Abstract
PolyoxTM coagulant (molecular weight 5 × 106 Da) and hydroxypropyl methylcellulose (HPMC) K4M (USP substitution type 2208) were used to identify the composition variables that ensure the production of polyethylene oxide (PEO) matrix tablets with the same dissolution characteristics as those containing HPMC. Based on the dissolution results obtained using Apparatus 3, a 53% concentration of PEO polymer in the matrix tablet generates comparable drug release as matrix tablets containing 37% HPMC. During the dissolution test, several conditions simulating mechanical stresses in the gastrointestinal tract were investigated, in order to assess the robustness of the gel layer formed in selected PEO and HPMC matrix tablets. Increased mechanical stresses enhanced gel erosion from both matrix tablets evaluated and increased the drug release rate by approximately 10% regardless of the polymer type used. The HPMC gel layer formed was more resilient to mechanical stress and resulted in significantly slower drug release when compared to PEO matrix tablets with the same polymer concentration (37%). The research showed that gel robustness and the PEO polymer percolation threshold are dependent on the mechanical stresses applied. The percolation threshold changed from 30 to 37% when different mechanical stress was applied on Apparatus 2 and 3, respectively. The study revealed that the selection of in vitro dissolution method as well as polymer concentration is important for the evaluation of gel mechanical robustness. Key words: Polyethylene oxide (PEO), hydroxypropyl methylcellulose (HPMC), drug release, percolation threshold, matrix tablets.  
Highlights
Matrix systems are generally designed with a drug, standard tableting excipients, and the most important ingredient: water-swellable polymers
The hydroxypropyl methylcellulose (HPMC) gel layer formed was more resilient to mechanical stress and resulted in significantly slower drug release when compared to polyethylene oxide (PEO) matrix tablets with the same polymer concentration (37%)
The percolation threshold of the selected PEO coagulant (Mw = 5 × 106 Da) was set at 30% with the dissolution test using United States Pharmacopoeia (USP) Apparatus 2 and at 37% when USP Apparatus 3 is used. the study demonstrated the possibility of formulating PEO matrix tablets having a similar drug release rate and robustness as HPMC matrix tablets containing 37% polymer
Summary
Matrix systems are generally designed with a drug, standard tableting excipients, and the most important ingredient: water-swellable polymers. The solid phase transition depends on the degree of crystallinity, which is connected to solvent transport into the solid phase and crystallite unfolding (Trotzig et al, 2007). It is hydrophilic, HPMC is an ion-sensitive polymer, whereas PEO is unsusceptible to ionic strength and pH. With increasing PEO content in the matrix tablet, it is possible to improve its gel strength and simulate HPMC gel behavior. With increased polymer concentration and its viscosity, the drug release mechanism can be changed from mainly erosiondependent to diffusion-dependent (Maggi et al, 2002; Tajiri et al, 2010; Katakam et al, 2013; Hu et al, 2017, Wen et al, 2018)
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