Kostecka D, Duncan M R, Wagenknecht D
Fujisawa USA, Incorporated, Melrose Park, IL 60160, USA.
PDA J Pharm Sci Technol. 1998 Nov-Dec;52(6):320-5.
Clonidine Hydrochloride Injection (Duraclon) is a clear, colorless, preservative-free, pyrogen free, aqueous solution of clonidine hydrochloride. The indication for this product is for use as an adjunct in pain management, administered epidurally, when opiates are insufficient. The drug formulation was evaluated under both normal and stress conditions in the preformulation/formulation studies. The list of studies conducted includes a light sensitivity study, an oxygen sensitivity study, a pH/stability study, a stopper compatibility evaluation, a freeze-thaw study, and a stability study. Samples from the light, oxygen, pH/stability, and stability studies were evaluated for color, visual clarity, pH, potency, and chromatographic purity. Samples from the freeze-thaw study were evaluated for all of the above except chromatographic purity. The results for these studies demonstrate the stability of the product as formulated. The pH of this unbuffered product was consistently within the acceptance criteria. The product remained clear and colorless for the duration of each study. The values obtained for the potency and chromatographic purity assays showed no evidence of degradation. The reasons for the lack of degradation can be found in the molecular structure of the drug substance and the formulation of the drug product. Since the molecular structure is that of a Schiff base, it is theoretically possible, although difficult, to cleave the molecule. A catalyst would be required, and none of the possible catalysts are present in the formulation. The molecule could also be cleaved upon exposure to light, and the evidence indicates that the molecule does interact with light. This interaction is not to the degree, however, that product stability is affected. The formulation contains only the active drug substance and sodium chloride in water for injection with a pH of approximately 6. Although the product is unbuffered, the influence of the stoppers and glass vials upon the formulation pH was minimal. In addition, the stopper compatibility of the product is enhanced by the absence of chelating agents, preservatives, acids, and bases. Since the dilute concentrations of both the active and excipient are well below their solubility limits, no solubility related issues would be expected upon freezing and subsequent thawing. Clonidine Hydrochloride Injection, as formulated, does not require protection from light, oxygen, or freezing. The product shows acceptable stability within the pH range, and the rubber closure is compatible with the product. Real time stability data combined with statistical projections support a 36-month expiration date.
盐酸可乐定注射液（杜拉氯铵）是一种澄清、无色、无防腐剂、无热原的盐酸可乐定水溶液。本品的适应症是在阿片类药物不足时，作为硬膜外给药用于疼痛管理的辅助药物。在处方前/处方研究中，对该药物制剂在正常和应激条件下进行了评估。所进行的研究包括光敏感性研究、氧敏感性研究、pH/稳定性研究、瓶塞相容性评估、冻融研究和稳定性研究。对光、氧、pH/稳定性和稳定性研究的样品进行了颜色、视觉清晰度、pH、效价和色谱纯度的评估。对冻融研究的样品进行了除色谱纯度之外的上述所有评估。这些研究结果证明了所配制产品的稳定性。该无缓冲产品的pH始终在可接受标准范围内。在每项研究期间，产品均保持澄清无色。效价和色谱纯度测定所获得的值未显示降解迹象。缺乏降解的原因可在药物分子结构和药物制剂中找到。由于分子结构为席夫碱，理论上虽然难以实现，但有可能裂解该分子。这需要一种催化剂，而制剂中不存在任何可能的催化剂。该分子在光照下也可能裂解，证据表明该分子确实与光相互作用。然而，这种相互作用的程度并未影响产品稳定性。该制剂仅含有活性药物成分和注射用水中的氯化钠，pH约为6。尽管该产品无缓冲，但瓶塞和玻璃瓶对制剂pH的影响极小。此外，由于不存在螯合剂、防腐剂、酸和碱，该产品的瓶塞相容性得到增强。由于活性成分和辅料的稀释浓度远低于其溶解度极限，预计冷冻和随后解冻时不会出现与溶解度相关的问题。所配制的盐酸可乐定注射液不需要避光、避氧或防冻。该产品在pH范围内显示出可接受的稳定性，并且橡胶密封件与产品相容。实时稳定性数据与统计预测结果支持36个月的有效期。
