title: Novel approach to DPI carrier lactose with mechanofusion process with additives and evaluation by IGC.
abstract: The effect of lactose carrier surface property on the inhalation profile of dry powder inhaler (DPI) was evaluated using a micronized drug (Compound A) by inverse gas chromatography (IGC). Mechanofusion with magnesium stearate (Mg-St) or sucrose stearate increased the fine particle fraction (FPF), considered to be due to decrease in the interaction between Compound A and the lactose carrier. The effect of Compound A concentration on FPF was smaller in mechanofusion-processed lactose compared to intact lactose, especially when processed with Mg-St. The relationship between the IGC parameters of the lactose and FPF was also investigated. FPF increased as both the dispersive component of the surface energy and acidity similarity between the lactose carriers and Compound A increased. Although further investigation is necessary, it could be suggested that acidity similarity decreases the interaction between Compound A and lactose, thus contributing to the increase in the FPF. In conclusion, (1) mechanofusion with Mg-St or sucrose stearate could be an effective method to improve FPF of a DPI drug formulation; (2) IGC would be a valuable method to investigate the interaction between a drug and the DPI carrier; and (3) a relationship between surface acidity and inhalation profile was suggested.
authors.affiliation: Pharmaceutical Development Laboratories, Sankyo Co., Ltd., Hiratsuka, Kanagawa, Japan. kumonn@sankyo.co.jp
authors.forename: Michiko
authors.initials: M
authors.lastname: Kumon
authors.forename: Masahiko
authors.initials: M
authors.lastname: Suzuki
authors.forename: Akira
authors.initials: A
authors.lastname: Kusai
authors.forename: Etsuo
authors.initials: E
authors.lastname: Yonemochi
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Terada
mesh_terms: D002849:Chromatography, Gas / Q000295:instrumentation / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004867:Equipment Design; D004987:Ethers / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D007785:Lactose / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning / Q000379:methods; D010316:Particle Size; D011208:Powders; D012680:Sensitivity and Specificity; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; D004987:Ethers; D006845:Hydrocarbons, Fluorinated; D011208:Powders; C078742:fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether; D007785:Lactose