Forecasting the effect of water gastric emptying patterns on model drug release in an in vitro glass-bead flow-through system.

Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its emptying kinetics. The purpose of this study was thus to simulate different individual water gastric emptying (GE) patterns in an in vitro glass-bead flow-through dissolution system. Further, the effect of GE on the dissolution of model drugs from immediate-release tablets was assessed by determining the amount of dissolved drug in the samples pumped out of the stomach compartment. Additionally, different HCl solutions were used as dissolution media to assess the effect of the variability of pH of the gastric fluid on the dissolution of three model drugs: paracetamol, diclofenac sodium, and dipyridamole. The difference in fast and slow GE kinetics resulted in different dissolution profiles of paracetamol in all studied media. For diclofenac sodium and dipyridamole tablets, the effect of GE kinetics was well observed only in media, where the solubility was not a limiting factor. Therefore, GE kinetics of co-ingested water influences the drug release from immediate-release tablets, however, in certain cases, other parameters influencing drug dissolution can partly or fully hinder the expression of this effect.

Formulation and Characterization of Buccal Films Containing Valsartan with Additional Support from Image Analysis.

The present study was aimed to the development and characterization of valsartan-containing buccal films with an introduction to a novel technique of image analysis. Visual inspection of the film provided a wealth of information that was difficult to quantify objectively. The obtained images of the films observed under the microscope were embedded in a convolutional neural network (CNN). The results were clustered according to their visual quality and on the basis of data distances. Image analysis proved to be a promising method to characterize buccal films appearance and their visual properties. The differential behavior of film composition was investigated using a reduced combinatorial experimental design. Formulation properties such as dissolution rate, moisture content, valsartan particle size distribution, film thickness, and drug assay were evaluated. In addition, more advanced methods such as Raman microscopy and image analysis were used to characterize the developed product in more detail. The results of dissolution tests using four different dissolution apparatuses showed a significant difference between the formulations containing the active ingredient in different polymorphic states. The dynamic contact angle of a water droplet on the surface of the films was measured, which correlated well with the dissolution times at 80% of the released drug (t80).

The Influence of Simulated Fasted Gastrointestinal pH Profiles on Diclofenac Sodium Dissolution in a Glass-Bead Flow-Through System.

High inter- and intra-individual variability in the pH of fluids in the human gastrointestinal (GI) tract has been described in the literature. The aim of this study was to assess the influence of physiological variability in fasted pH profiles of media along the GI tract on diclofenac sodium (DF-Na) dissolution from matrix tablets. Four individual in vivo fasted pH profiles were selected from the literature that differed in pH values and transit times from the stomach to the proximal colon. Using a glass-bead device flow-through dissolution system, these pH profiles were simulated in vitro using a specific media sequence and considering simulated intestinal buffer capacities corresponding to in vivo literature data. Dissolution experiments were then performed in the same system with media sequence following individual pH profiles. In dissolution experiments, where influences of simulated gastric emptying time (GET), gastric pH value, small intestinal transit time, and colonic pH were studied; high influence of gastric pH value and GET on DF-Na dissolution was observed. The effect of variability in pH profiles in the range of individual in vivo data on DF-Na dissolution was also clearly observed in experiments, where dissolution studies were performed following three simulated in vivo individual pH profiles. The differences in DF-Na release between three individual pH profiles were substantial; they also reflected in simulated plasma concentration profiles and can be attributed to pH dependent diclofenac solubility.