title: A new combination approach of CI jet and QESD to formulate pH-susceptible amorphous solid dispersions.
abstract: 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.
authors.affiliation: University of Connecticut, School of Pharmacy, Storrs, CT 06269, United States.
authors.forename: Sumit
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Linehan
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, United States. Electronic address: yin-chao.tseng@boehringer-ingelheim.com.
authors.forename: Yin-Chao
authors.initials: YC
authors.lastname: Tseng
mesh_terms: D000096:Acetone / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004058:Diffusion; D006863:Hydrogen-Ion Concentration; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008752:Methylene Chloride / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations; D012997:Solvents; D000096:Acetone; D008752:Methylene Chloride; D008747:Methylcellulose; C053309:hydroxypropyl methylcellulose phthalate
keywords: Amorphous; DoE; Solid dispersion; Solubility enhancement; pH-susceptible