Application of spray granulation for conversion of mixed phospholipid-bile salt micelles to dry powder form: Influence of drug hydrophobicity on nanoparticle reagglomeration

Abstract

The aim of this study was to investigate the feasibility of using spray granulation as a drying method to convert phospholipid (PL)-sodium deoxycholate (SDC)-mixed micelles (MMs) containing a water-insoluble drug to a solid dosage form and to evaluate how drugs with significantly different physicochemical properties affect the spray granulation process and subsequent in vitro and in vivo processes. Cucurbitacin B (Cu B) and glycyrrhizin (GL) were used as the model drugs. After spray granulation, the dried Cu B-PL/SDC-MM powder was completely redispersible within 15 minutes in vitro. Meanwhile, the area under the curve during 24 hours (AUC0-24) and peak serum concentration from the dried powder were significantly (P<0.05) lower than the values from Cu B-PL/SDC-MMs in vivo. However, a better result was obtained for GL, ie, the drug was redispersed completely within 5 minutes in vitro. Further, absorption from the dried GL-PL/SDC-MM powder was increased to the same level as that for GL-PL/SDC-MMs in vivo compared with the control group. The difference in these results can be found in Cu B and GL. Cu B nanoparticles reagglomerated when released, resulting in slower redispersibility and less absorption compared with the original PL-SDC-MMs. However, no agglomeration or delay was observed for GL. A possible explanation is the difference in surface hydrophobicity between Cu B and GL. The results of this study not only show that spray granulation is an effective drying technique that can complement spray-drying and freeze-drying, but also confirm that the physicochemical properties of a drug have a significant influence on the in vitro and in vivo performance of the dried powder obtained after spray granulation. © 2014 Lv et al.