Long-Term Stability of Glycopyrrolate Oral Solution Galenic Compound at Different Storage Conditions

Abstract

Glycopyrrolate is a competitive muscarinic receptor antagonist used in the treatment of sialorrhea, especially in pediatrics. Degradation research was conducted to better understand the stability of the active pharmaceutical ingredient (API). Using an HPLC-UV method, we evaluated the chemical stability of the oral solution of the galenic compound glycopyrrolate 0.5 mg/mL under different storage conditions. Method validation was performed according to the International Council for Harmonization (ICH) Q2(R2) guidelines. The results of the stability study of the galenic compound in different storage conditions, with the exception of those stored in glass containers at 45 °C for more than 3 months, were stable (100 ± 10% of the nominal concentration). The aim of this work was to study the stability of the galenic compound glycopyrrolate in two different types of containers and at three different storage temperatures. Glycopyrrolate showed degradation beyond the limits only in glass at 45 °C and after 2 months of storage. The results indicate that oral liquid dosage forms of glycopyrrolate are stable for at least 210 days when stored at room temperature or at 4 °C, in glass or PET, for at least 7 months, maintaining product quality according to the standards established by the European Pharmacopoeia, ensuring long-term coverage for pediatric patient therapies.

Keywords: clinical galenic; drug compounding; drug stability; glycopyrrolate; pediatrics; pharmaceutical; pharmacopoeia; safety; sialorrhea.

Figure 1

Glycopyrronium bromide IUPAC: (1,1-dimethylpyrrolidin-1-ium-3-yl) 2-cyclopentyl-2-hydroxy-2-phenylacetate;bromide (https://pubchem.ncbi.nlm.nih.gov/compound/11693 accessed on 19 July 2024).

Figure 2

Nipagin sodium, also methylparaben sodium, IUPAC: sodium;4-methoxycarbonylphenolate (https://pubchem.ncbi.nlm.nih.gov/compound/23663626 accessed on 19 July 2024).

Figure 3

Chromatograms related to the HPLC-UV analysis of the IS azathioprine (A), the preservative nipagin (B), the glycopyrrolate (C), and the galenic compound added with IS (D).

Figure 4

Linearity assessment with error bars and fitting results—mean values from 3 replicates.

Figure 5

Mean concentration (μg/mL) of glycopyrrolate in galenic compound dispensed in glass or PET containers and stored at +4 °C, room temperature (RT), and +45 °C. Full line represents the initial nominal concentration; dashed line is the lower limit of acceptable concentration according to the directives set out in the European Pharmacopoeia.

Figure 6

Alpha-cyclopentylmandelic acid, IUPAC: 2-cyclopentyl-2-hydroxy-2-phenylacetic acid (https://pubchem.ncbi.nlm.nih.gov/compound/98283 accessed on 19 July 2024).