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Abstract:  The pharmaceutical landscape in pediatric cardiology involves the use of several key active pharmaceutical ingredients (APIs) that have been carefully selected to address the diverse range of conditions encountered. Hydrochlorothiazide, captopril and metoprolol are part of this list, selected based on stringent criteria that included proven efficacy, a favorable safety profile, and suitability for pediatric use. These active ingredients belong to different pharmacological groups - an angiotensin-converting enzyme inhibitor (captopril), a thiazide diuretic (hydrochlorothiazide) and a beta-blocker (metoprolol) – and are used to treat a variety of cardiovascular problems. Commercial pharmaceutical forms of these drugs are not available for pediatric patients, leaving a gap in dosing options. Therefore, the primary means of serving this population is through extemporaneous compounding of suspensions using pure drug powder or commercial tablets. The objective of this study was to investigate the physicochemical and microbiological stability of three distinct compounded pediatric oral cardiovascular suspensions, that contain captopril, hydrochlorothiazide, and metoprolol tartrate, and are formulated using PCCA SuspendIt. The study design included two concentrations of each API to provide stability investigation over a bracketed concentration range: captopril (1 mg/mL and 5 mg/mL), hydrochlorothiazide (5 mg/mL and 10 mg/mL), and metoprolol (1 mg/mL and 10 mg/mL). Ultra-high-performance liquid chromatography (UHPLC) methods were developed and validated for the determination of the chemical stability of captopril, hydrochlorothiazide, and metoprolol in SuspendIt. Samples of hydrochlorothiazide and metoprolol suspensions were stored in plastic amber prescription bottles at the temperature 25±2 °C, relative humidity 60±5 %, and captopril suspensions at 5±3 °C. Samples were analyzed at the following time points: 0, 7, 14, 30, 60, 90, and 180 days. Various forced degradation conditions were employed, including acidic, basic, oxidative, and heat degradation. The results revealed that potential interfering degradants do not affect the analytical peaks of the drug substance, and the factors contributing to the significant degradation of the drug substance in the suspension were identified. Physical properties such as pH and appearance were also observed. All measurements were performed in duplicate. Antimicrobial efficacy tests were performed to control microbial growth during storage. The current study demonstrates that SuspendIt cardiovascular suspensions are physically, chemically and microbiologically stable for 180 days for captopril (when stored in the refrigerator) and hydrochlorothiazide and metoprolol tartrate (when stored at room temperature), retaining not less than 90% of the labeled drug concentrations. This study provides a viable compounded alternative for hydrochlorothiazide, metoprolol tartrate and captopril in a liquid dosage form with an adequate beyond-use-date to meet patient needs.

Related Categories: PEDIATRICS, STABILITIES, COMPATIBILITIES, CARDIOLOGY, DOSAGE FORMS/DRUG CARRIERS

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