Development of Enteric Diclofenac Sodium Microparticles Through a Spray-Drying Process Facilitated by Different Aqueous Dispersion Systems

Kanokporn  Burapapadh; Pawanda Warintaksa; Sanphat Ruksapram; Phennapha Saokham

doi:10.59796/jcst.V14N3.2024.53

Authors

Kanokporn Burapapadh Department of Manufacturing Pharmacy, College of Pharmacy, Rangsit University, Pathum Thani 12000, Thailand
Pawanda Warintaksa Department of Manufacturing Pharmacy, College of Pharmacy, Rangsit University, Pathum Thani 12000, Thailand
Sanphat Ruksapram Department of Manufacturing Pharmacy, College of Pharmacy, Rangsit University, Pathum Thani 12000, Thailand
Phennapha Saokham Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200 Thailand

DOI:

https://doi.org/10.59796/jcst.V14N3.2024.53

Keywords:

Enteric coating, Microparticles, Spray-drying, Eudragit® L100, Diclofenac sodium

Abstract

The objective of this study was to prepare enteric diclofenac sodium microparticles using an aqueous dispersion system via spray-drying. Two aqueous-based solvent systems, phosphate buffer at pH 7.0 and ammonium hydrogen carbonate solution, were employed as the feed dispersion media in the spray-drying process based on the solubility characteristics of Eudragit^® L100. At a drug-to-polymer ratio of 1:1, the optimal solids concentration in the feed dispersion was determined to be 2% w/v, as it enabled an approximately 5-30 µm smooth-surfaced spherical microparticle with a high production yield. Diclofenac sodium was efficiently encapsulated within the microparticles, existing as solid dispersion in a partially amorphous form. Notably, the spray-drying conditions utilized in this study obviated the need for further heating for microparticles prepared using ammonium hydrogen carbonate solution, as the residual ammonium could be completely eliminated during the spray-drying process. The two-stage biorelevant drug release profile of enteric microparticles demonstrated their ability to inhibit drug dissolution under acidic conditions while facilitating drug release under basic conditions. The phosphate buffer-based microparticles exhibited greater protection efficiency under acidic conditions compared to ammonium hydrogen carbonate-based systems, despite residual alkaline salt being present in the microparticles. These results validate the potential of the developed microparticles for use as an enteric drug delivery system.

References

Akanny, E., Bourgeois, S., Bonhommé, A., Commun, C., Doleans-Jordheim, A., Bessueille, F., & Bordes, C. (2020). Development of enteric polymer-based microspheres by spray-drying for colonic delivery of Lactobacillus rhamnosus GG. International Journal of Pharmaceutics, 584, Article 119414. https://doi.org/10.1016/j.ijpharm.2020.119414

Al-Ghananeem, A. M., Abbassi, M., Shrestha, S., Raman, G., Wulff, H., Pereira, L., & Ansari, A. (2010). Formulation-based approach to support early drug discovery and development efforts: A case study with enteric microencapsulation dosage form development for a triarylmethane derivative TRAM-34; a novel potential immunosuppressant. Drug Development and Industrial Pharmacy, 36(5), 563–569. https://doi.org/10.3109/03639040903329554

Alhnan, M. A., Kidia, E., & Basit, A. W. (2011). Spray-drying enteric polymers from aqueous solutions: A novel, economic, and environmentally friendly approach to produce pH-responsive microparticles. European Journal of Pharmaceutics and Biopharmaceutics, 79(2), 432–439. https://doi.org/10.1016/j.ejpb.2011.03.015

Alotaibi, H. F., Elsamaligy, S., Mahrous, G. M., Bayomi, M. A., & Mahmoud, H. A. (2019). Design of taste masked enteric orodispersible tablets of diclofenac sodium by applying fluid bed coating technology. Saudi Pharmaceutical Journal, 27(3), 354–362. https://doi.org/10.1016/j.jsps.2018.12.003

Altman, R., Bosch, B., Brune, K., Patrignani, P., & Young, C. (2015). Advances in NSAID development: Evolution of diclofenac products using pharmaceutical technology. Drugs, 75(8), 859–877. https://doi.org/10.1007/s40265-015-0392-z

Can Karaca, A., Guzel, O., & Ak, M. M. (2016). Effects of processing conditions and formulation on spray drying of sour cherry juice concentrate. Journal of the Science of Food and Agriculture, 96(2), 449–455. https://doi.org/10.1002/jsfa.7110

