IMPROVED AQUEOUS DISSOLUTION OF NIMODIPINE USING SELF-MICROEMULSIFYING SOLID COMPOSITIONS

Abstract

Nimodipine is a highly lipophilic calcium channel blocker presenting extremely low aqueous solubility. This study aimed to develop solid self-microemulsifying tablets (SSMETs) that can considerably increase the apparent aqueous solubility and dissolution of nimodipine. For the selection of proper components of liquid state self-microemulsifying formulations (LSMEFs), nimodipine solubility and emulsification capability were evaluated. Based on these two factors, Capryol (TM) 90, Cremophor (R) EL, and polyethylene glycol 400 (PEG 400) were chosen as oil, surfactant, and co-surfactant, respectively. The optimized LSMEF was then established through the construction of pseudo-ternary phase diagrams. Next, to solidify the optimized LSMEF, several adsorbents were screened, and the LSMEF solidified with Neusilin (R) UFL2 showed the highest dissolution profile with an appropriate solvent binding capacity. To further facilitate the drug release from the SSMETs, several disintegrants were investigated, and the SSMET containing Primellose (R) as a disintegrant substantially increased the dissolution of nimodipine. In addition, when the SSMET re-dispersed in simulated intestinal fluid, the SSMET successfully formed microdroplets presenting similar small size (similar to 90 nm) to droplets dispersed from the LSMEF. These results demonstrated that this SSMET we designed is a promising drug delivery system for poorly soluble drugs, such as nimodipine.