A multiparticulate dosage form has been formulated to modify the release of acetaminophen (APAP) from ethyl cellulose (EC)-coated pellets. This research work examines the use of hydrophilic excipients in films formed from an aqueous-based EC dispersion devoid of widely used traditional pore formers, i.e., hydroxypropyl methyl cellulose (HPMC) and poly (vinyl alcohol)–poly (ethylene glycol) (PVA–PEG), to develop stable, controlled-release pellets. For this purpose, water-soluble or hydrophilic additives, namely triethyl citrate (TEC) and triacetin, were used to modify/control the release of the APAP from EC-based coated pellets.
As part of the preformulation study, to understand if the given polymer-based coating formulation is acceptable to be applied to the substrate, a polymeric, free-film study was conducted. The polymeric films, cast using five different concentrations of either TEC or triacetin ranging from 0 to 50% w/w, were evaluated for thermal (glass-transition temperature, Tg) mechanical (tensile strength, Young’s modulus, and elongation) and structural properties. The inclusion of the hydrophilic excipients (TEC or triacetin) had a significant effect on the glass transition temperature and thermal properties of the polymeric films. The results showed that the plasticization effect caused by the added excipients reduced the glass-transition temperature (Tg), tensile strength, and Young’s modulus, and increased the percent elongation at rupture of the free polymeric films. In addition, the surface characteristics or morphology of the evaluated films also improved resulting in more homogenous and smoother films at higher excipient concentrations. The effect on the thermal, mechanical, and structural properties of the polymeric films were related to the concentrations and polymer affinity of the excipients. Based on the conclusion from the polymeric free-film study for the pellet coating, the effect of TEC and triacetin on EC based films was examined at concentrations of 20, 30, 40, and 50% w/w. The coating procedure was performed using the Wurster drug-layering process where the solution/suspension of the drug is layered onto the inert sugar spheres followed by the rate controlling polymer layering to obtain the controlled release function. The drug release from the drug layered polymer coated pellets was determined using standard dissolution testing methodology.
The release of APAP was modified with the application of the ethyl cellulose film containing hydrophilic/water-soluble additives (TEC and triacetin) without any traditionally used pore formers (HPMC/PVA-PEG). Among the two excipients evaluated, TEC, due to its higher affinity for the ethyl cellulose polymer, was found to be a highly effective release modifier for aqueous ethyl cellulose-coated pellets. Ethyl cellulose-coated, drug-layered pellets using TEC at 30% w/w concentration resulted in a sustained-release profile similar to using traditional pore formers, such as HPMC, PVA and PEG. In addition, the use of TEC also optimized the current complex manufacturing process by eliminating the time-intensive curing step or thermal treatment which is required when using traditional pore formers.
|School:||University of the Sciences in Philadelphia|
|School Location:||United States -- Pennsylvania|
|Source:||DAI-B 80/09(E), Dissertation Abstracts International|
|Keywords:||Aqueous ethyl cellulose dispersions, Controlled-release pellets, Hydrophilic/water-soluble additives|
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