Analyzing parametric influences driving age-associated changes in absorption using a PBPK-GSA approach.

The advanced age population may be susceptible to an increased risk of adverse effects due to increased drug exposure after oral dosing. Factors such as high-interindividual variability and lack of data has led to poor characterization of absorption's role in pharmacokinetic changes in this population. Physiologically based pharmacokinetic (PBPK) models are increasingly being used during the drug development process, as their unique qualities are advantageous in atypical scenarios such as drug-drug interactions or special populations such as older people.

The effect of buffer species on biorelevant dissolution and precipitation assays - Comparison of phosphate and bicarbonate buffer.

Biorelevant solubility and dissolution testing is an important tool during pharmaceutical development, however, solubility experiments performed using biorelevant media often do not properly match the solubility data observed in human intestinal fluids. Even though the bicarbonate buffer is the predominant buffer system in the small intestine, in vitro assays are commonly performed using non-volatile buffer systems like phosphate and maleate. In the current study, bicarbonate- and phosphate-buffered biorelevant media were applied to solubility, dissolution, and precipitation testing for a broad range of model compounds.

Increasing the Robustness of Biopharmaceutical Precipitation Assays - Part I: Derivative UV Spectrophotometric Method Development for in-line Measurements.

In vitro precipitation assays are often applied to support drug and formulation development. Current methods applied to quantify the amount of dissolved drug, in particular (U)HPLC, require time-consuming sample preparation. Furthermore, small precipitates formed during the nucleation phase may not be removed quantitatively by filtration or centrifugation of the sample.

Increasing the Robustness of Biopharmaceutical Precipitation Assays - Part II: Recommendations on the use of FaSSIF.

Biopharmaceutical precipitation assays are an important in vitro tool to characterize the precipitation behavior of weakly basic drugs during their transit from the stomach into the small intestine. To mimic the intestinal fluids more closely, biorelevant media like Fasted State Simulated Intestinal Fluid (FaSSIF) and versions thereof are often applied. When applying UV analytics to measure the drug concentration during the transfer experiments, changes in the UV spectrum of the medium have been observed when FaSSIF was stored over a longer period of time or under accelerated conditions.

Sustained-release hot melt extrudates of the weak acid TMP-001: A case study using PBB modelling.

Over the last 30 years, hot melt extrusion has become a leading technology in the manufacture of amorphous drug delivery systems. Mostly applied as an 'enabling formulation' for poorly soluble compounds, application in the design of sustained-release formulations increasingly attracts the attention of the pharmaceutical industry. The drug candidate TMP-001 is currently under evaluation for the early treatment of Multiple Sclerosis.

Predicting the environmental emissions arising from conventional and nanotechnology-related pharmaceutical drug products.

Today, environmental pollution with pharmaceutical drugs and their metabolites poses a major threat to the aquatic ecosystems. Active substances such as fenofibrate, are processed to pharmaceutical drug formulations before they are degraded by the human body and released into the wastewater. Compared to the conventional product Lipidil® 200, the pharmaceutical product Lipidil 145 One® and Ecocaps take advantage of nanotechnology to improve uptake and bioavailability of the drug in humans.