0000000000116981
AUTHOR
Per Holm
IVIVC for fenofibrate immediate release tablets using solubility and permeability as in vitro predictors for pharmacokinetics.
The goal of this study was to investigate the in vitro-in vivo correlation (IVIVC) for fenofibrate immediate release (IR) tablet formulations based on MeltDose-technique. The in vitro determined drug solubility and permeability data were related to the C(max) values observed from two in vivo human studies. Solubility and permeation studies of fenofibrate were conducted in medium simulating the fasted state conditions in the upper jejunum, containing the surfactant compositions of the six formulations at different concentrations. The behavior of all surfactant compositions was characterized by surface tension, dynamic light scattering, and cryo-TEM. The obtained solubility and permeation dat…
Influence of polymer molecular weight on in vitro dissolution behavior and in vivo performance of celecoxib:PVP amorphous solid dispersions
In this study, the influence of the molecular weight of polyvinylpyrrolidone (PVP) on the non-sink in vitro dissolution and in vivo performance of celecoxib (CCX):PVP amorphous solid dispersions were investigated. The dissolution rate of CCX from the amorphous solid dispersions increased with decreasing PVP molecular weight and crystallization inhibition was increased with increasing molecular weight of PVP, but reached a maximum for PVP K30. This suggested that the crystallization inhibition was not proportional with molecular weight of the polymer, but rather there was an optimal molecular weight where the crystallization inhibition was strongest. Consistent with the findings from the non…
Evaluation of drug-polymer solubility curves through formal statistical analysis: comparison of preparation techniques.
ABSTRACT: In this study, the influence of the preparation technique (ball milling, spray drying, and film casting) of a supersaturated amorphous dispersion on the quality of solubility determinations of indomethacin in polyvinylpyrrolidone was investigated by means of statistical analysis. After annealing of the amorphous dispersions above the crystallization temperature for 2 h, the solubility curve was derived from the glass transition temperature of the demixed material using the Gordon–Taylor relationship and fitting with the Flory–Huggins model. The study showed that the predicted solubility from the ball-milled mixtures was not consistent with those from spray drying and film casting,…
Influence of Polymer Molecular Weight on Drug–polymer Solubility: A Comparison between Experimentally Determined Solubility in PVP and Prediction Derived from Solubility in Monomer
ABSTRACT: In this study, the influence of polymer molecular weight on drug–polymer solubility was investigated using binary systems containing indomethacin (IMC) and polyvinylpyrrolidone (PVP) of different molecular weights. The experimental solubility in PVP, measured using a differential scanning calorimetry annealing method, was compared with the solubility calculated from the solubility of the drug in the liquid analogue N-vinylpyrrolidone (NVP). The experimental solubility of IMC in the low-molecular-weight PVP K12 was not significantly different from that in the higher molecular weight PVPs (K25, K30, and K90). The calculated solubilities derived from the solubility in NVP (0.31–0.32 …