Design and Evaluation of Hydrophilic Matrix System Containing Polyethylene Oxides for the Zero-Order Controlled Delivery of Water-Insoluble Drugs

Abstract

Abstract. The aim of this study was to design a polyethylene oxide (PEO) binary hydrophilic matrix controlled system and investigate the most important influence(s) on the in vitro water-insoluble drug release behavior of this controlled system. Direct-compressed PEO binary matrix tablets were obtained from a variety of low viscosity hydrophilic materials as a sustained agent, using anhydrous drugs as a model drug. Water uptake rate, swelling rate, and erosion rate of matrices were investigated for the evaluation of the PEO hydrophilic matrix systems. The effect of the dose, the solubility of water-insoluble drug, and the rheology of polymers on in vitro release were also discussed. Based on the in vitro release kinetics study, three optimized PEO binary matrices were selected for further research. And, these PEO binary matrices had shown the similar release behavior that had been evaluated by the similarity factor f 2 . Further study indicated that they had identical hydration, swelling, and erosion rate. Moreover, rheology study exhibited the similar rheological equation of Herschel-Bulkley and their viscosity was also within the same magnitude. Therefore, viscosity plays the most important role to control drug release compared to other factors in PEO binary matrix system. This research provides fundamental understanding of in vitro drug release of PEO binary hydrophilic matrix tablets and helps pharmaceutical workers to develop a hydrophilic controlled system, which will effectively shorten the process of formulation development by reducing trial-and-error.

Polyethylene oxide matrix tablet swelling evolution: The impact of molecular mass and tablet composition

“…If the percolation threshold is not reached, the drug release from such PRTs can be uncontrolled and quite variable. Moreover, the outcome from dissolution results strengthens the research data that the gel layer robustness can be increased with a higher polymer proportion, resulting in a more uniform gel layer and a better-controlled drug release (3,43,48).…”

“…3b), confirming again that with increased M r the gel layer consistency also increases due to a tighter connection between polymer chains. When only PEG was added to polymer (TF 4), the erosion process at a higher flow rate started 3 h later than in TF 6, confirming that other hydrophilic excipients (43) and the drug itself (44) also enhanced hydration of the matrix system. It is interesting to note that the swelling rate is the same for all formulations with added PEG or other excipients (TFs 4-7), but erosion is different and consequently, the tablet degradation depends on PEO's M r (Fig.…”

Redispersible Spray-Dried Powder Containing Nanoencapsulated Curcumin: the Drying Process Does Not Affect Neuroprotection In vitro

“…Additionally, the controlled release profiles showed by LNC-C and SD-LNC-C followed the zero-order kinetics, showing that both are able to provide a constant and sustained drug release, which is highly desirable. These systems spark great interest in the development of pharmaceutical forms, because they would release a drug at a predetermined rate for a specified period of time (40)(41)(42). However, a slight increase in the apparent release constant was calculated for SD-LNC-C, compared with the value obtained for LNC-C, showing that a slight rearrangement in the drug distribution in the particle may occur during the process used to convert the liquid suspension to the powder.…”

Injection moulded controlled release amorphous solid dispersions: Synchronized drug and polymer release for robust performance

“…Upon an increase of stirring rate from 50 to 100 rpm a decrease of the time to 50% released is observed (from approximately 2.9 h to 2.4 h giving a T 50 ratio of approximately 1.2). The data indicates that the release of poorly soluble drugs formulated as a controlled release amorphous solid dispersion using injection moulding has a release less susceptible to variation in hydrodynamics than ER matrix compositions of poorly soluble drugs made using conventional manufacturing methods with similar polymers including dry powder mixing or granulation before final tabletting (Abrahmsén-Alami et al, 2007;Körner et al, 2005;Wang et al, 2017). However, further studies including direct comparisons would be needed to understand the difference in performance in detail.…”