In vitro and in vivo evaluation of controlled-release matrix tablets of highly water-soluble drug applying different mw polyethylene oxides (PEO) as retardants

Abstract

The aim of the work presented is to prepare a controlled-release hydrophilic matrix tablet (CMT) controlling release of highly water-soluble drug applying pure combination of high- and low-Mw PEO as matrix materials, to avoid the lag time of drug release, and to overcome incomplete release in later stages. The influences of types and amounts of different Mw PEOs used, drug loading, pH of release medium and agitation rate on drug release were evaluated. The study of uptake and erosion of matrix was conducted and mechanism of improving drug release was discussed. In vivo pharmacokinetics of the CMT and reference preparation self-made controlled-release osmotic pump tablets (COPT) were performed in beagle dogs. The optimized formulation containing 43% PEO WSR 303 and 32% PEO N750 showed a zero order release from 1 h to 12 h. In vivo results demonstrated that the CMT had similar AUC and C with the COPT but smaller T than the COPT and provided a more stable therapeutic concentration compared to the COPT. In conclusion, hydrophilic matrix tablet combining only different Mw PEOs as matrix materials had very good potential to be developed into a controlled-release drug delivery system for highly water-soluble drug. Besides, its manufacturing processes were succinct which would be preferable for modern medicine industry.

Development, optimization and pharmacokinetic evaluation of biphasic extended-release osmotic drug delivery system of trospium chloride for promising application in treatment of overactive bladder

“…None of the batches followed the Higuchi model for release kinetics. Hixon-Crowell release kinetics was shown by TSP-5, TSP-18, and TSP-20 with R 2 between 0.966 and 0.989 [34]. In a factorial design, the TSP-18 was found to be an optimized batch from Design Expert analysis.…”

Novel Aggregation-Induced Emission Fluorescent Molecule for Platinum(IV) Ion-Selective Recognition and Imaging of Controlled Release in Cells

“…By measuring the average diameter by dynamic light scattering of Pdots with 5% PEO- b -PS, the particle size of Pdots increased significantly with time due to swelling of PEO- b -PS, as shown in Figure S20. The gel layer formed by hydration has a greater degree of swelling over time, prolongs the water diffusion path, makes erosion difficult, and delays water getting into Pdots, so it has better sustained release capability. − Therefore, CHTPA–Pt­(IV) complexes can be effectively encapsulated into Pdots with 5% PEO- b -PS, and the controlled release of platinum ions can be achieved in cells. Meanwhile, the AIE fluorescence of CHTPA is also used to provide the monitor signal of platinum ion release in cells (Scheme B).…”

Formulation and Preparation of Losartan-Potassium-Loaded Controlled-Release Matrices Using Ethocel Grade 10 to Establish a Correlation between In Vitro and In Vivo Results

“…Plasma–time curves were also established for the test and formulations. The elimination rate constant (kel) was used to estimate the fractions of the absorbed and unabsorbed drug with the Wagner–Nelson method, as specified in PK-Fit version 2.01 [ 44 ]. The percentage of the drug absorbed was calculated using Equation (11): Percent Absorbed = {(C( t )/Ke + AUC ( o-t )/AUC ( o-∞ )} × 100 …”