Can azithromycin oral suspension be kept in the refrigerator?

Comment by InpharmD Researcher

Per the prescribing information, azithromycin (both mono- and dihydrate) oral suspension can be stored between 5-30°C (41-86°F). Stability studies have further confirmed the stability of azithromycin oral suspension for up to 15 days under refrigerated conditions; however, the FDA labeling suggests using the suspension within 10 days.

Background

A 2024 pharmaceutical stability assessment evaluated the chemical stability of azithromycin in a reconstituted oral suspension under various in-home storage conditions over a 10-day period. Azithromycin suspensions (AZRO® 200 mg/5 mL; Sanofi, Türkiye) were prepared using boiled tap water and stored at six different conditions: refrigeration (3–6°C), room temperature (20–25°C), three elevated temperatures (30°C, 40°C, and 50°C), and direct sunlight exposure (temperature fluctuating between 25–50°C with 20–60% relative humidity). Daily high-performance liquid chromatography (HPLC) analyses quantified azithromycin concentrations in triplicate. The concentration-time curves and statistical analyses compared azithromycin concentrations on days 0 and 10 across all conditions. The findings showed azithromycin demonstrated robust chemical stability in all tested storage conditions with no significant degradation over the 10-day period [see Table 1 for full results]. HPLC data showed that azithromycin concentrations remained within acceptable variations (<5% change from baseline) even at 50°C and under direct sunlight exposure. Chromatographic analysis confirmed the absence of major degradants or loss of active pharmaceutical ingredient integrity, suggesting that azithromycin powder for reconstitution maintains stability despite suboptimal storage. However, the authors emphasized the need for further investigations into the physicochemical and organoleptic properties of the suspension, including potential changes in color, odor, or texture, which could impact patient adherence and therapeutic efficacy. [1]

A 2017 investigation evaluated the stability and efficacy of three commonly prescribed pediatric antibiotic suspensions, including cefuroxime axetil, amoxicillin-clavulanate potassium, and azithromycin, under distinct storage conditions following reconstitution. The study systematically assessed antibiotic degradation over a five-day period by employing a validated UV/Vis spectroscopic method to quantify active drug concentrations. Reconstituted suspensions were stored in three different conditions: refrigeration at 2-8°C (condition A), room temperature inside a cupboard between 25-29°C (condition B), and submersion in water at room temperature between 22-25°C (condition C). Periodic sampling was performed on days 1, 3, and 5, with concentration calculations derived using the Beer-Lambert law. The findings demonstrated that refrigeration maintained drug stability, with percentage concentrations remaining within 90 ± 5% up to day 5. In contrast, samples stored in a cupboard at room temperature exhibited extensive degradation, with concentrations falling below 80% by day 5. [2]

For condition A, all antibiotics were stable for the first three days. Azithromycin and cefuroxime axetil remained stable until the fifth day, but amoxicillin-clavulanate potassium showed slight degradation on the fifth day. Condition B demonstrated the least stability, with degradation observed by the third day for all antibiotics and extensive degradation by the fifth day. Condition C maintained stability for three days, with degradation observed on the fifth day. The study's findings align with previous research, suggesting that refrigerated storage conditions help maintain stability better than room temperature. [2]

A 2018 study evaluated a novel approach for masking the bitter taste of azithromycin in a dry suspension dosage form using titanium dioxide nanoparticles (TNPs) through physisorption. The investigation utilized a series of characterization techniques to confirm the adsorption of TNPs onto the surface of azithromycin. The resulting nanohybrid formulation exhibited significant taste-masking properties, as validated through human panel testing and in vitro dissolution studies at saliva pH (6.8) and intestinal pH (7.4). The Langmuir adsorption isotherm demonstrated a saturation point at which no further nanoparticle adsorption occurred, confirming the optimal formulation. The optimized nanohybrid (AZN-7) was subsequently formulated into a dry suspension and subjected to stability studies under both dry and reconstituted conditions. The reconstituted samples were kept at refrigeration for 14 days. The optimized suspension (F6) displayed excellent palatability, effectively masking the bitter taste while maintaining a dissolution rate comparable to the marketed azithromycin formulation at intestinal pH. Comparative dissolution testing demonstrated a retarded release in saliva-like conditions attributed to the insolubility of the titanium dioxide nanolayer at this pH, thereby reducing interaction with taste receptors. Stability studies over 90 days showed that both the dry and reconstituted suspensions maintained chemical integrity and physical stability. The product's long-term stability was attributed to TNP adsorption, which also helped the reconstituted suspension remain within specifications for 15 days under refrigeration, likely by protecting the drug from light. The investigation concluded that the physisorption strategy using TNPs is a promising approach for improving the palatability of azithromycin without compromising its bioavailability or therapeutic efficacy. [3]

