title: Determination of low levels of amorphous content in inhalation grade lactose by moisture sorption isotherms.
abstract: Alpha-lactose monohydrate is widely used as an excipient in dry powder inhalers, and plays a very important role in the efficiency of the drug delivery. Due to the processing, low levels of amorphous lactose could be present in the blends. Varying amounts could have a strong effect on the efficiency of drug delivery of the powder blends. Therefore, the accurate measurement of low levels of amorphous lactose content is very important. A new method was developed to measure the amorphous content, based on dynamic vapour sorption (DVS). In contrast to the traditional re-crystallization approach of amorphous lactose, the new method is based on moisture sorption isotherms. Moisture sorption isotherms of blends of crystalline alpha-lactose and freeze-dried or spray-dried amorphous lactose were measured. By fitting the data with a Brunauer, Emmett, and Teller (BET) isotherm, a linear correlation was found between measured and actual amorphous content for the whole range of 0.1-100%. Differences between freeze-dried and spray-dried lactose, due to different molecular arrangements, could be removed by a preconditioning the samples at 35% RH prior to the isotherm measurement. It was shown that accurate determination of very low concentrations of amorphous lactose content is possible using moisture sorption isotherm analyses.
authors.affiliation: FrieslandCampina Research, Harderwijkerstraat 41006, 7418 BA Deventer, The Netherlands.
authors.forename: Jasper
authors.initials: J
authors.lastname: Vollenbroek
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Hebbink
authors.forename: Susanne
authors.initials: S
authors.lastname: Ziffels
authors.forename: Hartwig
authors.initials: H
authors.lastname: Steckel
mesh_terms: D000280:Administration, Inhalation; D002138:Calibration; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004339:Drug Compounding; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry*; D005612:Freeze Drying; D006813:Humidity; D007785:Lactose / Q000008:administration & dosage / Q000737:chemistry*; D016014:Linear Models; D008956:Models, Chemical; D011208:Powders; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards; D014835:Volatilization; D014867:Water / Q000737:chemistry
chemical_list: D005079:Excipients; D011208:Powders; D014867:Water; D007785:Lactose