Erythromycin acistrate

Particle morphology of pharmaceutical solids has practical importance for several reasons. In particular, surface roughness can influence formulation development and pharmaceutical performance for a wide range of delivery types including oral tablets and dry powder formulations for inhalation. For instance, the surface roughness can influence dissolution, friability, and adhesion of coatings and films for bare tablets (1–5). To illustrate, surface roughness correlated strongly with tablet friability for erythromycin acistrate tablets (3). The surface roughness has also been related to gloss and permeability, such that the reflectivity and surface texture of coated tablets were directly correlated (6,7). The surface roughness of particles also has been correlated to powder flow and powder packing (8), where the smoother particles led to an improvement of powder packing and flow properties. The adhesion of particles to surfaces or other particles can also be greatly affected by surface roughness. This is of particular concern for dry powder inhalation (DPI) formulation development. Dry powder formulations are often composed of small drug particles and inert larger carrier particles. Interactions between these particles can be dominated by physico-chemical properties of the particle, such as size, shape, morphology, contact area, and hygroscopicity (9,10). In particular, it has been shown that the surface roughness of the carrier particles has a significant impact on the adhesion and friction forces between the carrier and drug particles (11,12). Adhesion, blend homogeneity, and stability have been directly related to the surface roughness of the carrier particle (13). The ultimate performance properties of DPI blends as determined by in vitro testing has also been correlated to the primary particle surface roughness (13–15). There is an important balance between the relative scaling in the roughness of the particles and the relative size of the carrier and drug particles when considering the effects of surface roughness on particle–particle adhesion. This was previously described (16) and is illustrated by the schematic in Fig. 1. Assuming no other changes in particle properties (i.e., surface energy, particle size, amorphous content, hygroscopicity, etc.), the rank order of drug-carrier adhesion would obey the following trend in roughness of the larger carrier particle: macro-rough surface (Fig. 1a) > smooth surface (Fig. 1b) > micro-rough surface (Fig. 1c). This trend is strictly dependent on the contact area between drug and carrier. If adhesion is too weak, the active drug may be released during inhalation before the particles reach the deep lung. On the contrary, if adhesion is too strong, the active may not be released at all. This phenomenon has been observed and described in detail for several DPI studies (15–19). Fig. 1 Illustration of macro-roughness (a), smooth surface (b), and micro-roughness (c) affects on particle–particle contact and adhesion In this study, we focus on the measurement of micro-scale roughness using fractal dimensions determined from sorption isotherms with different adsorbates.