PENGARUH VARIASI pH DAPAR FOSFAT TERHADAP PROFIL ABSORPSI PARASETAMOL MENGGUNAKAN MODEL EVERTED SAC DUODENUM KELINCI SECARA EKS VIVO

Authors

  • Gratia Apulina Cindylawsa Purba Fakultas Farmasi, Institut Kesehatan Deli Husada Deli Tua
  • Putri Anggita Fakultas Farmasi, Institut Kesehatan Deli Husada Deli Tua
  • Delisma Marsauli Simorangkir Fakultas Farmasi, Institut Kesehatan Deli Husada Deli Tua
  • Ageng Azhar Amar Fakultas Farmasi, Institut Kesehatan Deli Husada Deli Tua

DOI:

https://doi.org/10.36656/0rjv0w60

Keywords:

pH, paracetamol, everted sac, duodenum, rabbit

Abstract

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

Downloads

Download data is not yet available.

References

Azman, M., Sabri, A. H., Anjani, Q. K., Mustaffa, M. F., & Hamid, K. A. (2022). Intestinal absorption study: Challenges and absorption enhancement strategies in improving oral drug delivery. Pharmaceuticals, 15(8), 975. https://doi.org/10.3390/ph15080975

Bagnall, W. E. (1979). The gastrointestinal absorption of paracetamol in the rat: In vitro and in vivo studies including everted gut sacs. Diakses dari https://pubmed.ncbi.nlm.nih.gov/34689/

Diningsih, Y., & Hasibuan, E. S. (2023). Analisis kadar parasetamol dalam sediaan tablet dengan menggunakan spektrofotometer UV-Visible. https://ojs.unhaj.ac.id/index.php/fj/article/view/914

Lee, K.J., dkk. (2005). Effect of experimental pH on the in vitro permeability in intact rabbit intestines and Caco-2 monolayer. Eur J Pharm Sci. https://doi.org/10.1016/j.ejps.2005.02.012

Mészáros, P., Kovács, S., Kulcsár, G., Páskuj, M., & Almási, A. (2022). Investigation of intestinal absorption and excretion of paracetamol in streptozotocin-induced hyperglycemia. International Journal of Molecular Sciences, 23(19), 11913. https://doi.org/10.3390/ijms231911913

Morita, T., Yoshida, H., Tomita, N., & Sato, Y. (2025). Pharmaceutical excipients that alter intestinal drug Absorption: A systematic review of Excipient–Drug interactions. Journal of Drug Delivery Science and Technology, 107850. https://doi.org/10.1016/j.jddst.2025.107850

Noorman, L., van der Hee, B., & Gilbert, M. S. (2024). Assessing seromuscular layer and serosa removal on intestinal permeability measurements in weaned piglet everted sac segments. Diakses dari https://pmc.ncbi.nlm.nih.gov/articles/PMC11222984/

Onoue, S., Yamada, K., & Sato, H. (2025). Advanced oral drug delivery systems: Current challenges and emerging technologies. Acta Pharmaceutica Sinica B. https://doi.org/10.1016/j.apsb.2025.11.036

Patil, A., Raheja, V., & Damre, A. (2010). Simultaneous analysis of intestinal permeability markers, caffeine, paracetamol and sulfasalazine by RP-HPLC: Tool for the standardization of rat everted gut sac model. Diakses dari https://www.researchgate.net/publication/215926953

Shi, Q., Carrillo, J.-C., & Michael, G. (2022). Assessment of the intestinal absorption of higher olefins by the everted gut sac model in combination with in silico new approach methodologies. Chemical Research in Toxicology. https://doi.org/10.1021/acs.chemrestox.2c00089

Supiyani, A., Agussetiandari, I., Handayani, T., & Sukmawati, D. (2023). Effects of synbiotic milk on the duodenal mucosa structure of mice induced by high doses of trans oil: Animal research. Health Information: Jurnal Penelitian, 15(1), 23–31.

Wang, R., Kang, Z., Li, M., Zhang, Z., Guo, Y., Niu, S.,& Liu, M. (2025). Effect of luteolin on ceftiofur intestinal absorption: the rational use of Caco-2 monolayer cell model and everted gut sac model. Poultry Science, 104(9), 105409. https://doi.org/10.1016/j.psj.2025.105409

Xie, L., Hong, Y., Hu, Y., Li, H., Lou, J., & Zhou, X. (2025). Prioritizing oral bioavailability in drug development strategies. Future Medicinal Chemistry, 17(2), 149-151. https://doi.org/10.1080/17568919.2024.2444871

Zanuba, A., Permatasari, L., Febrianingsih, K. D., Anindiya, N. W., Razkianita, H., & Mustika, M. J. (2025). Review artikel: validasi metode analisis kadar parasetamol dalam sediaan obat menggunakan berbagai instrumen. Sasambo Journal of Pharmacy, 6(1), 56-61. DOI: 10.29303/sjp.v6i1.502

Downloads

Published

10/31/2026

Most read articles by the same author(s)