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Preservative Effectiveness of a Novel Formulation of Intravenous Epoprostenol, Administered Under Ambient Conditions, for Pulmonary Arterial Hypertension

L. Wichey-Lakshmanan

N. Palepu

B. B. Teja

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Conference: 2010 International PHA Conference and Scientific Sessions

Release Date: 06.24.2010

Presentation Type: Abstracts

Witchey-Lakshmanan L1, Palepu N2, Teja BB3
1. GeneraMedix Pharmaceuticals, Inc., Liberty Corner, NJ, USA 
2. SciDose LLC, Amherst, MA, USA 
3. TherDose Pharma Pvt. Ltd., Kukatpally, Hyderabad, India

BACKGROUNDCurrently marketed formulations of intravenous epoprostenol used to treat pulmonary arterial hypertension are thermo-liable requiring the use of ice packs to maintain stability during drug administration. A formulation of epoprostenol with improved stability when administered at room temperature (RT) should decrease complications associated with compound degradation and improve quality of life for patients. In addition, long term administration of intravenous prostanoids has been linked to sepsis and injection site infections. Here we examined preservative effectiveness of a new formulation of epoprostenol, with improved stability at ambient temperatures in both the reconstituted state in the vial (0.3 mg/mL) and the fully diluted state (15,000 ng/mL) ready for administration.

METHODSThe United States Pharmacopeia (USP) Antimicrobial Effectiveness Test (AET) was performed directly in each reconstituted vial (with 5mL of sterile water) by immediate inoculation with 105 to 106 cfu/mL of test organism. Sampling was timed as required in the USP AET. For fully diluted admixtures, a modified USP AET was used to mimic in-use handling. One vial of drug product was diluted to 100 mL of admixed solution and immediately inoculated with ~10cfu/mL of the test organism, a level used to mimic microbe concentrations which might be typical of a diluted solution. Organisms used were those as indicated in the USP AET.

RESULTSThe reconstituted formulation passed the USP AET criteria for self-preserving at 7 days, 14 days and 28 days when inoculated with bacteria, yeast, and mold. The fully admixed solution also showed no microbial proliferation.

CONCLUSIONSBoth in the reconstituted and in the fully diluted states, this formulation of intravenous epoprostenol does not support microbial growth.