Enhanced dissolution rate of nimodipine through ?-lactoglobulin based formulation

Amorphous solid dispersions (ASD) have been considered as one of the most effective strategies to increase solubility and dissolution rate of poorly water-soluble drugs. Carriers, in which the poorly water-soluble drug is dispersed, contribute a large extent to the solid-state properties, stabilities and dissolution performance of ASDs. This study investigated the solid-state properties, physical stability, and in vitro dissolution behaviour of nimo-dipine ASDs formulated with a traditional polymeric carrier, i.e., polyvinylpyrrolidone (PVP) and a novel carrier, i.e., beta-lactoglobulin (BLG). The ASDs with both carriers were prepared using ball milling as preparative technique at 10 %, 17.5 %, 25 %, 30 % and 40 % drug loadings (DLs). All the formulations were found to be amorphous upon milling for 60 min based on X-ray powder diffraction measurements, however, the ASDs were found to be homogeneous unequivocally only at DLs below 25 %. After open storage at accelerated conditions (40 degrees C/75 % relative humidity), only the ASDs formulated with BLG at 10 % and 17.5 % DLs maintained the amorphous form. The dissolution study revealed that all the freshly prepared ASDs formulated with PVP and the ASDs formulated with BLG at or above 25 % DLs, showed a low drug release (<30 mu g/mL in simulated gastric fluid, < 70 mu g/mL in simulated intestinal fluid). Whilst the ASD formulated with BLG at 10 % DL exhibited a high drug release with a maximum concentration (Cmax) of 251 mu g/mL in simulated gastric fluid and 231 mu g/mL in simulated intestinal fluid. Surprisingly, the ASD formulated with BLG at 17.5 % DL demonstrated an even higher drug release (Cmax, 643 mu g/mL in simulated gastric fluid, 332 mu g/mL in simulated intestinal fluid), compared to the ASD of 10 % DL. These findings underline the importance of rationally investigating both carrier types and DL in the design of ASDs, in order to obtain a stable ASD with the desired enhanced dissolution rate of poorly water-soluble drugs.

Automated summary

Amorphous solid dispersions (ASDs) are effective strategies to enhance the solubility and dissolution rate of poorly water-soluble drugs. This study compared two carriers, polyvinylpyrrolidone (PVP) and beta-lactoglobulin (BLG), in the formulation of nimo-dipine ASDs. It was found that only ASDs with DLs below 25% were homogeneous and BLG carriers at 10% and 17.5% DLs maintained their amorphous form after storage. Additionally, BLG ASDs at 10% and 17.5% DLs exhibited higher drug release compared to PVP ASDs and BLG ASDs at higher DLs.