References:

[1] Gokbulut C, Sari OF, Akyol BA, Sen F, Geyguc N. The stability of azithromycin in a reconstituted oral suspension under various in-home storage conditions. Pharm Chem J. 2024;57(11):1841-1847. doi: 10.1007/s11094-024-03087-0
[2] Stanley C, Igala S. Effect of different storage conditions on the stability and efficacy of some reconstituted oral antibiotic suspensions sold in port harcourt, nigeria. JPRI. 2018;20(3):1-10. doi: 10.9734/JPRI/2017/38553
[3] Amin F, Khan S, Shah SMH, et al. A new strategy for taste masking of azithromycin antibiotic: development, characterization, and evaluation of azithromycin titanium nanohybrid for masking of bitter taste using physisorption and panel testing studies. Drug Des Devel Ther. 2018;12:3855-3866. Published 2018 Nov 8. doi:10.2147/DDDT.S183534

Relevant Prescribing Information

Storage: Store dry powder below 30°C (86°F). After mixing, store suspension at 5° to 30°C (41° to 86°F) and use within 10 days. Discard after full dosing is completed. [4], [5]

References:

[4] Zithromax (azithromycin dihydrate powder, for suspension). Prescribing information. Pfizer; 2025.
[5] Azithromycin monohydrate powder for suspension. Prescribing information. Taro Pharmaceuticals U.S.A., Inc.; 2024.

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Can azithromycin oral suspension be kept in the refrigerator?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→



Please see Table 1 for your response.


 

Mean Concentrations of Reconstituted Azithromycin Oral Suspensions from Different In-home Storage Conditions from Gokbulut et al. (2024)

Days Refrigerator (3-6°C) Sun Exposure 50°C 40°C 30°C 20 - 25°C
0 2.01 ± 0.01 1.99 ± 0.00 2.02 ± 0.00 2.08 ± 0.01 2.09 ± 0.07 2.04 ± 0.01
1 1.95 ± 0.04 1.95 ± 0.07 1.98 ± 0.10 1.99 ± 0.07 2.12 ± 0.10 2.03 ± 0.01
2 1.99 ± 0.11 2.07 ± 0.11 1.95 ± 0.13 2.03 ± 0.12 2.10 ± 0.14 2.03 ± 0.12
3 1.94 ± 0.05 1.98 ± 0.17 1.93 ± 0.09 1.98 ± 0.09 2.07 ± 0.06 1.97 ± 0.06
4 1.91 ± 0.14 1.95 ± 0.22 2.05 ± 0.12 2.00 ± 0.04 2.09 ± 0.21 1.95 ± 0.10
5 2.07 ± 0.16 2.07 ± 0.22 2.05 ± 0.13 1.93 ± 0.07 2.10 ± 0.18 2.02 ± 0.12
6 1.93 ± 0.05 2.02 ± 0.04 2.12 ± 0.06 2.01 ± 0.05 2.10 ± 0.04 2.03 ± 0.08
7 2.03 ± 0.03 2.02 ± 0.04 2.10 ± 0.16 2.09 ± 0.12 2.09 ± 0.10 2.04 ± 0.02
8 1.96 ± 0.07 2.00 ± 0.06 2.06 ± 0.10 2.01 ± 0.07 2.10 ± 0.06 2.13 ± 0.14
9 2.17 ± 0.11 2.11 ± 0.07 2.17 ± 0.04 2.08 ± 0.06 2.07 ± 0.12 2.05 ± 0.08
10 2.03 ± 0.12 2.04 ± 0.16 1.98 ± 0.18 2.10 ± 0.12 2.07 ± 0.08 2.09 ± 0.07

 

References:

Gokbulut C, Sari OF, Akyol BA, Sen F, Geyguc N. The stability of azithromycin in a reconstituted oral suspension under various in-home storage conditions. Pharm Chem J. 2024;57(11):1841-1847. doi: 10.1007/s11094-024-03087-0