Evaluation of silicone elastomers for tablet coating.

摘要

The objective of this project was to study the effect of modifications of endhydroxylated poly(dimethylsiloxane) (PDMS) formulations on tablet drug release. Emulsions of crosslinked endhydroxylated PDMS, a novel film-forming polymer, were characterized and investigated for their ability to be applied onto tablet cores in a spray-coating process for controlled drug release.; Modifications of the crosslinking agent from the most commonly used tetraethylorthosilicate (TEOS) to the trifunctional 3-(2,3-epoxypropoxy)propyltrimethoxysilane (SIG) and a 1:1-mixture of the two crosslinker were undertaken.; Addition of vermiculate clay, copolymeric substances and different channeling-agents were studied. Copolymers of methylpolysiloxane with polyoxyethylene (DC193 and DC5324) or dimethyl,methyl (polyoxyethylene) (DCQ2-5220) as well as poly (acrylamide-co-acrylic acid) were used. Lactose, microcrystalline cellulose (MCC) and polyethyleneglycol 8000 (PEG) were the channeling-agents applied.; A change in molecular weight of the PDMS was analyzed.; Effects on dispersion properties were characterized by particle size distribution, viscosity and visual observation of phase-separation. Mechanical properties of resulting cast and sprayed films were studied to determine applicability in a pan-coating process. Release of Hydrochlorothiazide (marker-drug) was studied from tablets coated in a lab-size conventional coating pan.; Dispersions were found suitable for a spray-coating process. Only the formulation with acrylic-copolymer addition was unstable as phase separation occurred.; Preparation of free films showed that methylpolysiloxane-copolymers negatively affected the mechanical properties so that coating onto tablet cores was not possible.; Tablets coated with formulations crosslinked using the 1:1-mixture of SIG/TEOS and containing polyethyleneglycol were most suitable to control drug release, at 5% coating weight. Constant release rates were achieved for formulations with up to 25% (w/w of PDMS) PEG; higher amounts resulted in a non-linear release pattern. Upon adding 50% PEG, a drug release of 62% over 24 hours could be achieved.; Formulations containing 25 and 50% (w/w of PDMS) PEG were stable for at least 3 months when tested according to ICH-guidelines.; In comparison with Eudragit NE (copolymeric product of 2:1 ethylacrylate/methylmethacrylate) PDMS-formulations showed similar mechanical and improved spray-application properties. Addition of channeling agents was necessary for both products to achieve drug release. The effect of polyethyleneglycol was greater on formulations based on PDMS than for Eudragit NE.