Dual-release capsule of pseudoephedrine and cetirizine for reduced dosing frequency and improved therapy

Kosasih Kosasih; Lully Marlinda

doi:10.35814/jifi.v24i2.2074

Penulis

Kosasih Kosasih Pharmaceutic Departement, Faculty of Pharmacy, Universitas Pancasila, Jakarta, 12640, Indonesia
Lully Marlinda Pharmaceutic Departement, Faculty of Pharmacy, Universitas Pancasila, Jakarta, 12640, Indonesia

DOI:

https://doi.org/10.35814/jifi.v24i2.2074

Kata Kunci:

Cetirizine, dissolution profile, immediate‑release, pseudoephedrine, sustained‑release

Abstrak

Pseudoephedrine hydrochloride is a sympathomimetic agent acting on α‑ and β‑adrenergic receptors with a half‑life of 5–8 h, requiring multiple daily doses. Sustained‑release formulations are desirable to maintain therapeutic plasma concentrations, reduce dosing frequency, and minimize fluctuations. Cetirizine dihydrochloride, a long‑acting non‑sedating antihistamine with a half‑life of ~10 h, is suitable for immediate‑release dosage forms. This study aimed to develop a dual‑release capsule containing pseudoephedrine hydrochloride sustained‑release granules and cetirizine dihydrochloride immediate‑release granules. Ethyl cellulose N100 was employed as a coating agent, while starch served as a disintegrant. The granule mixture exhibited acceptable physicochemical properties, with moisture content of 4.185–4.513%, flow rate of 10.63–12.30 g/s, and angle of repose between 23.78°–27.53°. Capsule content uniformity ranged from 97.15–98.45% for pseudoephedrine hydrochloride and 99.33–104.61% for cetirizine dihydrochloride. Dissolution testing revealed two distinct release profiles. Cetirizine dihydrochloride showed dissolution behavior comparable to the reference product, whereas pseudoephedrine hydrochloride exhibited significant differences. In conclusion, combining sustained‑release pseudoephedrine hydrochloride with immediate‑release cetirizine dihydrochloride in a single capsule is feasible. Further optimization is required to align pseudoephedrine hydrochloride release with the reference product.

Referensi

[1] S. A. Bhalerao, G. A. Dhonde, S. S. Muley, and S. D. Kolhe, “A review: Formulation and evaluation of sustained release tablet,” Quest J. J. Res. Pharm. Sci., vol. 10, no. 4, pp. 74–79, 2024.

[2] N. S. Randil, T. P. Shangrapawar, A. Bhosale, R. Gaikwad, and K. Waster, “Advancements in sustained release tablet formulations: A comprehensive review,” Int. J. Res. Technol. Innov., vol. 9, no. 4, pp. 807–811, 2024.

[3] G. Pharande, S. More, V. M. Satpute, and S. R. Ghodake, “Formulation and evaluation of sustained release tablets,” Int. J. Pharm. Sci., vol. 3, no. 1, pp. 1070–1072, 2025, doi: 10.5281/zenodo.14643179.

[4] M. Nilesh, M. Abhishek, P. Rajeshwari, and N. A. Mane, “Formulation and evaluation of fast disintegrating tablet of cetirizine hydrochloride,” Int. J. Pharm. Res. Appl., vol. 8, no. 5, pp. 1254–1264, 2024, doi: 10.35629/7781-080512541264.

[5] ClinicalTrials.eu, “Cetirizine dihydrochloride – application in therapy and current clinical research,” 2025. [Online]. Available: https://clinicaltrials.eu

[6] U.S. Food and Drug Administration, “Drug safety communication: Cetirizine and levocetirizine labeling update,” 2025. [Online]. Available: https://www.fda.gov

[7] H. Harahap, B. Prasaja, and R. Sari, “Single-dose bioequivalence of cetirizine–pseudoephedrine extended-release tablet formulations assessed in healthy subjects,” J. Int. Res. Med. Pharm. Sci., vol. 3, no. 1, pp. 1–8, 2015.

[8] S. Kushare, A. Phatak, and P. Chaudhari, “Development and evaluation of a novel modified release pellet-based system for desloratadine and pseudoephedrine hydrochloride,” Asian J. Pharm., vol. 18, no. 2, pp. 112–120, 2024.

