<![CDATA[Paracetamol is the most widely used non-opioid analgesic-antipyretic, yet its oral bioavailability (70–90%) is influenced by the physiological conditions of the gastrointestinal tract, including intraluminal pH. This study aimed to analyze the effect of phosphate buffer pH variation (pH 5.8 and 7.4) on the absorption profile of paracetamol using an ex vivo rabbit everted duodenal sac model. Paracetamol concentrations in the serosal fluid were measured serially at 0, 5, 10, 20, 30, 40, 50, and 60 minutes using UV-Vis spectrophotometry at an analytical wavelength of 243 nm. The calibration curve at pH 5.8 yielded the linear regression equation y = 0.108x – 0.009 (r = 0.998), while at pH 7.4 the equation y = 0.045x + 0.019 (r = 0.999) was obtained, indicating high linearity under both conditions. Paracetamol concentration in the serosal compartment increased progressively up to around minutes 20–40 under both pH conditions, with a higher concentration profile observed at pH 7.4 compared to pH 5.8, consistent with the increased non-ionized fraction of paracetamol approaching the physiological duodenal condition. Concentration fluctuations during the final minutes of incubation are presumed to relate to the serial dilution effect from sampling replacement and declining tissue viability over time. This study demonstrates that intraluminal pH plays an important role in determining the rate and extent of paracetamol absorption in the rabbit everted duodenal sac model, providing a basis for the formulation of pH-sensitive oral dosage forms]]>
