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Abstract:  Chloral hydrate is a hypnotic, sedative and anxiolytic (non-benzodiazepine) drug that is commonly administered to children prior to procedures such as dental sedation. It is also indicated for nocturnal sedation in all types of patients and especially for the ill, the young, and the elderly patients. A review of the therapeutic uses of chloral hydrate reveals the need for flexibility in dosing, especially in children. However, chloral hydrate is commercially available as a syrup in one fixed strength containing 100-mg/mL. Due to a lack of age-appropriate commercial drug products, an alternative extemporaneously compounded oral liquid from pure drug powder with stability documentation over a bracketed range of 25-mg/mL to 100-mg/mL was developed to provide a flexible, customizable option to meet unique patient needs with convenient and accurate dosing options for pediatric and adult patients. The purpose of the current study was to develop a stability-indicating assay for the analysis of chloral hydrate and to determine the physicochemical and microbiological stability of chloral hydrate in PCCA SuspendIt, a suspending vehicle developed by the Professional Compounding Centers of America (PCCA), Houston, Texas, for use by compounding pharmacists. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. A robust stability-indicating ultra-high-performance liquid chromatographic assay (UPLC) for the determination of the chemical stability of chloral hydrate in PCCA SuspendIt was developed and validated. The study design included two chloral hydrate concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. Solutions of chloral hydrate were prepared from pure drug powder in PCCA SuspendIt at 25-mg/mL and 100-mg/mL concentrations, to represent a range in which the drug is commonly dosed. Samples were stored in amber plastic prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially, and on the following time points (days): 14, 30, 60, 90, and 180. Physical data such as pH and appearance were noted. Samples were also tested for microbiological stability. A stable extemporaneous product is defined as one that retains at least 90% of the label drug concentration throughout the sampling period and is protected against microbial growth. Using this criterion, no significant degradation of the chloral hydrate was observed over the 180-day test period for either concentration at room temperature and in the refrigerator. Drug concentrations were at, or above 96% of the labeled concentrations. No microbial growth was observed. pH values remained fairly constant. This study demonstrates that chloral hydrate is physically, chemically, and microbiologically stable in PCCA SuspendIt for 180 days at room temperature and in the refrigerator at both concentrations studied, thus providing a viable, compounded alternative for chloral hydrate in a liquid dosage form, with an extended BUD to meet patient needs.

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