Wallach Jason, Gamrat James, Jauhola-Straight Rebekah, Becker Jeffrey, Eckrich Thomas
Department of Pharmaceutical Sciences, University of the Sciences, Philadelphia, PA 19104, USA.
Bexson Biomedical Inc., Santa Barbara, CA 93108, USA.
Pharmaceutics. 2022 Mar 3;14(3):556. doi: 10.3390/pharmaceutics14030556.
Subcutaneous (SC) ketamine has been found to be effective in pain management, though reports of injection site irritation and sterile abscesses exist with currently available ketamine HCl formulations. Such adverse SC reactions are commonly associated with low pH, high osmolality and/or high injection volumes. An optimal SC formulation of ketamine would thus have a pH and osmolality close to physiological levels, without compromising on concentration and, thus, injection volume. Such a formulation should also be buffered to maintain the pH at the acceptable level for extended time periods. As many of these physicochemical properties are interrelated, achieving these aims represented a significant challenge in formulation development. We describe the development of a novel Captisol-based formulation strategy to achieve an elevated pH, isosmotic and buffered formulation of ketamine (hence, three birds, one excipient) without compromising on concentration. This strategy has the potential to be readily adapted to other amine-based APIs.
皮下注射氯胺酮已被证明在疼痛管理中有效，不过目前可用的盐酸氯胺酮制剂存在注射部位刺激和无菌脓肿的报告。此类皮下不良反应通常与低pH值、高渗透压和/或高注射体积有关。因此，理想的氯胺酮皮下制剂的pH值和渗透压应接近生理水平，同时不影响浓度，进而不影响注射体积。这种制剂还应进行缓冲，以便在较长时间段内将pH值维持在可接受水平。由于许多这些物理化学性质相互关联，在制剂开发中实现这些目标是一项重大挑战。我们描述了一种基于Captisol的新型制剂策略的开发，以实现氯胺酮的高pH值、等渗和缓冲制剂（因此，一举三得，一种辅料），同时不影响浓度。该策略有可能很容易地应用于其他胺基活性药物成分。