Dalmoro, A., Lamberti, G., Titomanlio, G., Barba, A. A., & D’Amore, M. (2010). Enteric micro-particles for targeted oral drug delivery. An Official Journal of the American Association of Pharmaceutical Scientists, 11(4), 1500–1507. https://doi.org/10.1208/s12249-010-9528-3

El-Badry, M., Alanazi, F. K., Mahrous, G. M., & Alsarra, I. A. (2010). Effects of Kollicoat IR® and hydroxypropyl-β- cyclodextrin on the dissolution rate of omeprazole from its microparticles and enteric-coated capsules. Pharmaceutical Development and Technology, 15(5), 500–510. https://doi.org/10.3109/10837450903300171

Galogahi, F. M., Zhu, Y., An, H., & Nguyen, N. T. (2020). Core-shell microparticles: Generation approaches and applications. Journal of Science: Advanced Materials and Devices, 5(4), 417–435. https://doi.org/10.1016/j.jsamd.2020.09.001

Gan, T. J. (2010). Diclofenac: An update on its mechanism of action and safety profile. Current Medical Research and Opinion, 26(7), 1715–1731. https://doi.org/10.1185/03007995.2010.486301

Gullifa, G., Risoluti, R., Mazzoni, C., Barone, L., Papa, E., Battistini, A., ... & Materazzi, S. (2023). Microencapsulation by a spray drying approach to produce innovative probiotics-based products extending the shelf-life in non-refrigerated conditions. Molecules, 28(2), Article 860. https://doi.org/10.3390/molecules28020860

Jančaitienė, K., & Šlinkšienė, R. (2016). KHPO crystallisation from potassium chloride and ammonium dihydrogen phosphate. Polish Journal of Chemical Technology, 18(1), 1-8. https://doi.org/10.1515/pjct-2016-0001

Khadra, I., Obeid, M. A., Dunn, C., Watts, S., Halbert, G., Ford, S., & Mullen, A. (2019). Characterisation and optimisation of diclofenac sodium orodispersible thin film formulation. International Journal of Pharmaceutics, 561, 43–46. https://doi.org/10.1016/j.ijpharm.2019.01.064

Kincl, M., Meleh, M., Veber, M., & Vrečer, F. (2004). Study of physicochemical parameters affecting the release of diclofenac sodium from lipophilic matrix tablets. Acta Chimica Slovenica, 51, 409-425.

Kusonwiriyawong, C. (2021). Development of spray-dried corn and tapioca starch microparticles for protein delivery. Journal of Current Science and Technology, 11(3), 375-391. https://doi.org/10.14456/jcst.2021.38

Leclair, D. A., Cranston, E. D., Lichty, B. D., Xing, Z., & Thompson, M. R. (2018). Consecutive spray drying to produce coated dry powder vaccines suitable for oral administration. ACS Biomaterials Science and Engineering, 4(5), 1669–1678. https://doi.org/10.1021/acsbiomaterials.8b00117

Lin, S. Y., & Yu, H. L. (1999). Thermal stability of methacrylic acid copolymers of Eudragits L, S, and L30D and the acrylic acid polymer of carbopol. Journal of Polymer Science, Part A: Polymer Chemistry, 37(13), 2061–2067. https://doi.org/10.1002/(SICI)1099-0518(19990701)37:13<2061::AID-POLA20>3.0.CO;2-Y

Nadal, J. M., Gomes, M. L. S., Borsato, D. M., Almeida, M. A., Barboza, F. M., Zawadzki, S. F., ... & Zanin, S. M. W. (2016). Spray-dried Eudragit® L100 microparticles containing ferulic acid: Formulation, in vitro cytoprotection and in vivo anti-platelet effect. Materials Science and Engineering C, 64, 318–328. https://doi.org/10.1016/j.msec.2016.03.086

Nguyen, D. N., Clasen, C., & van den Mooter, G. (2017). Encapsulating darunavir nanocrystals within Eudragit L100 using coaxial electrospraying. European Journal of Pharmaceutics and Biopharmaceutics, 113, 50–59. https://doi.org/10.1016/j.ejpb.2016.12.002

Palomo, M. E., Ballesteros, M. P., & Frutos, P. (1999). Analysis of diclofenac sodium and derivatives. Journal of Pharmaceutical and Biomedical Analysis, 21, 83-94. https://doi.org/10.1016/S0731-7085(99)00089-8

Paudel, A., Worku, Z. A., Meeus, J., Guns, S., & Van den Mooter, G. (2013). Manufacturing of solid dispersions of poorly water soluble drugs by spray drying: formulation and process considerations. International Journal of Pharmaceutics, 453(1), 253–284. https://doi.org/10.1016/j.ijpharm.2012.07.015

