Drug–lactose binding aspects in adhesive mixtures: Controlling performance in dry powder inhaler formulations by altering lactose carrier surfaces ☆ Qi (Tony) Zhou, David A.V. Morton ⁎ Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville campus), 381 Royal Parade, Parkville, VIC 3052, Australia abstract article info Article history: Received 10 February 2011 Accepted 7 July 2011 Available online 18 July 2011 Keywords: Dry powder inhaler Lactose carrier Adhesive mixture Aerosol performance Force control agents Cohesive–adhesive balance Surface modification Mechanical dry powder coating Surface coating characterization For dry powder inhaler formulations, micronized drug powders are commonly mixed with coarse lactose carriers to facilitate powder handling during the manufacturing and powder aerosol delivery during patient use. The performance of such dry powder inhaler formulations strongly depends on the balance of cohesive and adhesive forces experienced by the drug particles under stresses induced in the flow environment during aerosolization. Surface modification with appropriate additives has been proposed as a practical and efficient way to alter the inter-particulate forces, thus potentially controlling the formulation performance, and this strategy has been employed in a number of different ways with varying degrees of success. This paper reviews the main strategies and methodologies published on surface coating of lactose carriers, and considers their effectiveness and impact on the performance of dry powder inhaler formulations. © 2011 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275 2. Engineering of surface morphological properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276 2.1. Smooth lactose carrier surfaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276 2.2. Rough lactose carrier surfaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276 3. Surface coating of lactose carrier . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277 3.1. Solvent-based coating . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277 3.2. Mechanical dry coating . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277 3.2.1. Mechanofusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278 3.2.2. Theta-composer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279 3.3. Other coating strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281 3.4. Characterization of the coating quality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281 4. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281 5. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283 Acknowledgement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283 1. Introduction The performance of dry powder inhaler (DPI) formulations can be a strong function of the balance of cohesive and adhesive forces experienced by the drug particles [1]. In this article we consider the most common DPI formulation approach, consisting of an adhesive mixture of micronized drug with lactose carriers acting as a flow and fluidization aid. However it has been shown that in some formulations, a further excipient additive (for example, additional fine lactose or magnesium stearate) where included, can act as a de-agglomeration facilitator or force control agent [2]. Lactose has been adopted as the safe excipient of choice for pulmonary delivery [3]. The form of lactose used in such formulations Advanced Drug Delivery Reviews 64 (2012) 275–284 ☆ This review is part of the Advanced Drug Delivery Reviews theme issue on “Lactose as a Carrier for Inhalation Drug Delivery”. ⁎ Corresponding author. Tel.: + 61 3 99039523; fax: 61 3 99039583. E-mail address: david.morton@monash.edu (D.A.V. Morton). 0169-409X/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.addr.2011.07.002 Contents lists available at ScienceDirect Advanced Drug Delivery Reviews journal homepage: www.elsevier.com/locate/addr