Comparison of film-coated retarded release pellets manufactured by layering technique or by bed rotor pelletization

Abstract

In order to investigate the influence of coatings for controlled active pharmaceutical ingredient (API) release, two types of pellets were used. Microcrystalline pellets were coated with a model API using the Wurster fluidized bed technique in laboratory scale (layered Cellets). Another type of pellets consisting of microcrystalline cellulose and model API was manufactured by fluidized bed rotor pelletization (matrix pellets (MP)). Both kinds of pellets were coated in a Wurster fluidized bed process with a polymer mixture of ethylcellulose to achieve retarded API release. With layered Cellets and an increased thickness of the ethylcellulose layer, the lag-time was increased and the release rate was decreased. In the case of MP, retardation was less pronounced probable due to inhomogeneous polymer film formation as a result of the porous particle surface. To reduce the surface roughness, the MP were coated with polyvinylpyrrolidone (PVP) as an intermediate smoothing layer, in a first trial step by step. In a second trial, pelletization and the coating steps were performed in an uninterrupted process. Intermediate PVP coating improved the ethylcellulose film formation and led to a more pronounced retardation of API release. The uninterrupted process of matrix pellet manufacturing and coating results in a product with only low retarded release.

Premium ethylcellulose polymer based architectures at work in drug delivery

“…Another study further supports this finding as an ethylcellulose film layer/coating over the pellet formulation (Fig. 5(d)) slowed down drug release rate while an increase in the thickness of this layer increased the lag time even more (Priese et al, 2015). It was noted that the surfaces of the pellets were rough and polyvinylpyrrolidone was used as a co-excipient to reduce pellet surface roughness.…”

“…Ethylcellulose aqueous dispersion NF (Aquacoat®) was employed as an external coat layer and it was discovered that amongst other applied excipients layers, it was dominant for exhibited sustained release characteristics, minimized potential effects of pellet core type and nature of the surrounding bulk fluid.

Fig. 5(a) Morphological differences exhibited by Ethocel™ based (a) ofloxacin-loaded floating bioadhesive multiparticulate delivery system (adapted from Zhang et al, 2016a, Zhang et al, 2016b), (b) multi-layered pellets (adapted from Muschert et al, 2009), (c) tacrolimus containing extended release granules (adapted from Tsunashima et al, 2016), (d) rough surfaced pellets (adapted from Priese et al, 2015), (e) osmotic theophylline pellets (adapted from Kazlauske et al, 2017), (f) reservoir type extended release multiparticulates (adapted from Franc et al, 2016), (g) wax based floating sustained-release dispersion pellets (adapted from Yan et al, 2016).

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In-line particle size measurement and agglomeration detection of pellet fluidized bed coating by Spatial Filter Velocimetry

“…The process parameters (Table 2) were selected on the base of experiences from coating processes with Cellets® [19,20] to simulate real conditions and kept constant at the trials.…”

“…In the second part of the project, pellets were coated with a model drug substance according to earlier investigations [19,20] under optimized conditions without any risk of agglomerate formation as well as under worst case process conditions generated by too high spray rate and too low process air temperature to cause agglomeration of the pellets. The aim was the reliable detection of the presence of agglomerates and fines beside the coating product.…”

Formulation development and evaluation of colon targeted delayed release methotrexate pellets for the treatment of colonic carcinoma

“…The excipients were selected based on the literature review (Sogali, Yousuff, Nayak, 2012;Vervaet, Baert, Remon, 1995;Steckel, Mindermann-Nogly, 2004;Priese, Frisch, Wolf, 2015). Pectin, carrargenen, chitosan, ethyl cellulose as release retardants and microcrystalline cellulose (MCC) (Avicel PH 101) as the spheronizing aid were selected for the preformulation studies.…”