Solid Dosage Forms with Fixed-Dose Combinations of Active Pharmaceutical Ingredients: Therapeutic Importance and Review of Formulation Strategies

Nevena Maksimović; Jelena Đuriš

doi:10.5937/arhfarm76-67662

Nevena Maksimović University of Belgrade – Faculty of Pharmacy, Department of Pharmaceutical Technology and Cosmetology, Belgrade, Serbia
Jelena Đuriš University of Belgrade – Faculty of Pharmacy, Department of Pharmaceutical Technology and Cosmetology, Belgrade, Serbia

DOI: https://doi.org/10.5937/arhfarm76-67662

Keywords: fixed-dose combinations, formulation approaches, clinical significance

Abstract

Fixed-dose combination (FDC) products contain at least two active pharmaceutical ingredients (APIs) in a single dosage form. Monolithic, multilayer, and multiparticulate formulations are widely employed in the manufacture of solid fixed-dose combination products, such as tablets and capsules. Among the technologies used in production, active film coating, compression coating and liquid dispensing technology are the most widely employed, with increasing attention being given to 3D printing of FDC products. Selecting the appropriate formulation strategy for the development of these drugs is crucial to minimising their disadvantages. Clinically, they offer improved efficacy, safety, and tolerability in the treatment of conditions such as hypertension, type 2 diabetes, tuberculosis, pain, various infections, hormonal disorders and contraception. From the patient’s perspective, they provide practicality and simplify therapy by reducing pill burden, which leads to greater adherence and, consequently, improved therapeutic outcomes and quality of life.

References

Fernández-García R, Prada M, Bolás-Fernández F, Ballesteros MP, Serrano DR. Oral fixed-dose combination pharmaceutical products: Industrial manufacturing versus personalized 3D printing. Pharm Res. 2020;37(7):1–22.

Kim DW, Weon KY. Pharmaceutical application and development of fixed-dose combination: Dosage form review. J Pharm Investig. 2021;51(5):555–70.

Desai D, Wang J, Wen H, Li X, Timmins P. Formulation design, challenges, and development considerations for fixed dose combination (FDC) of oral solid dosage forms. Pharm Dev Technol. 2013;18(6):1265–76.

Drumond N, Stegemann S. Better medicines for older patients: Considerations between patient characteristics and solid oral dosage form designs to improve swallowing experience. Pharmaceutics. 2020;13(1):32.

Wilkins CA, Hamman H, Hamman JH, Steenekamp JH. Fixed-dose combination formulations in solid oral drug therapy: advantages, limitations, and design features. Pharmaceutics. 2024;16(2):178.

Zhang Q, Chan DXH, HO KY. Efficacy and safety of fixed-dose combinations for pain in older adults. Drugs Aging. 2024;41(11):873–9.

Narita K, Hoshide S, Kario K. Seasonal variation in blood pressure: current evidence and recommendations for hypertension management. Hypertens Res. 2021;44(11):1363–72.

Warmelink I, ten Hacken NH, van der Werf TS, van Altena R. Weight loss during tuberculosis treatment is an important risk factor for drug-induced hepatotoxicity. Br J Nutr. 2011;105(3):400–8.

Sahota T, Della Pasqua O. Feasibility of a fixed-dose regimen of pyrazinamide and its impact on systemic drug exposure and liver safety in patients with tuberculosis. Antimicrob Agents Chemother. 2012;56(11):5442–9.

Agencija za lekove i medicinska sredstva Srbije [Internet]. Beograd: ALIMS; c2026 [cited 2026 June 11]. Available from: https://www.alims.gov.rs/humani-lekovi/pretrazivanje-humanih-lekova/.

Messerli FH, Williams B, Ritz E. Essential hypertension. Lancet. 2007;370(9587):591–603.

Sica DA. Rationale for fixed-dose combinations in the treatment of hypertension. Drugs. 2002;62(3):443–62.

