Dissolution and pharmacokinetics profile of acetylsalicylic acid in rabbit plasma following oral ingestion of acetylsalicylic acid microcapsules

Faizatun; Ni Made Dwi Sandhiutami

doi:10.35814/jifi.v24i1.2092

Penulis

Faizatun Department of Pharmaceutical Technology, Faculty of Pharmacy, Universitas Pancasila, Jakarta, 16420, Indonesia
Ni Made Dwi Sandhiutami Department of Pharmacology, Faculty of Pharmacy, Universitas Pancasila, Jakarta, 16420, Indonesia

DOI:

https://doi.org/10.35814/jifi.v24i1.2092

Kata Kunci:

Acetylsalicylic acid, bioavailability, dissolution, microcapsule, pharmacokinetic

Abstrak

Acetylsalicylic acid (80 mg) suppresses thromboxane A2 (TXA-2) formation, thereby reducing platelet aggregation and is used as an antiplatelet agent. Oral administration of acetylsalicylic acid causes gastrointestinal bleeding; therefore, acetylsalicylic acid microcapsules have been developed, which are less soluble in stomach acid but dissolve in intestinal fluid. This study aimed to evaluate the concentration, dissolution, and bioavailability of acetylsalicylic acid (ASA) microcapsules. Microcapsules were prepared using the microencapsulation method with an alginate crosslinking technique, with calcium chloride as the crosslinker. The concentration of acetylsalicylic acid and the dissolution of microcapsules were determined in vitro. The bioavailability of 80 mg acetylsalicylic acid microcapsules was studied in rabbits that were orally administered of 80 mg. Blood sampling was carried out at 0, 0.5, 1, 2, 4, 6, 8, 8.5, 9, 9.5, 10, 12, 14, 16, 24, and 30 h. In this study, the percentage of acetylsalicylic acid in the microcapsules was 24.08±0.59%. The dissolution test at the acid stage showed that acetylsalicylic acid was still released at 40.09% in 90 min. In the bioavailability test, a lag time of absorption of less than 1 h was obtained, peak plasma levels of 2.06 μg/mL were achieved within 9.16 h after microcapsule administration, and the area under the curve was 15.98 μg · h/mL. It can be concluded that the release of acetylsalicylic acid from microcapsules in the acidic medium indicates incomplete entrapment, and there is a lag time, indicating inhibition of drug release due to the microencapsulation process.

Referensi

[1] K. Khasanah, D. Nawangsari, and I. Y. Kusuma, “Solid Dispersion of acetylsalicylic acid using Polyvinyl Pyrrolidone (PVP) K-30 in tablets with direct compressing method Indo.” J. Chem. Res., vol.10, no.3, pp. 183-94, 2023, doi: 10.30598//ijcr.2023.10-kha

[2] M. Djojosaputro and C. R. L. Aritonang, “Overview of anti-platelet drug use in ıschemic stroke patients at UKI general hospital in 2015,” J. Drug Deliv. Ther., vol. 12, no. 2, pp. 34–39, 2022, doi: http://dx.doi.org/10.22270/jddt.v12i2-s.5262

[3] N. Hadiyanti, D. Hasmono, and M. S. Islam, “Analysis of differences of serum thromboxane B2 level after taking acetosal in acute thrombotic stroke with diabetes mellitus and non-diabetes mellitus,” Folia Medica Indones., vol. 54, no. 1, pp. 53–58, 2018, doi: 10.20473/fmi.v54i1.8053

[4] L. A. Kusumawardani, R. Andrajati, and A. Nusaibah, “Drug-related problems in hypertensive patients: A cross-sectional study from Indonesia,” J. Res. Pharm. Pract., vol. 9, no. 3, pp. 140–145, 2020, doi: 10.4103/jrpp.JRPP_20_16

[5] K. Schrör and M. Voelker, “NSAIDS and aspirin: Recent advances and implications for clinical management,” NSAIDs Aspirin Recent Adv. Implic. Clin. Manag., pp. 107–122, 2016, doi: https://doi.org/10.1007/978-3-319-33889-7_7

[6] B. Driver, D. C. Marks, and D. E. van der Wal, “Not all (N) SAID and done: Effects of nonsteroidal anti-inflammatory drugs and paracetamol intake on platelets,” Res. Pract. Thromb. Haemost., vol. 4, no. 1, pp. 36–45, 2020, doi: https://doi.org/10.1002/rth2.12283

