Biomedical subjects

Barbara Lueckel

Publications and source records attributed to Barbara Lueckel.

2 recordsLinked to original sources

PubMed2006

Strategies for the design of hydrophilic matrix tablets with controlled microenvironmental pH.

Incorporation of weak acids as pH modifiers enhances the release of weakly basic drugs in higher pH environments by reducing the microenvironmental pH (pHM). The objectives of this study were: (a) to investigate the relationship between pHM, drug release, and pH modifier release and (b) to achieve simultaneous release of the drug and the pH modifier over the entire dissolution time (6 h, phosphate buffer, pH 6.8). Using dipyridamole as a model drug, we investigated drug and acid release and determined the average pHM potentiometrically using tablet cryosections. The first approach was based on incorporating different concentrations of pH modifiers in conventional matrix tablets based on hydroxypropylmethylcellulose. Owing to its high acidic strength and low aqueous solubility, fumaric acid resulted in simultaneous release and maintained a constant acidic pHM. Secondly, press-coated matrix tablets, comprising an acidic reservoir, were found to be a valuable approach for retarding the diffusion of more water-soluble acids. Using the power law expression (Mt/Minfinity = ktn) it became evident that the inclusion of acids increased drug release. Higher acid concentrations tended to decrease n standing for the slope, whereas the release constant k increased. Furthermore, the medial check term parameters depended on the type of pH modifier used.

Drug Design↗

PubMed2006

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

Incorporation of pH modifiers is a commonly used strategy to enhance the dissolution rate of weakly basic drugs from sustained release solid dosage forms. Electron paramagnetic resonance imaging (EPRI) was applied to spatially monitor pH(M) and the rotational correlation time (tau(R)), a parameter which is closely related to the surrounding microviscosity inside HPMC (hydroxypropylmethylcellulose) matrix tablets. Fumaric, citric, and succinic acid were employed as pH modifiers. 4-(methylamino)-2-ethyl-5,5-dimethyl-4-pyridine-2-yl-2,5-dihydro-1H-imidazole-1-oxyl (MEP) was used as spin label. Fumaric and citric acid reduced the pH(M) to equal extents in the initial phase. With the progress of hydration, the more soluble citric acid diffused out from the tablet resulting in an increase in pH(M), originating at the outer layers. In contrast, fumaric acid maintained a constantly reduced pH(M) inside the entire tablet. Due to its lower acidic strength, succinic acid did not reduce the pH(M) as effectively as the other pH modifiers used. The more water-soluble acids stimulated the water penetration into the matrix system, thereby rapidly decreasing tau(R). Once the matrix tablets were hydrated, the included pH modifiers influenced tau(R) insignificantly. EPRI, a novel approach for monitoring pH(M) and tau(R) non-invasively and spatially resolved, was used successfully for the optimization of an pH-controlled formulation.

Chemistry, Pharmaceutical↗