Direct adhesion measurements of pharmaceutical particles to gelatin capsule surfaces

Abstract Scanning probe microscopy (SPM) was used to measure directly the adhesion of individual lactose particles to the surface of gelatin capsules employed in dry powder inhalant drug delivery systems. In this study, SPM shows that gelatin capsule surfaces with high surface heterogeneity and high-contrast friction exhibit high adhesion and that gelatin capsule surfaces with low surface heterogeneity and low-contrast friction exhibit low adhesion. The adhesion of lactose particles to gelatin capsules was also determined by measuring the retention of lactose particles in the capsules. The adhesion trend obtained with individual lactose particles using the colloidal probe technique agrees with the macroscopic retention results. The adhesion appears to be proportional to the particle size for homogeneous capsule surfaces. In dry powder inhalation products, the Lifshitz-van der Waals forces and acid-base interactions appear to be the principal forces contributing to particle-surface adhesion. The physicochemical nature of the capsule surface seems to dictate the spatial variation of adhesion across the surface. The SPM results clearly show that the surface physicochemical properties depend on the gelatin and mold release agent utilized in the manufacture of gelatin capsules. One of the practical implications of this study is that extraneous surface contamination of gelatin capsules by chemical processing aids such as mold release agents appears to be a key factor affecting the respirable fraction in dry powder inhalation products. Keywords: ADHESIONATOMIC FORCE MICROSCOPYCOLLOIDAL PROBEFRICTION IMAGINGLACTOSEGELATIN CAPSULEPARTICLE-SURFACE ADHESIONPHARMACEUTICAL INHALATION PRODUCTSSCANNING PROBE MICROSCOPY