A new combination approach of CI jet and QESD to formulate pH-susceptible amorphous solid dispersions

作者：Kumar Sumit; Linehan Brian; Tseng Yin Chao^*

来源：International Journal of Pharmaceutics, 2014, 466(1-2): 368-374.

DOI：10.1016/j.ijpharm.2014.03.042

• Amorphous
• pH-susceptible
• Solubility enhancement
• Solid dispersion
• DoE

A new combination approach of quasi-emulsion solvent diffusion (QESD) and confined impinging jet (CIJ) technologies was utilized to formulate pH-susceptible amorphous solid dispersions (ASDs) of a poorly soluble investigational compound (BI906) of Boehringer Ingelheim Pharmaceuticals. The objective of this study was to formulate small-size pH-susceptible ASDs of BI906 to enhance its dissolution and solubility. A design of experiment approach was utilized to study the influence of critical parameters: antisolvent-to-solvent ratio, stabilizer concentration, polymer-to-drug ratio and flow rate of solvent. The critical quality attributes of the pH-susceptible solid dispersions (SDs) were crystallinity, particle size, drug loading and dissolution. The particle size of SDs was dependent on the antisolvent-to-solvent ratio, polymer-to-drug ratio and solvent flow rate. An increase in the solvent flow rate and antisolvent-to-solvent ratio resulted in smaller particle size of SDs. It was observed that the drug crystallinity and drug release were dependent on the polymer-to-drug ratio. The formulations containing a polymer-to-drug ratio of 6:1 were amorphous and showed superior pH dependent in vitro drug release performance. This study demonstrates that this new combination approach is feasible to formulate small-size pH-susceptible ASDs and it can be applied to other poorly soluble drugs to enhance in vitro dissolution and solubility. Published by Elsevier B.V.

• 出版日期2014-5-15