[9] CN110974807A, “Cetirizine pseudoephedrine sustained-release capsule and preparation method thereof,” Chinese Patent Publication, 2025.

[10] R. Reid, J. Smith, K. Patel, and T. Johnson, “Development and validation of HPLC methods for antihistamines: Application to cetirizine and pseudoephedrine,” J. Pharm. Biomed. Anal., vol. 234, pp. 115–123, 2024.

[11] S. B. Subramanya, B. Ramesh, and A. Kumar, “Spectrophotometric determination of cetirizine dihydrochloride in pharmaceutical formulations,” Int. J. Pharm. Sci. Rev. Res., vol. 64, no. 2, pp. 45–50, 2020.

[12] Drawell Analytical, “Sample preparation for FTIR analysis: Sample types and prepare methods.” [Online]. Available: https://www.drawellanalytical.com/sample-preparation-for-ftir-analysis-sample-types-and-prepare-methods/

[13] Shimadzu Corporation, “Liquid samples – FTIR analysis basics.” [Online]. Available: https://www.shimadzu.com

[14] Chemistry LibreTexts, “Interpreting infrared spectra,” in Organic Chemistry (Morsch et al.). [Online]. Available: https://chem.libretexts.org

[15] A. H. Ahmad Nadzri et al., “Source determination of pseudoephedrine using attenuated total reflectance Fourier transform infrared spectroscopy combined with chemometric analysis,” Malays. J. Anal. Sci., vol. 24, no. 2, pp. 233–240, 2020. [Online]. Available: https://mjas.analis.com.my/mjas/v24_n2/pdf/Ainol_24_2_14.pdf

[16] S. M. Osman and I. O. Abu Reid, “Analytical techniques for the determination of pseudoephedrine combinations with non sedating H1 antihistamines in pharmaceutical dosage forms,” J. Glob. Health Sci., vol. 6, no. 2, p. e18, 2024, doi: 10.35500/jghs.2024.6.e18.

[17] M. Kumar and S. D. Kolhe, “Forced degradation studies of cetirizine hydrochloride, phenylephrine hydrochloride, paracetamol by RP-HPLC,” Int. J. Res. Pharm. Pharm. Sci., vol. 6, no. 5, pp. 20–23, 2021. [Online]. Available: https://www.pharmacyjournal.in/assets/archives/2021/vol6issue5/6-5-15-989.pdf (pharmacyjournal.in in Bing)

[18] N. D. Rawool, A. Venkatchalam, and K. H. Singh, “Development and validation of a rapid RP-HPLC method for the simultaneous estimation of cetirizine and pseudoephedrine in pharmaceutical dosage forms,” Int. J. Curr. Pharm. Res., vol. 5, no. 1, pp. 54–60, 2013.

[19] K. Abu-Shandi et al., “Simultaneous determination of cetirizine and pseudoephedrine combined in tablet dosage form by high performance liquid chromatography,” Jordan J. Pharm. Sci., vol. 6, no. 2, pp. 188–202, 2013, doi: 10.12816/0000366.

[20] United States Pharmacopeial Convention, “Chromatography—General chapter <621>,” in United States Pharmacopeia and National Formulary (USP 47–NF 42), 2023.

[21] R. R. Tadikonda and J. Alwala, “Stability studies of cetirizine dihydrochloride in aqueous solution using UV spectrophotometry,” Int. J. Pharm. Sci. Res., vol. 14, no. 5, pp. 2100–2107, 2023, doi: 10.13040/IJPSR.0975-8232.14.5.2100-20107.

[22] A. A. Ali and T. Elsaman, “Stability and degradation kinetics of pseudoephedrine hydrochloride in aqueous solutions,” J. Appl. Pharm. Sci., vol. 11, no. 7, pp. 120–127, 2021, doi: 10.7324/JAPS.2021.110716.

[23] M. I. Khan et al., “Development and validation of stability indicating assay method of cetirizine hydrochloride by HPLC,” Afr. J. Pharm. Pharmacol., vol. 5, no. 2, pp. 143–149, 2011, doi: 10.5897/AJPP10.283.

