Wegmans School of Pharmacy, St. John Fisher College, Rochester, NY 14618, USA.
Ann Pharmacother. 2010 Mar;44(3):462-5. doi: 10.1345/aph.1M647. Epub 2010 Feb 11.
Rufinamide is an oral antiepileptic drug indicated for adjunctive therapy in treating generalized seizures associated with Lennox-Gastaut syndrome. Currently, rufinamide is available as 200-mg and 400-mg tablets. A liquid dosage form does not exist at the present time. Lack of a suspension formulation may present an administration problem for many children and adults who are unable to swallow tablets. The availability of a liquid dosage form will provide an easy and accurate way to measure and administer the medication.
To determine the stability of both sugar-containing and sugar-free rufinamide suspensions over a 90-day period.
A suspension of rufinamide 40 mg/mL was prepared by grinding twelve 400-mg tablets of rufinamide tablets in a glass mortar. Sixty milliliters of Ora-Plus and 60 mL of either Ora-Sweet or Ora-Sweet SF (sugar free) were mixed and added to the powder to make a final volume of 120 mL. Three identical samples of each formulation were prepared and placed in 60-mL amber plastic bottles and were stored at room temperature. A 1-mL sample was withdrawn from each of the 6 bottles with a micropipette immediately after preparation and at 7, 14, 28, 56, and 90 days. After further dilution to an expected concentration of 0.4 mg/mL, the samples were assayed using high-performance liquid chromatography. Stability was defined as the retention of at least 90% of the initial concentration.
At least 90% of the initial rufinamide concentration remained throughout the 90-day study period in both preparations. There were no detectable changes in color, odor, taste, and pH and no visible microbial growth.
Extemporaneously compounded suspensions of rufinamide 40 mg/mL in a 1:1 mixture of Ora-Plus and Ora-Sweet or Ora-Sweet SF were stable for at least 90 days when stored in 59-mL amber polypropylene plastic bottles at room temperature.
鲁非酰胺是一种口服抗癫痫药物，适用于辅助治疗与 Lennox-Gastaut 综合征相关的全身性癫痫发作。目前，鲁非酰胺有 200mg 和 400mg 片剂。目前还没有液体剂型。对于许多无法吞咽片剂的儿童和成人来说，缺乏混悬剂可能会带来给药问题。液体剂型的出现将提供一种简单、准确的测量和给药方式。
确定含有糖和无糖鲁非酰胺混悬液在 90 天内的稳定性。
通过在玻璃研钵中研磨 12 片 400mg 鲁非酰胺片剂，制备 40mg/mL 的鲁非酰胺混悬液。将 60 毫升 Ora-Plus 和 60 毫升 Ora-Sweet 或 Ora-Sweet SF（无糖）混合并加入粉末中，使最终体积达到 120 毫升。制备了 3 种相同的每种制剂的样品，并将其放置在 60 毫升琥珀色塑料瓶中，在室温下储存。用微量移液器从每个 6 个瓶子中取出 1 毫升样品，立即制备后以及在 7、14、28、56 和 90 天。进一步稀释至预期浓度 0.4mg/mL 后，使用高效液相色谱法对样品进行测定。稳定性定义为至少保留初始浓度的 90%。
在整个 90 天的研究期间，在两种制剂中，初始鲁非酰胺浓度至少保留了 90%。颜色、气味、味道和 pH 值没有任何可检测到的变化，也没有可见的微生物生长。
当在室温下储存在 59 毫升琥珀色聚丙烯塑料瓶中时，以 Ora-Plus 和 Ora-Sweet 或 Ora-Sweet SF 的 1:1 混合物配制的 40mg/mL 鲁非酰胺临时混悬液至少稳定 90 天。
