Compatibility studies between mannitol and omeprazole sodium isomers

Agatonovic-Kustrin, S., Markovic, N., Ginic-Markovic, M., Mangan, M., and Glass, B.D. (2008) Compatibility studies between mannitol and omeprazole sodium isomers. Journal of Pharmaceutical and Biomedical Analysis, 48 (2). pp. 356-360.

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Abstract

Omeprazole, commonly used in the treatment of various gastrointestinal disorders degrades rapidly in acidic pHs and results in inter-individual variability due to different rates of metabolism amongst patients. Since S-omeprazole shows more predictable bioavailability and excipients have been known to interact with active pharmaceutical ingredients to produce altered bioavailability, it was decided to investigate the compatibility of omeprazole sodium isomers with mannitol, the major excipient in omeprazole formulations using differential scanning calorimetry (DSC) for bulk drug, attenuated total reflectance (ATR) infrared (IR) spectroscopy in a powder mixture and localized thermal analysis (LTA) from a drug disk.

DSC results clearly indicate an interaction between mannitol and R-omeprazole sodium due to decreased melting temperatures and broadening peaks. The DSC of S-omeprazole sodium does not show melting temperature although the drug was crystalline. Because of the accelerated temperature conditions during DSC experiments applied in this work, ATR-IR was undertaken to determine whether these results occurred at room temperature for the solid dosage form. The ATR-IR results show a difference between R- and S-omeprazole sodium with mannitol by the appearance of both the amino (N–H) and imino (=N–H) stretching frequencies for R-omeprazole and only the N–H for the S-omeprazole sodium. It may thus be concluded that different ratios for the tautomeric forms for S- and R-omeprazole sodium result in changes in the degree of crystallinity and are responsible for the interaction with mannitol, common excipient in formulation. These interactions may be directly related to the difference in terms of bioavailability.

Item ID: 6652
Item Type: Article (Refereed Research - C1)
Keywords: omeprazole sodium isomers; mannitol; differential scanning calorimetry; attenuated total reflectance infrared; spectroscopy; localized thermal analysis; polymorphism; tautomerism
ISSN: 1873-264X
Date Deposited: 08 Feb 2010 00:26
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1115 Pharmacology and Pharmaceutical Sciences > 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9299 Other Health > 929999 Health not elsewhere classified @ 100%
Citation Count from Web of Science Web of Science 7
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