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Picture courtesy: pharmacy.wsu.edu
"Parenteral" dosing means the administration of therapeutics by intravenous, subcutaneous, intradermal or intramuscular routes. The key factors that are necessities for parenteral formulations are isotonicity, biocompatibility with physiological fluids and tissues, and solubility of the drug in physiological fluids. For intravenous formulations, the solubility of the drug at pH 7.4 in physiological fluids is critically important, since precipitation of the drug after administration can lead to venous irritation, phlebitis, hemolysis and hepatotoxicity. Drugs that have a pka of less than pH 6 are prone to precipitation at pH 7 and higher, due their conversion into a non-ionized form.
To develop a formulation for intravenous delivery, systematic panels of solubility and stability of the drug in various solvent mixes and buffers are constructed, to determine the conditions at which the drug is soluble and physically and chemically stable. The excipients are selected from those already established to have excellent safety profiles in humans. Once prototypes are generated, a specially designed in-vitro flow through apparatus is utilized to simulate the infusion of the drug into physiological fluid and correlated to flow rates. Thus, it is possible to deduce if the formulation is appropriate for a bolus injection, or infusion into peripheral veins. Hemolysis testing is also performed to test the compatibility of the formulation with red blood cells. For drugs that spontaneously precipitate, it is typically recommended that the formulation infusion be through a central vein with high flow rates.
Our teams are experts at determining the adequate conditions for delivering your drug parenterally, by performing the right testing for the route.
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