[24] United States Pharmacopeia, General Chapter <921> Water Determination. Rockville, MD: USP Convention, 2023. [Online]. Available: http://ftp.uspbpep.com/v29240/usp29nf24s0_c921.html (ftp.uspbpep.com in Bing)

[25] S. Tasnim, M. F. K. Tipu, M. S. Rana, M. A. Rahim, M. Haque, M. S. Amran, A. A. Chowdhury, and J. A. Chowdhury, “Modification of bulk density, flow property and crystallinity of microcrystalline cellulose prepared from waste cotton,” Materials, vol. 16, no. 16, p. 5664, 2023, doi: 10.3390/ma16165664.

[26] S. R. Henson, M. N. Hasan, J. K. Drennen, and C. A. Anderson, “Increasing continuous granulation process understanding: principal component analysis of granule size distributions,” Int. J. Pharm., vol. 681, p. 125897, 2025, doi: 10.1016/j.ijpharm.2025.125897.

[27] T.-L. Vu, S. Nezamabadi, and S. Mora, “Effects of particle compressibility on structural and mechanical properties of compressed soft granular materials,” J. Mech. Phys. Solids, vol. 46, p. 104201, 2021, doi: 10.1016/j.jmps.2020.104201.

[28] G. Cole, J. Hogan, and M. E. Aulton, “Pharmaceutical Capsules,” in Aulton’s Pharmaceutics: The Design and Manufacture of Medicines, 5th ed., K. Taylor, Ed. London, UK: Elsevier, 2020, pp. 505–528.

[29] European Pharmacopoeia Commission, European Pharmacopoeia 11.0: Granules—tests for flow properties, compressibility, and particle size distribution. Strasbourg: Council of Europe, 2023.

[30] United States Pharmacopeial Convention, USP 43–NF 38: General Chapter <905> Uniformity of Dosage Units. Rockville, MD: USP Convention, 2020.

[31] United States Pharmacopeial Convention, USP 43–NF 38: General Chapter <701> Disintegration. Rockville, MD: USP Convention, 2020.

[32] United States Pharmacopeial Convention, USP 43–NF 38: Assay—Content determination of cetirizine and pseudoephedrine by HPLC. Rockville, MD: USP Convention, 2020.

[33] United States Pharmacopeial Convention, USP 47–NF 42: General Chapter <711> Dissolution. Rockville, MD: USP Convention, 2023.

[34] European Directorate for the Quality of Medicines & HealthCare, European Pharmacopoeia (11th ed.): Dissolution Testing of Solid Oral Dosage Forms. Strasbourg, France: Council of Europe, 2023.

[35] M. Ali et al., “Applications of UV-Vis and FTIR spectroscopy in pharmaceutical analysis,” J. Pharm. Biomed. Anal., vol. 186, p. 113509, 2020, doi: 10.1016/j.jpba.2020.113509.

[36] A. Rohman et al., “UV-Vis and FTIR spectroscopy in pharmaceutical and biomedical analysis,” Pharmaceuticals, vol. 14, no. 9, p. 872, 2021, doi: 10.3390/ph14090872.

[37] “Cetirizine dihydrochloride,” SpectraBase. [Online]. Available: https://spectrabase.com/compound/3RqqfSQgkMA (spectrabase.com in Bing). Accessed: Jan. 12, 2025.

[38] G. F. Faturachman, A. A. Ramanda, S. Maharani, L. A. Latif, G. A. G. Belo, and S. A. A. Ayubi, “Application of Fourier transform infrared spectroscopy (FTIR) for quantitative analysis of pharmaceutical compounds,” Indones. J. Pharm., vol. 5, no. 1, pp. 27–33, 2025, doi: 10.37311/ijpe.v5i1.23309.

[39] B. Stuart, Infrared Spectroscopy: Fundamentals and Applications. Wiley, 2021.

[40] I. O. Abu Reid, “Experimental design optimized chromatographic determination of pseudoephedrine and fexofenadine in bulk and tablets,” Pharm. Chem. J., vol. 56, no. 3, 2023, doi: 10.1007/s11094-023-02808-1.

