PhD Scientific Days 2022

Pharmaceutical Sciences II. (Poster discussion will take place in the Aula during the Coffee Break)

Investigation of Factors Influencing the Solubility and Permeability of Drugs

Text of the abstract

Introduction: Pharmacokinetics are greatly determined by the physico-chemical properties of the drug. Solubility, dissolution and permeability are playing an important role in the absorption of drug molecules. The Biopharmaceutical Classification System also classifies compounds based on their solubility and permeability.
Aims: The aim of this study was to investigate the effect of particle size, different excipients, pH and biomimetic medium on the above mentioned physicochemical properties. Solubility, dissolution, and permeability of niflumic acid were investigated under biorelevant conditions. Measurements were performed with macrocrystalline, micronized, and nanonized forms. For nanonization, two excipients, polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVPK25) were used.
Methods: Measurements were performed in Fasted and Fed State Simulated Intestinal Fluid (FaSSIF and FeSSIF) blank and full buffers. Properties of macrocrystalline and micronized forms were also determined in the presence of excipients (1: 1 ratio, like used in case of nanonization). Equilibrium solubility was measured by the saturated shake flask method, dissolution was monitored in situ with UV probes. Permeability was measured with the µFlux apparatus.
Result: Solubility was the highest in FaSSIF full medium. In blank buffers, nanonization resulted a nearly twofold increase in solubility. PVPK25 increased the solubility more than PVA. A solubilizing effect was observed in the biomimetic medium: the solubility in FeSSIF full was nearly ten times higher than the concentration measured in FeSSIF blank buffer.
The permeability of the macrocrystalline niflumic acid was the highest. Using PVA or PVPK25 as a physical mixture next to the macrocrystalline form resulted a decrease in permeability. The micronized sample showed the same permeability alone and in the presence of excipients.
Conclusion: Reducing particle size can be an effective way to improve solubility. Excipients used for nanonization may have a solubilizing effect in themselves. The solubilizing effect of the biorelevant medium is more pronounced, when some of the molecules are in a non-ionized state at a given pH.