Novel Approach to DPI Carrier Lactose with Mechanofusion Process with Additives and Evaluation by IGC

• Published in: Chemical & Pharmaceutical Bulletin Vol. 54; no. 11; pp. 1508 - 1514
• Main Authors: Michiko KUMONa, Masahiko SUZUKIa, Akira KUSAIa, Etsuo YONEMOCHIb, Katsuhide TERADAb
• Format: Journal Article
• Language: Japanese
• Published: Pharmaceutical Society of Japan 2006
• ISSN: 0009-2363

The effect of lactose carrier surface property on the inhalation profile of dry powder inhaler (DPI) was eval-uated using a micronized drug (Compound A) by inverse gas chromatography (IGC). Mechanofusion with magnesium stearate (Mg-St) or sucrose stearate increased the line particle fraction (FPF), considered to be due to de-crease 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 in-creased as both the dispersive component of the surface energy and acidity similarity between the lactose carri-ers 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.