FORMULATION AND EVALUATION OF IBUPROFEN PERORAL SUSPENSION 100 mg/5 ml
Keywords:
stable suspension, viscosity, anionic surfactants, biopharmaceutical classification of drugs, class II, risk analysesAbstract
Ibuprofen is a widely used medicine from the group of non-steroidal anti-inflammatory drugs (NSAIDs)
and its development. The development of Ibuprofen oral suspension was in accordance with the requirements
prescribed in possesses analgesic, antipyretic and anti-inflammatory properties. Based on the market analysis, the
properties of the active substance and the intention to cover a pediatric group of patients as a product for
development, an oral suspension was chosen. Due to their thermodynamic instability, formulating a stable
suspension is a complex process followed by many challenges during the ICH Q8 guideline for pharmaceutical
development.
In order to understand the problem of suspensions, as well as to enable easier facing of the challenges during its
development, already in the early phase of the pre-formulation research, risk-based analyzes of changing variables
and process parameters were made on the defined critical characteristics of the product. The realization of the
experiments and all the tests required for the purpose of this paper were carried out in the laboratory premises of the
pharmaceutical company GALAFARM DOO, Skopje, Republic of North Macedonia.
The aim of this paper is the development of a liquid dosage form – a suspension for oral administration, which will
ensure the appropriate release of the prescribed dose of the active substance in the human body. At the same time, it
will meet the prescribed requirements according to the appearance, viscosity, color, smell and taste to be acceptable
to the target group of patients - children from 3 months to 12 years, as well as chemical and physical characteristics
and to ensure the stability of the active substance. For this purpose, four formulations of Ibuprofen oral suspension
100 mg /5 ml were made where the main variables were the suspending agents/viscosity adjustment. The anionic
surfactant polysorbate 80 was also taken as a variable, which is of crucial importance, primarily because it is a class
II active substance according to the biopharmaceutical classification of drugs. The samples were evaluated
according to the appropriate tests prescribed in the current editions of the European Pharmacopoeia [PhEur.], the
British Pharmacopoeia [BP] and the United States Pharmacopoeia [USP], and some of the parameters were also
tested according to the company's internal methods. From the tested formulations, only with formulation 2, 3 and 4
were obtained results that satisfy the requirements prescribed in the quality specification for Ibuprofen oral
suspension 100 mg/5 ml, but the most acceptable organoleptic characteristics, appearance, consistency and taste
were achieved by formulation 3, which was chosen for further and additional investigations.
References
Bostijn, N., Renterghem, J.V., Dhondt, W., Vervaet, C., & Beer, T.D. (2018). A continuous manufacturing concept for a pharmaceutical oral suspension. European Journal of Pharmaceutical Sciences, 123, 576–583.
Bushra, R., & Aslam, N. (2010). An overview of clinical pharmacology of Ibuprofen. Oman Medical Journal, 25(3), 155–1661. doi:10.5001/omj.2010.49
Council of Europe. European Pharmacopoeia. 11th ed. Strasbourg: Council of Europe; (2022). Ibuprofen; p.3062-3064
Gaikwad, S. S., Morales, J. O., Lande, N. B., Catalán-Figueroa, J., Laddha, U. D., & Kshirsagar, S. J. (2024). Exploring paediatric oral suspension development: Challenges, requirements, and formulation advancements. International journal of pharmaceutics, 657, 124169. https://doi.org/10.1016/j.ijpharm.2024.124169
International Conference on Harmonization. (2009). ICH Q8 (R2): Pharmaceuical Development. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, 8(August), 28. https://www.ich.org/page/quality-guidelines
Jadav, M., Pooja, D., Adams, D. J., & Kulhari, H. (2023). Advances in Xanthan Gum-Based Systems for the Delivery of Therapeutic Agents. Pharmaceutics, 15(2), 402. https://doi.org/10.3390/pharmaceutics15020402
Koshani, R., Tavakolian, M., & van de Ven, T. G. M. (2020). Cellulose-based dispersants and flocculants. J. Mater. Chem. B, 8(46), 10502–10526. https://doi.org/10.1039/D0TB02021D
Kumar, P., & Verma, M. (2023). Pharmaceutical Suspensions: An Updated Patent Review on Novel Suspending Agents and Recent Advancement. Recent advances in drug delivery and formulation, 17(3), 193–209. https://doi.org/10.2174/0126673878246149231010085610
Lopalco, A., & Denora, N. (2020). Paediatric Formulation: Design and Development. International journal of molecular sciences, 21(19), 7118. https://doi.org/10.3390/ijms21197118
Potthast, H., Dressman, J. B., Junginger, H. E., Midha, K. K., Oeser, H., Shah, V. P., Vogelpoel, H., & Barends, D. M. (2005). Biowaiver monographs for immediate release solid oral dosage forms: ibuprofen. Journal of pharmaceutical sciences, 94(10), 2121–2131. https://doi.org/10.1002/jps.20444
Sheskey, P. J., Hancock, B. C., Moss, G. P., Goldfarb, D. J., & American Pharmacists Association. (2020). Handbook of pharmaceutical excipients (Ninth edition). Pharmaceutical Press ; American Pharmacists Association.
Sinko, P. J. (2013). Coarse dispersions. In Martin's Physical Pharmacy and Pharmaceutical Sciences: Physical Chemical and Biopharmaceutical Principles in the Pharmaceutical Sciences: Sixth Edition (pp. 410-441). Wolters Kluwer Health Adis (ESP).
