PhD Scientific Days 2024

Poster Session R - Pharmaceutical Sciences and Health Technologies 2.

Studying the effects of commonly used pharmaceutical excipients on permeability and solubility

Text of the abstract

Oral drug delivery is the most common way of drug administration, therefore the examination of the absorption of active substances (APIs) from the gastrointestinal (GI) system is important. The permeability of the molecules can be influenced by many factors, like the physicochemical properties of the API or the other excipients which are part of the formulation. One of the aims of our current study is to investigate the effect of various excipients used commonly in tablets on GI permeability. For the in vitro testing Paralell Artificial Membrane Permeability Assay (PAMPA) measurements were performed. This method is suitable for modeling passive diffusion in a 96-well plate system. Naproxen and pimobendan were used as model compounds. The excipients were used in 3 different concentrations (1:0,5; 1.:1 and 1:3 mass ratio) and the measurements were performed at 3 different pH values (pH=3; 5 and 6,5). To model the GI membrane 4 μl of GIT lipid was used on the surface of a PVDF membrane. The time of the measurement depends on the API and all wells were stirred at 60 rpm. Using these parameters the detection of both the donor and the acceptor sides was possible. To check the suitability of the system, samples without excipients were tested in all cases as a reference. The permeability value was calculated using the PAMPA Explorer software. To investigate the effect of the same excipients on the equilibrium solubility of naproxen and pimobendan, solubility measurements were also carried out using the traditional shake-flask method. In this process, a solution – the same buffers were used as in case of PAMPA measurements – containing the appropriate concentration of excipients was added to the excess solid material. This susepension was stirred for 6 hours, followed by 18 hours of sedimentation. The concentration was determined by UV spectrophotometry. Based on the results of the solubility and permeability measurements, our aim was to investigate the effect of the different concentrations of the excipients on these two important physicochemical parameters, and to select the appropriate excipient concentration in case of naproxen and pimobendan.