Journal of JPP 2002, 54: 1339–1344 # 2002 The Authors Received April 10, 2002 Accepted July 10, 2002 ISSN 0022-3573 Characterization of a surface modi ed dry powder inhalation carrier prepared by ‘‘particle smoothing’’ P. M. Young, D. Cocconi, P. Colombo, R. Bettini, R. Price, D. F. Steele and M. J. Tobyn Abstract Atomic force microscopy (AFM) was used to investigate drug–carrier interactions between beclometa- sone dipropionate (BDP) and a series of untreated and modi ed lactose surfaces. This quantitative information was correlated with bulk characterization methods and an in-vitro study. Modi ed lactose surfaces were prepared using a proprietary process referred to as ‘‘particle smoothing ’’ to obtain smooth carrier surfaces with or without the presence of magnesium stearate. The engineering of lactose carrier surfaces using the particle smoothing process resulted in signi cant differences in surface morphology when compared with the ‘‘as supplied ’’ starting material. The energy of separation, between BDP and lactose samples, determined by AFM suggested similar lognormal distributions with a rank decrease in median separation energy (e 0.5 ) (26.7, 20.6 and 7.7 J for untreated, particle-smoothed and particle-smoothed with magnesium stearate, respectively). A series of in-vitro twin stage impinger studies showed good correlation with the AFM separation energy measurements. The mean ne particle dose increased for the two processed lactose samples, with a signi cant increase for the lactose processed with magnesium stearate, 102.0 16 g compared with 24.2 10.7 g for the untreated lactose. Thus, the AFM presents as a possible pre-formulation tool for rapid characterization of particle interactions. Introduction The delivery of micron sized (sub 5 m) dry powder particulates to the respiratory tract, using dry-powder inhalers (DPI), has become commonplace in the prophylactic treatment of asthma and other bronchial related diseases. Drug particulates are often blended with larger (50± 200 m), inert crystalline carrier materials to form ordered mixes that, on inhalation, are liberated from the carrier to penetrate the lung. The e cacy of such a system is dependent on the interactive forces between the drug particulates and carrier. There are essentially three primary forces present in a dry powder inhalation system : van der Waals, electrostatic and capillary interactions. The magnitude of each of these forces, the total interaction, and subsequent aerolization e ciency will be dependent on the surface characteristics of the drug and carrier, and the environmental conditions in which they are stored and delivered. Previous investigations reported that the carrier morphology directly aOEects the aerolization e ciency from a DPI (Kawashima et al 1998 ; Podczeck 1998 ; Larhrib et al 1999 ; Zeng et al 2000). In general terms, a decrease in roughness is believed to improve aerolization e ciency of a drug± carrier blend. However, an important balance between the morphologies of both the drug and carrier can exist. For example, a tabular, atomically smooth carrier material and tabular micron sized drug particulate would most likely have a high carrier± drug interaction owing to an increased contact area. In contrast, a material with a roughness parameter slightly less than that of the drug would potentially lead to a decreased contact area and subsequent drug± carrier inter- actions. Another factor to consider is the surface free energy of the carrier. The use of low surface free energy materials, such as magnesium stearate or leucine (commonly used as lubricants in the tableting industry), has been reported as a possible means of increasing the aerolization e ciencies of such systems (Staniforth 1997). Pharmaceutical Technology Research Group, Department of Pharmacy and Pharmacology, University of Bath, BA2 7AY, UK P. M. Young, R. Price, D. F. Steele, M. J. Tobyn Chiesi Farmaceutici S.p.A., via Palermo, 43100 Parma, Italy D. Cocconi Department of Pharmacy, University of Parma, Area delle Scienze, 43100 Parma, Italy P. Colombo, R. Bettini Correspondence : Paul M. Young, Pharmaceutical Technology Group, Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, UK. E-mail : prppmy!bath.ac.uk 1339