Perkušić, M., Nodilo, L. N., Ugrina, I., Špoljarić, D., Brala, C. J., Pepić, I., ... & Hafner, A. (2022). Tailoring functional spray-dried powder platform for efficient donepezil nose-to-brain delivery. International Journal of Pharmaceutics, 624, Article 122038. https://doi.org/10.1016/j.ijpharm.2022.122038

Puccetti, M., Giovagnoli, S., Zelante, T., Romani, L., & Ricci, M. (2018). Development of novel indole-3-aldehyde–loaded gastro-resistant spray-dried microparticles for postbiotic small intestine local delivery. Journal of Pharmaceutical Sciences, 107(9), 2341–2353. https://doi.org/10.1016/j.xphs.2018.04.023

Raffin, R. P., Jornada, D. S., Ré, M. I., Pohlmann, A. R., & Guterres, S. S. (2006). Sodium pantoprazole-loaded enteric microparticles prepared by spray drying: Effect of the scale of production and process validation. International Journal of Pharmaceutics, 324(1), 10–18. https://doi.org/10.1016/j.ijpharm.2006.06.045

Rowe, R.C., Sheskey, P.J., Cook, W.G. & Fenton, M.E. (2012). Handbook of Pharmaceutical Excipients. London, England: Pharmaceutical Press.

Rukari, T., Pingale, P., & Upasani, C. (2023). Vesicular drug delivery systems for the fungal infections’ treatment through topical application-a systemic review. Journal of Current Science and Technology, 13(2), 501-517. https://doi.org/10.59796/jcst.V13N2.2023.1856

Saß, A., & Lee, G. (2014). Evaluation of some water-miscible organic solvents for spray-drying enzymes and carbohydrates. Drug Development and Industrial Pharmacy, 40(6), 749–757. https://doi.org/10.3109/03639045.2013.782554

Singh, A., & van den Mooter, G. (2016). Spray drying formulation of amorphous solid dispersions. Advanced Drug Delivery Reviews, 100, 27–50. https://doi.org/10.1016/j.addr.2015.12.010

Sosnik, A., & Seremeta, K. P. (2015). Advantages and challenges of the spray-drying technology for the production of pure drug particles and drug-loaded polymeric carriers. Advances in Colloid and Interface Science, 223, 40–54. https://doi.org/10.1016/j.cis.2015.05.003

Tang, Y., Arbaugh, B., Park, H., Scher, H. B., Bai, L., Mao, L., & Jeoh, T. (2023). Targeting enteric release of therapeutic peptides by encapsulation in complex coacervated matrix microparticles by spray drying. Journal of Drug Delivery Science and Technology, 79, Article 104063. https://doi.org/10.1016/j.jddst.2022.104063

The United States Pharmacopeial Convention Committee of Revision. (2021a). Buffer solution. USP-NF Online. [Online] Retrieved 27 June 2024.from https://online.uspnf.com/uspnf/document/1_GUID-0E4CE941-0762-456C-94B0-9209A58834FC_3_en-US?source=Activity] accessed on 27 June 2024.

The United States Pharmacopeial Convention Committee of Revision. (2021b). Dissolution<711>. USP-NF Online. [Online] Retrieved 27 June 2024.from https://online.uspnf.com/uspnf/document/1_GUID-AC788D41-90A2-4F36-A6E7-769954A9ED09_3_en-US?source=Search%20Results&highlight=dissolution

Tontul, I., & Topuz, A. (2017). Spray-drying of fruit and vegetable juices: Effect of drying conditions on the product yield and physical properties. Trends in Food Science and Technology, 63, 91–102. https://doi.org/10.1016/j.tifs.2017.03.009

Vehring, R. (2008). Pharmaceutical particle engineering via spray drying. Pharmaceutical Research, 25(5), 999–1022. https://doi.org/10.1007/s11095-007-9475-1

Vicente, J., Pinto, J., Menezes, J., & Gaspar, F. (2013). Fundamental analysis of particle formation in spray drying. Powder Technology, 247, 1–7. https://doi.org/10.1016/j.powtec.2013.06.038

Xu, B., Zhang, W., Chen, Y., Xu, Y., Wang, B., & Zong, L. (2018). Eudragit® L100-coated mannosylated chitosan nanoparticles for oral protein vaccine delivery. International Journal of Biological Macromolecules, 113, 534–542. https://doi.org/10.1016/j.ijbiomac.2018.02.016