Physicochemical Stability of Compounded Amlodipine Besylate Suspensions in PCCA Base, SuspendIt

Abstract

Amlodipine besylate is an antihypertensive agent recommended for the management of hypertension in children and adolescents. The commercially available 2.5-mg, 5-mg, and 10-mg amlodipine besylate tablets do not provide the necessary flexibility in dosing needed for treating children. This flexibility is readily achieved using an oral, liquid dosage form. However, no commercial liquid dosage form of amlodipine currently exists. An extemporaneously compounded suspension from pure drug powder or commercial tablets would provide a convenient option to meet unique patient needs. The purpose of this study was to determine the physicochemical stability of extemporaneously compounded amlodipine besylate suspensions in the PCCA Base, SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two amlodipine besylate concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stabilityindicating high-performance liquid chromatographic assay for the determination of the chemical stability of amlodipine besylate in SuspendIt was developed and validated. Suspensions of amlodipine were prepared in SuspendIt at 0.5-mg/mL and 10.0-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in plastic amber prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially, and at the following time points: 7 days, 14 days, 29 days, 46 days, 60 days, 90 days, 120 days, and 180 days. Physical data such as pH, viscosity, and appearance were also noted. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period. This study demonstrates that amlodipine besylate is physically and chemically stable in SuspendIt for 90 days in the refrigerator and 7 days at room temperature, retaining 90% of the label claim (initial drug concentration) at both concentrations. The pH values did not change significantly. The viscosity of the refrigerated samples at both concentrations decreased slightly, while that of the room temperature samples showed a marked increase in viscosity. This study provides a viable, compounded alternative for amlodipine in a liquid dosage form, with an adequate beyond-use-date to meet patient needs. The study further provides stability documentation over a bracketed amlodipine concentration range of 0.5 mg/mL to 10.0 mg/mL, allowing compounding pharmacists more flexibility in customizing their formulations.