Pramar Yashoda V, Mandal Tarun K, Bostanian Levon A, Kader Cyndy, Morris Tommy C, Graves Richard A
College of Pharmacy, Xavier University of Louisiana, New Orleans, Louisiana.
Int J Pharm Compd. 2022 Jul-Aug;26(4):342-351.
Amitriptyline hydrochloride is indicated for the relief of symptoms of depression. A review of the therapeutic uses of amitriptyline hydrochloride reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of amitriptyline currently exists. Amitriptyline hydrochloride is commercially available only as 10-mg, 25-mg, 50-mg, 75-mg, 100-mg, and 150-mg tablets. An extemporaneously compounded suspension from pure drug powder would provide a flexible, customizable option to meet unique patient needs with convenient and accurate dosing options. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded amitriptyline hydrochloride suspensions in 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 amitriptyline hydrochloride concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability- indicating high-performance liquid chromatographic assay for the determination of the chemical stability of amitriptyline hydrochloride in PCCA SuspendIt was developed and validated. Suspensions of amitriptyline hydro- chloride were prepared in PCCA SuspendIt at 1-mg/mL and 5-mg/mL concentrations, selected to represent a range within 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): 7, 14, 28, 49, 63, 91, 119, and 185. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was tested. 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 and is protected against microbial growth. The study showed that amitriptyline hydrochloride concentrations did not go below 99.8% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. The pH values remained constant. The viscosity of the suspensions allowed easy re-dispersal of the drug particles upon shaking. This study demonstrates that amitriptyline hydrochloride is physically, chemically, and microbiologically stable in PCCA SuspendIt for 185 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for amitriptyline hydrochloride in a liquid dosage form, with an extended beyond-use date to meet patient needs.
盐酸阿米替林适用于缓解抑郁症状。对盐酸阿米替林治疗用途的回顾表明，给药时需要灵活性。使用口服液体制剂很容易实现这种灵活性。然而，目前尚无盐酸阿米替林的商业液体制剂。盐酸阿米替林仅以10毫克、25毫克、50毫克、75毫克、100毫克和150毫克片剂的形式上市。由纯药物粉末临时配制的混悬液将提供一种灵活、可定制的选择，以满足患者的独特需求，并提供方便、准确的给药方式。本研究的目的是确定在PCCA Base、SuspendIt中临时配制的盐酸阿米替林混悬液的物理化学和微生物稳定性。这种基质是一种无糖、无对羟基苯甲酸酯、无染料、无麸质的触变载体，含有从罗汉果中提取的天然甜味剂。研究设计包括两种盐酸阿米替林浓度，以便在括号内的浓度范围内提供稳定性记录，供配药药师最终使用。开发并验证了一种用于测定PCCA SuspendIt中盐酸阿米替林化学稳定性的稳健的稳定性指示高效液相色谱法。在PCCA SuspendIt中制备浓度为1毫克/毫升和5毫克/毫升的盐酸阿米替林混悬液，所选浓度代表该药物常用的给药范围。样品储存在琥珀色塑料处方瓶中，置于两种温度条件下（5°C和25°C）。最初对样品进行检测，并在以下时间点（天）进行检测：7、14、28、49、63、91、119和185。还记录了诸如pH值、粘度和外观等物理数据。测试了微生物稳定性。所有测量均重复三次。一种稳定的临时产品定义为在整个采样期间至少保留90%初始药物浓度且能防止微生物生长的产品。研究表明，在所研究的两个温度下，盐酸阿米替林浓度均未低于标签声称值（初始药物浓度）的99.8%。未观察到微生物生长。pH值保持恒定。混悬液的粘度使得药物颗粒在摇晃后易于重新分散。本研究表明，盐酸阿米替林在PCCA SuspendIt中在冰箱和室温下185天内物理、化学和微生物性质稳定，从而为盐酸阿米替林提供了一种可行的液体制剂替代品，其超出使用日期延长，以满足患者需求。