Hypertension: Developing Fixed-Combination Drug Products for Treatment. Food and Drug Administration [Internet]. Silver Spring (MD): U.S. Food and Drug Administration, Center for Drug Evaluation and Research; c2018 [cited 2026 May 24]. Available from: https://www.fda.gov/media/117975/download.

An J, Derington CG, Luong T, Olson KL, King JB, Bress AP, Jackevicius CA. Fixed-dose combination medications for treating hypertension: A review of effectiveness, safety, and challenges. Curr Hypertens Rep. 2020;22(11):1–19.

Vijayakumar TM, Jayram, J, Cheekireddy VM, Himaja D, Teja YD, Narayanasamy D. Safety, efficacy, and bioavailability of fixed-dose combinations in type 2 diabetes mellitus: a systematic updated review. Curr Ther Res Clin Exp. 2017;84:4–9.

Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32:193–203.

Blonde L, San Juan ZT. Fixed-dose combinations for treatment of type 2 diabetes mellitus. Adv Ther. 2012;29(1):1–13.

Panchagnula R, Agrawal S, Ashokraj Y, Varma M, Sateesh K, Bhardwaj V, et al. Fixed dose combinations for tuberculosis: lessons learned from clinical, formulation and regulatory perspective. Methods Find Exp Clin Pharmacol. 2004;26(9):703–21.

Blomberg B, Spinaci S, Fourie B, Laing R. The rationale for recommending fixed-dose combination tablets for treatment of tuberculosis. Bull World Health Organ. 2001;79(1):61–8.

Pergolizzi Jr JV, van de Laar M, Langford R, Mellinghoff HU, Merchante IM, Nalamachu S, et al. Tramadol/paracetamol fixed-dose combination in the treatment of moderate to severe pain. J Pain Res. 2012;5:327.

O’Brien J, Pergolizzi Jr JV, van de Laar M, Mellinghoff HU, Merchante IM, Nalamachu S, et al. Fixed-dose combinations at the front line of multimodal pain management: perspective of the nurseprescriber. Nursing (Auckl). 2013;3:9–22.

Worthington RJ, Melander C. Combination approaches to combat multidrug-resistant bacteria. Trends Biotechnol. 2013;31(3):177–84.

Todd PA, Benfield P. Amoxicillin/clavulanic acid. Drugs. 1990;39(2):264–307.

Hall KS, Trussell J. Types of combined oral contraceptives used by US women. Contraception. 2012;86(6):659–65.

Cooper DB, Patel P, Mahdy H. Oral contraceptive pills. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2017 [cited 2026 May 20]. Available from: https://europepmc.org/article/NBK/nbk430882.

De Melo NR. Estrogen-free oral hormonal contraception: benefits of the progestin-only pill. Women’s Health (Lond). 2010;6(5):721–35.

Janczura M, Sip S, Cielecka-Piontek J. The Development of Innovative Dosage Forms of the Fixed-Dose Combination of Active Pharmaceutical Ingredients. Pharmaceutics. 2022;14(4):834.

Seo KS, Bajracharya R, Lee SH, Han HK. Pharmaceutical application of tablet film coating. Pharmaceutics. 2020;12(9):853.

Gowthami B, Krishna SG, Rao DS. Application of coating technology to chronotherapeutic drug delivery systems: Recent publications and patents. Curr Res Pharmacol Drug Discov. 2021;2:100015.

Clarke A, Doughty D. Development of liquid dispensing technology for the manufacture of low dose drug products. In: Kleinebudde P, Khinast J, Rantanen J, editors. Continuous manufacturing of pharmaceuticals. Hoboken, New Jersey: John Wiley & Sons; 2017; pp. 551–75.

Seoane-Viaño I, Trenfield SJ, Basit AW, Goyanes A. Translating 3D printed pharmaceuticals: From hype to real-world clinical applications. Adv Drug Deliv Rev. 2021;174:553–75.

Keerikkadu M, Chennamsetty S, Shetty A, Tippavajhala VK, Rathnanand M. 3D-printed polypills for personalized medicine and precision oral drug delivery in pharmaceutical practice: A review. Int J Pharm X. 2025;11:100474.