title: Effect of pepsin on maintaining the supersaturation of the HCl salt of a weakly basic drug: a case study.
abstract: The impact of pepsin on the maintenance of supersaturated solution of the HCl salt of a weakly basic drug was evaluated in simulated gastric fluid by monitoring the drug solubility in the absence and presence of pepsin. In the presence of pepsin, the HCl salt maintained its apparent solubility through 24 h, whereas, no such solubility advantage was seen in the absence of pepsin. Consequently, a minimum inhibitory concentration of pepsin is required for maintenance of supersaturation. In addition, NMR study seems to indicate a molecular level interaction between pepsin and HCl salt leading to a weak binding between the two. Therefore, for the HCl salts of weak bases having disproportionation potential, it is preferred that preformulation solubility studies are conducted in the presence of pepsin to reflect their in vivo behavior in maintaining supersaturation solubility.
authors.affiliation: a Drug Product Science and Technology and.
authors.forename: Swathi
authors.initials: S
authors.lastname: Pinnamaneni
authors.affiliation: b Analytical and Bioanalytical Development, R&D, Bristol-Myers Squibb Co. , New Brunswick , NJ , USA.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Rinaldi
authors.affiliation: b Analytical and Bioanalytical Development, R&D, Bristol-Myers Squibb Co. , New Brunswick , NJ , USA.
authors.forename: Dimuthu A
authors.initials: DA
authors.lastname: Jayawickrama
authors.affiliation: a Drug Product Science and Technology and.
authors.forename: Jinjiang
authors.initials: J
authors.lastname: Li
authors.affiliation: a Drug Product Science and Technology and.
authors.forename: Mandar V
authors.initials: MV
authors.lastname: Dali
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D006851:Hydrochloric Acid / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D010434:Pepsin A / Q000737:chemistry*; D019999:Pharmaceutical Solutions / Q000737:chemistry*; D012995:Solubility
chemical_list: D019999:Pharmaceutical Solutions; D010434:Pepsin A; D006851:Hydrochloric Acid
keywords: Precipitation inhibitor; simulated gastric fluid; supersaturation