title: Stability improvement of a liquid enzyme product.
abstract: The shelf-life of a previously developed two-part liquid-liquid enzyme ceruminolytic product was improved maintaining the same final reconstituted composition and re-formulating the liquid enzyme portion as a drug granulate by a double wet granulation process. The critical steps for the preparation of the granulate were studied (mixing/granulating times and drying) determining the proteolytic activity, the residual ethanol, and the moisture content of the granulates. The original liquid-liquid formulation had been proven effective as a ceruminolytic agent, but only had stability of greater than 75% enzyme activity for up to 18 months and up to 1 day at room temperature after combining the two parts. The resulting improved product was proven to be stable for up to 24 months at 30 degrees C, and up to 3 days at room temperature after combining the two parts. Therefore, maintaining the enzyme in a granulated form until reconstitution afforded an improvement in stability compared with the original two-part liquid-liquid formulation.
authors.affiliation: Department of Pharmaceutical Development, Alcon R&D Laboratories, Camil Fabra 58, 08320, El Masnou, Spain. nuria.jimenez@alconlabs.com
authors.forename: Núria
authors.initials: N
authors.lastname: Jiménez
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Garcia
authors.forename: Javier
authors.initials: J
authors.lastname: Galán
authors.forename: Alberto
authors.initials: A
authors.lastname: Vallet
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Owen
authors.forename: G Michael
authors.initials: GM
authors.lastname: Wall
mesh_terms: D002626:Chemistry, Pharmaceutical; D004356:Drug Storage; D004795:Enzyme Stability; D012996:Solutions; D013678:Technology, Pharmaceutical
chemical_list: D012996:Solutions