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Published on: March 11, 2017
An In Vitro Study of the Physicochemical Stability of Ropivacaine and Dexamethasone Formulations Containing Different
Heezoo Kim1, So Young Lee1, Chung Hun Lee1
1Department of Anesthesiology and Pain Medicine, Korea University Medical Center, Guro Hospital, Seoul, Republic of Korea.
Background:
Previous studies evaluating the stability of ropivacaine and dexamethasone mixtures used in epidural steroid injections have reported inconsistent findings regarding the presence, morphology, and size of crystals.
Objectives:
We sought to evaluate the physicochemical stability of ropivacaine combined with 3 dexamethasone formulations; each formulation had different preservatives. We also sought to identify a preservative that allows for a physicochemically more stable and thus safer co-administration than those prone to crystal formation.
Study Design:
Our in vitro study compared the physicochemical stabilities of ropivacaine and 3 dexamethasone formulations containing different preservatives.
Setting:
A university medical center laboratory.
Methods:
Mixtures were prepared by combining 0.75% ropivacaine with each of 3 dexamethasone formulations (Formulation 1: glycerin, disodium edetate, sodium hydroxide, and phosphoric acid; Formulations 2 and 3: same components plus benzyl alcohol). All were mixed in a 1:1 ratio in polypropylene syringes and stored at 24°C. The mixtures were evaluated for visual and microscopic changes, pH, and drug concentration for up to 2 hours using high-performance liquid chromatography.
Results:
No macroscopic crystal formation was observed in any mixtures. The concentration of both drugs as well as the pH of each mixture remained stable for 2 hours post mixing. Mixtures of ropivacaine and dexamethasone without benzyl alcohol showed no linear crystals upon microscopic examination, whereas the ropivacaine and dexamethasone mixture containing benzyl alcohol formed multiple linear crystals (10 μm-20 μm) immediately after mixing, continuing for 2 hours.
Limitations:
The physicochemical stability of drugs observed in vitro does not guarantee unchanged pharmacokinetics and pharmacodynamics in vivo.
Conclusion:
Preservatives in dexamethasone formulations may affect the physicochemical stability of ropivacaine and dexamethasone mixtures. Formulations without benzyl alcohol may offer greater compatibility, highlighting the need for preinjection evaluation of drug mixtures and the development of clinical guidelines for safe co-administration.
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