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Tolerability of hypertonic injectables.
1BioTherapeutics Pharmaceutical Sciences, Pfizer Inc. 700 Chesterfield Parkway West, Chesterfield, MO 63017, United States; Wang Biologics, LLC, 907 Wellesley Place, Chesterfield, MO 63017, United States.
International Journal of Pharmaceutics
|June 2, 2015
Summary
Hypertonic injectable drugs can cause pain and irritation, with severity depending on osmolality and injection site. Recommended upper limits are provided to minimize patient discomfort during drug administration.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery
- Biocompatibility
Background:
- Injectable drug products are ideally isotonic, but hypertonic formulations are sometimes necessary for drug solubility and stability.
- Hypertonicity in injectable products raises concerns regarding patient tolerability, including local and systemic side effects.
Purpose of the Study:
- To review and discuss the tolerability of hypertonic injectable drug products.
- To identify factors influencing side effects and establish osmolality limits for different injection routes.
Main Methods:
- Review of in-vitro, in-vivo animal, and human model data on hypertonicity-induced side effects.
- Analysis of pain and discomfort associated with various injection routes (intramuscular, subcutaneous, intravenous).
Main Results:
- Side effects of hypertonicity, such as pain and irritation, are dose-dependent.
- Pain sensation generally follows the order: intramuscular > subcutaneous > intravenous/intravascular.
Conclusions:
- Recommended upper osmolality limits: <600 mOsm/kg for intramuscular/subcutaneous injections.
- Recommended upper osmolality limits: <1000 mOsm/kg for small-volume (<100 mL) intravenous/intravascular injections and <500 mOsm/kg for large-volume (>100 mL) injections.
- Strategies exist to minimize pain associated with hypertonic injectable products.
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