Development of an omeprazole parenteral formulation with hydroxypropyl-beta-cyclodextrin.
Because of both the low solubility and stability of omeprazole in an aqueous environment, cyclodextrins (CDs) were added as inclusion complexation agents and stability enhancers in a parenteral formulation. Stability curves of omeprazole in different aqueous media were compared to determine which was most appropriate to prepare a formulation. The aimed preparation contains 40 mg omeprazole in an as low a volume of solvent as possible. A first assay in 40% hydroxypropyl-beta-cyclodextrin (HP-beta-CD) at pH 7.4 and 8.0 was not successful because degradation occurred before omeprazole was completely dissolved. Another manufacturing method was therefore tested. It concerned the use of an ammonia-based solvent in which omeprazole easily dissolved at high pH values, but a lower pH was reached after lyophilization. The inclusion capability of different cyclodextrins (CDs), suitable for parenteral use, was compared. The preparations that were finally selected (i.e., 40 mg omeprazole in 10 mL of a 40% HP-beta-CD ammonia/water-solution with an initial pH of 11 or 12, were found, after lyophilization, to be in agreement with the requirements for parenterals.
Holvoet
Chantal
C
Department of Analytical Chemistry and Pharmaceutical Technology, Vrije Universiteit Brussel-VUB, Laarbeeklaan, Brussels, Belgium.
Heyden
Yvan Vander
YV
Plaizier-Vercammen
Jacqueline
J
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000641:Ammonia / Q000737:chemistry; D000897:Anti-Ulcer Agents / Q000032:analysis / Q000138:chemical synthesis* / Q000737:chemistry; D002021:Buffers; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D004333:Drug Administration Routes; D004355:Drug Stability; D005612:Freeze Drying; D006863:Hydrogen-Ion Concentration; D009853:Omeprazole / Q000032:analysis / Q000737:chemistry*; D012995:Solubility; D012996:Solutions; D012997:Solvents; D013997:Time Factors; D047392:beta-Cyclodextrins / Q000032:analysis / Q000138:chemical synthesis* / Q000737:chemistry
D000897:Anti-Ulcer Agents; D002021:Buffers; D012996:Solutions; D012997:Solvents; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000641:Ammonia; D009853:Omeprazole