A new esomeprazole packet (sachet) formulation for suspension: in vitro characteristics and comparative pharmacokinetics versus intact capsules/tablets in healthy volunteers

• Published in: Clinical therapeutics 2007-04, Vol.29 (4), p.640-649
• Main Authors: Bladh, Nina, PhD, Blychert, Eva, PhD, Johansson, Karin, PhD, Backlund, Anna, MSc, Lundin, Christina, BSc, Niazi, Mohammad, MSc, Pettersson, Gunilla, PhD, Fjellman, Mia, MSC
• Format: Article
• Language: English
• Subjects: Adult; Anti-Ulcer Agents - administration & dosage; Anti-Ulcer Agents - pharmacokinetics; bioequivalence; Biological and medical sciences; Capsules; Cross-Over Studies; Drug Stability; Esomeprazole - administration & dosage; Esomeprazole - pharmacokinetics; esomeprazole packet; esomeprazole sachet; Female; Humans; Internal Medicine; Male; Medical Education; Medical sciences; Middle Aged; pharmacokinetics; Pharmacology. Drug treatments; reconstitution; suspension stability; Suspensions; Tablets; Therapeutic Equivalency; tube feeding
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2007.03.014

Abstract Background: A packet (sachet) formulation of esomeprazole for suspension has been developed for use in patients who have difficulty swallowing. Objectives: This article reports the in vitro characteristics of the new esomeprazole formulation, including stability in suspension and suitability for administration orally or via enteral tubes. It also describes the pharmacokinetic profile of the esomeprazole 40-mg packet compared with that of existing solid dosage forms (capsules and tablets) in a clinical bioequivalence study. Methods: The stability in suspension of the packet formulation was assessed after reconstitution at various strengths (2.5, 10, and 40 mg) and a different pH (3.4–5.0) in strength-appropriate volumes of water held at temperatures ranging from 5°C to 37°C for up to 60 minutes. Suitability for oral administration was examined in terms of reconstitution time and the actual dose delivered after simulated oral administration, as well as in terms of the actual dose delivered by enteral tubes ranging in diameter from 6 to 20 Fr. Chemical stability and suspension characteristics were also analyzed using alternative reconstitution vehicles (applesauce, apple juice, and orange juice). The comparative pharmacokinetics of the packet, capsule, and tablet formulations of esomeprazole were evaluated in a randomized, open-label, 3-way crossover study in healthy volunteers, who received single 40-mg doses of each formulation. Bioequivalence was assumed if the 90% CIs for the ratios of the geometric mean AUC and CmaX were between 0.80 and 1.25. Reversephase liquid chromatography with ultraviolet detection was used to assess the esomeprazole content and/or degradation products of esomeprazole in the tests for in-suspension stability, dose delivery, and acid resistance. Normal-phase liquid chromatography was used to assess the esomeprazole content of the plasma samples in the bioequivalence study. Results: At the pH and temperature ranges investigated, the packet formulation was stable for up to 60 minutes after reconstitution. Chemical degradation was low (