[41] S. Subramanya Raj Urs, M. Bindu, D. Ramyashree, and K. N. Sowmya, “Spectrophotometric method for the estimation of cetirizine hydrochloride in pharmaceutical preparation,” Asian J. Pharm. Anal., vol. 10, no. 4, pp. 185–188, 2020, doi: 10.5958/2231-5675.2020.00034.4.

[42] ICH, Validation of Analytical Procedures: Text and Methodology Q2(R1). International Council for Harmonisation, 2005.

[43] ICH, Validation of Analytical Procedures: Text and Methodology Q2(R2). International Council for Harmonisation, 2020.

[44] K. Kosasih and F. Weningtyas, “Capsule dosage forms containing natural antioxidant microcapsules of Cantigi extract,” J. Health Med. Sci., vol. 7, no. 2, pp. 41–50, 2024, doi: 10.31014/aior.1994.07.02.317.

[45] K. Kosasih, D. Susanty, I. P. H. Asianski, and D. I. Maryanto, “Formulation and characterization of antioxidant capsules containing cantigi extract-loaded nanoparticles synthesized via nanoprecipitation method,” J. Nat. Prod. Degener. Dis., vol. 1, no. 2, pp. 79–85, 2024, doi: 10.58511/jnpdd.v1i2.6352.

[46] R. Voigt, Lehrbuch der pharmazeutischen Technologie, 12th ed. Deutscher Apotheker Verlag, 2007.

[47] L. Lachman, H. A. Lieberman, and J. L. Kanig, The Theory and Practice of Industrial Pharmacy, 3rd ed. Lea & Febiger, 1986.

[48] M. E. Aulton and K. M. G. Taylor, Aulton’s Pharmaceutics: The Design and Manufacture of Medicines, 5th ed. Elsevier, 2018.

[49] T. Casian, S. Iurian, A. Gâvan, A. Porfire, A. L. Pop, S. Crișan, A. M. Pușcaș, and I. Tomuță, “In-depth understanding of granule compression behavior under variable raw material and processing conditions,” Pharmaceutics, vol. 14, no. 1, p. 177, 2022, doi: 10.3390/pharmaceutics14010177.

[50] United States Pharmacopeial Convention, USP 47–NF 42: General Chapter <616> Bulk density and tapped density of powders. Rockville, MD: USP Convention, 2023.

[51] United States Pharmacopeial Convention, USP 47–NF 42: General Chapter <786> Particle size distribution estimation by analytical sieving. Rockville, MD: USP Convention, 2023.

[52] M. E. Aulton and K. Taylor, Aulton’s Pharmaceutics: The Design and Manufacture of Medicines, 5th ed. Elsevier, 2018; S. Pradhan *et al

[52] S. Pradhan et al., “Fundamentals of Pharmaceutical Granulation Technology,” Int. J. Pharm. Pharmacol. Res., 2023.

[53] United States Pharmacopeial Convention, United States Pharmacopeia and National Formulary (USP 47–NF 42): General Chapter <621> Chromatography. Rockville, MD: USP Convention, 2023.

[54] B. T. Alquadeib, “Development and validation of a new HPLC analytical method for the determination of diclofenac in tablets,” Saudi Pharm. J., vol. 27, no. 1, pp. 66–70, 2019, doi: 10.1016/j.jsps.2018.07.020.

[55] Indonesian Pharmacopoeia Commission, Farmakope Indonesia Edisi IV. Jakarta: Departemen Kesehatan Republik Indonesia, 1995.

[56] United States Pharmacopeial Convention, USP 47–NF 42: General Chapter <701> Disintegration. Rockville, MD: USP Convention, 2023.

[57] European Pharmacopoeia Commission, European Pharmacopoeia, 11th Edition: Disintegration of tablets and capsules (2.9.1). Strasbourg: Council of Europe, 2023.

[58] European Pharmacopoeia Commission, European Pharmacopoeia, 11th Edition: Disintegration of tablets and capsules (2.9.6). Strasbourg: Council of Europe, 2023.

[59] British Pharmacopoeia Commission, British Pharmacopoeia, 3rd ed. London: The Stationery Office, 2001.