Pharmaceutical Technology Division

COMPRESSION BEHAVIOUR AND ENTERIC FILM COATING PROPERTIES OF CELLULOSE ESTERS Guo, H. X., 2002, Dissertations Biocentri Viikki Universitatis Helsingiensis 19/2002 pp. 40 ISBN 952-10-0653-6 (print), ISBN 952-10-0654-4 (pdf), ISSN 1239-9469 The main purpose of this study was to investigate the phenomena related to the compression behaviour and enteric film coating properties of pharmaceutical cellulose esters. The particle deformation in the tablet compression and drug diffusion of film-coated pellets were studied using non-invasive confocal laser scanning microscopy (CLSM). Autofluorescent riboflavin sodium phosphate (RSP) was used as a model drug for preparing tablets and pellets. Tablets of 1% RSP with two grades of microcrystalline cellulose (MCC) were individually compressed at compression forces of 1.0 kN and 26.8 kN. The matrices were made by direct compression of mixtures of two established enteric cellulose esters, i.e. cellulose acetate phthalate (CAP) and hydroxypropyl methylcellulose acetate succinate (HPMCAS), and MCC. Pellets were made with the extrusion/spheronisation technique. The pellets were film-coated by the air-suspension method with an aqueous dispersion of CAP. The results suggested that the compression behaviour of both the autofluorescent drug RSP and the non-fluorescent filler MCC can be visualised simultaneously by using fluorescence and reflection modes in CLSM. RSP particles partly dissolved under compression and then recrystallised. In studying the compression of matrix tablets confocal images confirmed the Heckel plot results. CLSM micrographs of the surface of the tablets made from CAP and MCC (1:1) showed more deformation than the one from HPMCAS and MCC (1:1). Slight aggregation of HPMCAS particles may influence their deformation. There were larger voids in the tablets made from cellulose ester and MCC (1:3) mass than in the one made from cellulose ester and MCC (1:1) mass. A well-behaving enteric film-coating formulation was developed and patented. The coating formulation was based on waxy maize starch (amylopectin) as a co-filler in the pellet cores, and this innovation evidently prevented the premature drug migration from the core into the film coat layer. Confocal images of film-coated pellets at 30% theoretical weight increase showed that the amylopectin-containing pellets had a more appreciable coalescence of the polymer spheres than the respective lactose-containing pellets. The dissolution test was consistent with the confocal microscopy results. Amylopectin as subcoating material can prevent the influx of the dissolution medium into the pellet core, and thus decrease the premature dissolution and release of the drug from the enteric-coated pellets in 0.1 N HCl solution. The drug release mechanism appeared to be osmotically driven release, followed by diffusion through the polymer film. Therefore, particle deformation in the tablet compression, drug migration of enteric-coated pellets and release mechanism can be studied using a non-invasive CLSM technique.