Stability study of a Betaxolol Oral Suspension Hospital Preparation

Introduction
Betaxolol (BTX) is a cardioselective β-blocker used in pediatrics, off-label, in the dynamic exploration of somatotropic function. Due to the lack of a pharmaceutical suitable for children, a hospital preparation of a 1 mg/mL BTX oral suspension (OS) was developed, and a stability study was conducted.
The objective of this work is to study the physicochemical and microbiological stability of BTX oral suspensions over time, to establish their expiration dates based on their storage conditions.

Materials et methods
The stability study was conducted on 3 batches of 20 bottles, produced by 3 different operators. We studied 3 storage conditions and performed triplicate samplings at regular intervals: 4-8°C sealed bottles (T0, T7, T15, T30, T45, T60, and T90), 4-8°C opened bottles (T0, T7, T15, T30), and 20-25°C sealed bottles (T0, T7, T15).

The physicochemical stability was monitored by determining the active ingredient content and semi-quantitative monitoring of impurities and degradation products by HPLC, pH measurement, and viscosity measurement. According to the US Pharmacopeia recommendations, a parameter is considered stable if it varies by less than 10% from the reference value measured at T0. The increase of any impurity must be less than the threshold value of 0.2%.

The microbiological stability was monitored by microbial enumeration (direct seeding) and by the test for efficacy of antimicrobial preservation. According to the European Pharmacopeia (EP), threshold values are below 200 CFU/mL for aerobic microbials (TAMC) and below 20 CFU/mL for yeasts and molds (TYMC). Bottles submitted to the antimicrobial preservation test were intentionally contaminated, and a 3-log reduction was expected for TAMC and a 1-log reduction for TYMC.

Results
Viscosity, pH, and content measurements were compliant under each storage conditions and each sampling times, except at day 90 for sealed bottles stored at 4-8°C, for which the percentage deviation of content compared to T0 was greater than 10%. We note the formation of a degradation product below the threshold value. This product had been identified during the forced degradation study by oxidation, and is due to the presence of dissolved oxygen in the oral suspension. The microbiological results were compliant with EP specifications at each analysis times.

Conclusion
BTX oral suspensions (1 mg/mL) made with Syrspend^® SF PH4 liquid are stable at 4-8°C for 60 days when sealed and 30 days after opening. We have also shown that the preparations are stable for 14 days at room temperature, which is an important information in case of a cold chain break.

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