Microenvironmental pH and microviscosity inside pH-controlled matrix tablets: An EPR imaging study

Release Characteristics of Quetiapine Fumarate Extended Release Tablets Under Biorelevant Stress Test Conditions

“…This was probably the reason for higher dissolution rates observed in our experiments. The dissolution profiles of 400-mg tablets were less influenced by environmental pH under both stress and standard test conditions which may be related to the relatively slower water uptake than in the case of 50-mg tablets (22)(23)(24).…”

Microenvironmental pH Control and Mixed Polymer Approaches to Optimise Drug Delivery with Hydrophilic Matrix Tablets

“…EPR imaging has been applied in the context of tracking microenvironmental pH and to spatially monitor pH and the rotational correlation time, tau(R), a parameter indicative of the surrounding microviscosity within HPMC matrix tablets [40]. In the study, fumaric, citric and succinic acids were employed as pH modifiers in a matrix tablet, with 4-(methylamino)-2-ethyl-5,5-dimethyl-4-pyridine-2-yi-2,5-dihydro-1H-imidazole-1-oxyl (MEP) as the spin label.…”

“…EPR could provide information on both the spatial distribution and the evolution of pH within an individual hydrating tablet, providing a data over the entire course of hydration [41]. The only disadvantage of EPR studies is that the pH range that can be studied is in a narrow window, around ±1.0 to 1.5 pH units of the pK a of the spin probe [40,41]. If a wider range of pH would need to be measured, this would require running parallel studies with other spin probes with different pK a s.…”

“…There must be sufficient reserve in the matrix to sustain the lowered pH, as of course not only will the now more soluble ionised form of the basic drug readily diffuse from the hydrated matrix, but the organic acid modifier will also be released. Siepe et al [40] investigated the relationship between the microenvironmental pH, drug release and pH modifier release. They sought to achieve simultaneous release of both the drug and the pH modifier over the entire 6 h dissolution time in phosphate buffer (pH 6.8).…”

“…Although citric acid has been shown to be liberated more rapidly than fumaric acid from hydrophilic matrix tablets during in vitro release studies [40] again associated with its solubility properties, it has been successfully employed to modulate the in vitro release of several basic drugs [45][46][47][48][49]. These studies allowed some characterisation of the impact of the acidifier on the drug release mechanism.…”