Effects of Formulation and Manufacturing Process on Drug Release from Solid Self-emulsifying Drug Delivery Systems Prepared by High Shear Mixing.

Abstract

This study sought to investigate the influence of formulation and process factors of the high shear mixing (HSM) on the properties of solid self-emulsifying drug delivery systems (S-SEDDS) containing the model drug carvedilol (CAR). Firstly, liquid SEDDS (L-SEDDS) were prepared by mixing castor oil with different proportions of surfactant (Solutol or Kolliphor RH40) and cosolvent (Transcutol or PEG400). A miscible L-SEDDS with high drug solubility (124.3mg/g) was selected and gave rise to 10% (m/m) CAR loaded-emulsion with reduced particle size. Then, a factorial experimental design involving five component's concentration and two process factors was used to study the solidification of the selected L-SEDDS by HSM. CAR content, diffractometric profile, and in vitro dissolution were determined. Morphological and flow analyses were also performed. Porous and spherical particles with mean sizes ranging from 160 to 210µm were obtained. Particle size was not affected by any formulation factor studied. Powder flowability, in turn, was influenced by L-SEDDS and crospovidone concentration. CAR in vitro dissolution from S-SEDDS was significantly increased compared to the drug as supplied and was equal (pH 1.2) or lower (pH 6.8) than that determined for L-SEDDS. Colloidal silicon dioxide decreased drug dissolution, whereas an increase in water-soluble diluent lactose and L-SEDDS concentration increased CAR dissolution. The proper selection of liquid and solid constituents proved to be crucial to developing an S-SEDDS by HSM. Indeed, the results obtained here using experimental design contribute to the production of S-SEDDS using an industrially viable process.