[7] A. P. Jacobsen et al., “Lifelong aspirin for all in the secondary prevention of chronic coronary syndrome: still sacrosanct or is reappraisal warranted?,” Circulation, vol. 142, no. 16, pp. 1579–1590, 2020, doi: DOI: 10.1161/CIRCULATIONAHA.120.045695

[8] V. Sabatini et al., “Design of new polyacrylate microcapsules to modify the water-soluble active substances release,” Polymers (Basel)., vol. 13, no. 5, p. 809, 2021, doi: https://doi.org/10.3390/polym13050809

[9] A. Valdés, M. Ramos, A. Beltran, and M. C. Garrigos, “Recent trends in microencapsulation for smart and active innovative textile products,” Curr. Org. Chem., vol. 22, no. 12, pp. 1237–1248, 2018, doi: https://doi.org/10.2174/1385272822666180430130528

[10] C. Huynh Mai, T. Thanh Diep, T. T. T. Le, and V. Nguyen, “Advances in colloidal dispersions: A review,” J. Dispers. Sci. Technol., vol. 41, no. 4, pp. 479–494, 2020, doi: 10.1080/01932691.2019.1591970

[11] F. Molavi, M. Barzegar-Jalali, and H. Hamishehkar, “Polyester based polymeric nano and microparticles for pharmaceutical purposes: A review on formulation approaches,” J. Control. Release, vol. 320, pp. 265–282, 2020, doi: https://doi.org/10.1016/j.jconrel.2020.01.028

[12] N. M. Sanchez-Ballester, B. Bataille, and I. Soulairol, “Sodium alginate and alginic acid as pharmaceutical excipients for tablet formulation: Structure-function relationship,” Carbohydr. Polym., vol. 270, p. 118399, 2021, doi: https://doi.org/10.1016/j.carbpol.2021.118399

[13] S. Lu, S. Kong, Y. Wang, Z. Hu, L. Zhang, and M. Liao, “Gastric acid-response chitosan/alginate/tilapia collagen peptide composite hydrogel: Protection effects on alcohol-induced gastric mucosal injury,” Carbohydr. Polym., vol. 277, p. 118816, 2022, doi: https://doi.org/10.1016/j.carbpol.2021.118816

[14] T. M. do Prado, F. H. Cincotto, and S. A. S. Machado, “Spectroelectrochemical study of acetylsalicylic acid in neutral medium and its quantification in clinical and environmental samples,” Electrochim. Acta, vol. 233, pp. 105–112, 2017, doi: https://doi.org/10.1016/j.electacta.2017.03.038

[15] M. T. Katona, “In vıtro method developments for the better predıctıon of bıoavaılabılıty,” 2024.

[16] S. Liu, X. Wu, J. Hu, Z. Wu, and Y. Zheng, “Preparation and characterisation of a novel polylactic acid/hydroxyapatite/graphene oxide/aspirin drug-loaded biomimetic composite scaffold,” New J. Chem., vol. 45, no. 24, pp. 10788–10797, 2021, doi: https://doi.org/10.1039/D1NJ01045J

[17] G. Ma and H. Yue, “Advances in uniform polymer microspheres and microcapsules: Preparation and biomedical applications,” Chinese J. Chem., vol. 38, no. 9, pp. 911–923, 2020, doi: https://doi.org/10.1002/cjoc.202000135

[18] M. Stielow, A. Witczyńska, N. Kubryń, Ł. Fijałkowski, J. Nowaczyk, and A. Nowaczyk, “The bioavailability of drugs—the current state of knowledge,” Molecules, vol. 28, no. 24, p. 8038, 2023, doi: https://doi.org/10.3390/mol

[19] F. Lim, Biomedical applications of microencapsulation. CRC press Boca Raton, FL, 2019.

[20] J. Jović et al., “Pharmacokinetic and drug absorption profiles of the anti-hyperglycaemic agent gliclazide in oral tissue-targeted microcapsules in rats,” Scr. Med. (Brno)., vol. 51, no. 1, pp. 15–20, 2020, doi: https://doi.org/10.5937/scriptamed51-25521

[21] J. Patrick, L. Dillaha, D. Armas, and W. C. Sessa, “A randomized trial to assess the pharmacodynamics and pharmacokinetics of a single dose of an extended-release aspirin formulation,” Postgrad. Med., vol. 127, no. 6, pp. 573–580, 2015, doi: 10.1080/00325481.2015.1050341