with no mesopores present, there was no decrease in drug release upon storage. Complete drug release was observed when silicas were precoated with PVP as it increased the penetration of water into the pores.