Method Development for the Quantification of Erythromycin in 250 mg Capsules

Background / Introduction
Erythromycin is a macrolide antibiotic used off-label for its gastric emptying acceleration properties. The pharmaceutical specialty ERY 250mg, previously used for this indication, has not been available on the market since 2023, and currently, there is no available oral form on the market.

Objectives / Purpose
The aim of this work is to address this gap by developing a new oral preparation of erythromycin capsules in the non-sterile compounding unit.

Methods
A stability-indicating method using reversed-phase high-performance liquid chromatography (RP-HPLC) paired with a diode-array UV detector was developed and validated per ICH Q2 (R1) guidelines. The parameters of precision, accuracy, linearity, and specificity were evaluated. The chromatographic system (HPLC) included a Polaris C18 column, a mobile phase consisting of acetonitrile and a 20 mM phosphate buffer at pH 8 (40/60, v/v); the flow rate was set at 1.5 mL/min with an injection volume of 20 µL. The concentration range was set between 8 and 12 mg/mL and validated using three quality control levels at 8.5, 10, and 11.5 mg/mL. A forced degradation study under acidic, basic, and oxidative conditions was conducted. Visual inspection of the peak and UV spectrum between 200 and 400 nm showed no degradation products co-eluting with erythromycin. The chosen formulation was 250 mg base erythromycin capsules.

Results
We obtained pure erythromycin capsules (250 mg API) in size 0. The assay method was linear between 8 and 12 mg/mL (R² > 0.99), accurate (recovery rates between 100,42 and 101,35 %, relative error <1.1% across all control points), precise (CV < 2%), and repeatable (n = 10, CV < 1.2%). It was validated per ICH Q2 (R1) criteria. The forced degradation study showed degradation in acidic (0.01 M HCl; degraded 26.7%), basic (0.1 M NaOH; degraded 34.9%), and oxidative (1.5% H₂O₂; degraded 100%) media. None of the detected degradation products co-eluted with erythromycin under any of the tested conditions. Moreover, no deformation of the peak or UV spectrum was observed by the diode array detector.

Conclusion
The method is validated per ICH Q2 (R1) guidelines. A forced degradation study under milder oxidative conditions still needs to be conducted before a full stability study can begin. The development of a suspension, more appropriate for a pediatric use, is being considered as a follow-up to this work.

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