[Visual documentation of the stability of intravenous solutions of omeprazole (Losec) and pantoprazole (Pantoloc)].
Patients with complications of peptic ulcers, high grade reflux oesophagitis, or Zollinger Ellison syndrome need a sufficient permanent acid suppression. In appropriate indications they receive proton pump inhibitors (PPI) intravenously or via perfusion over a longer period, if an oral application is not possible. PPIs are prodrugs, which should be converted into the active principle in the acidic canaliculus at pH 1 of the parietal cell. Otherwise they would be activated prematurely. Immediate chemical degradation causes discolouration. Aim of the study was to compare pH stabilities of the intravenous formulations of Omeprazole (different solutions for infusion and injection) and Pantoprazole (one solution for injection and infusion). The solutions prepared accordingly to the official instructions, were exposed to four different light conditions. Both manufacturers (AstraZeneca Osterreich GmbH, Byk Osterreich Pharma Ges.m.b.H.) state reference solutions for acceptable discolouration. Those were prepared according to the European Pharmacopeia. Discolouration of solutions were evaluated as criterion for stability of the PPI prodrugs. If change of colour is at least of the extent of the corresponding reference solution, further use is no longer permitted. Optical alterations under different light conditions were compared and documented photographically with standardized illumination. Intensity and spectral composition of light as well as temperature had only minor influence on discolouration as measure of degradation of the prodrugs. Both formulations for injection fulfill the specifications for pH stability within the stated time frames mentioned in the summaries of product characteristics (SPC). Comparing both products, after a short period (1 hour) Omeprazole injectable formulation showed a substantial optical discolouration. After 6 hours these changes were more intense than the reference solution BG5 allows. Pantoprazole showed optical alteration to a notable later time point. After 24 hours discolouration reached the reference colour B6. Injectable formulation of Pantoprazole is about three times more stable than that of Omeprazole. Infusion solution of Omeprazole shows no optical alteration within the stated time frame due to high dilution and pH value. Assuming that 100 ml of the infusion solution contains 40 mg Omeprazole. It takes 5 hours for the volume to be infused at a dose regimen of 8 mg/h. Therefor 5 x 100 ml/24 h are needed.
Leitner
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Institut für Analytische Chemie, Universität Wien, Währinger Strasse 38, A-1090 Wien. leitner@anc.univie.ac.at
Zöllner
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D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000737:chemistry*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000737:chemistry*; D004355:Drug Stability; D004356:Drug Storage; D004942:Esophagitis, Peptic / Q000188:drug therapy*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007262:Infusions, Intravenous; D009853:Omeprazole / Q000008:administration & dosage / Q000737:chemistry*; D000077402:Pantoprazole; D010437:Peptic Ulcer / Q000188:drug therapy*; D054328:Proton Pump Inhibitors; D013329:Structure-Activity Relationship; D013454:Sulfoxides / Q000008:administration & dosage / Q000737:chemistry*; D015043:Zollinger-Ellison Syndrome / Q000188:drug therapy*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D054328:Proton Pump Inhibitors; D013454:Sulfoxides; D000077402:Pantoprazole; D009853:Omeprazole