Multiple-unit formulation for pulsatile and colon delivery : preparation and in vitro characterization

Purpose: to apply previously identified film-forming formulations of poly(ethyl acrylate, methyl methacrylate) (Eudragit®NE) and the superdisintegrant sodium starch glycolate (Explotab®V17, 15 or 20% on dry Eudragit®NE) to a swellable/erodible oral pulsatile/colon delivery system in order to improve the efficiency of its hydroxypropyl methylcellulose (HPMC) layer in delaying the onset of release, thus allowing the relevant thickness to be reduced to values possibly consistent with size requirements of multiple-unit dosage forms. Methods: an acetaminophen (80%)-containing powder mixture was compacted in a rotary machine (Officine Ronchi, I) equipped with concave punches (2.5mm diameter, 2mm curvature radius). Mini-tablets were coated in fluid bed equipped with rotor insert (GPCG1.1, Glatt, D) with an HPMC (Methocel®E50) aqueous solution up to ~250μm thickness and, subsequently, in bottom-spray fluid bed with the Eudragit®NE30D/Explotab®V17 aqueous dispersions up to ~10, 20 and 30μm thickness. Curing was carried out at 40°C for 24h. In vitro release was tested by disintegration apparatus (800ml of deionized water, 37±1°C, 31 cycles/min, UV analysis, λ=248nm, n=3). Progressive changes in the diameter of coated systems immersed in deionized water were measured on digital photographs (oscillating bath, 37±1°C, 100rpm, n=3). Results: release results showed that both formulations could extend the lag phase imparted by HPMC as such, their effect being dependent on the coating level. Longer lag times and a marked variability were observed in the case of systems provided with the Eudragit®NE film containing 15% of Explotab®V17. Because of a lower hydrophilicity, this film would probably exert a greater impact on HPMC swelling/erosion. Indeed, the morphological changes undergone by the systems when immersed in water showed that the HPMC layer kept swelling even after disruption of such a coat, which was thus hypothesized to hinder a full polymer hydration. By contrast, the film formulation containing 20% of superdisintegrant seemed to slow down the hydration of HPMC but did not limit the extent of its swelling. Conclusions: the Eudragit®NE with 20% Explotab®V17 film formulation was thus proven effective in enhancing the efficiency of the HPMC coat in a multiple-unit swellable/erodible device for oral pulsatile/colon delivery without altering the inherent release controlling mechanism.