The effect of the composition of a fixed dose combination on bioequivalence results
Language English Country Netherlands Media print-electronic
Document type Clinical Trial, Journal Article
PubMed
29758343
DOI
10.1016/j.ijpharm.2018.05.030
PII: S0378-5173(18)30325-9
Knihovny.cz E-resources
- Keywords
- Bioequivalence study, Biorelevant dissolution, Meloxicam, Omeprazole, Supergeneric product,
- MeSH
- Anti-Inflammatory Agents, Non-Steroidal * administration & dosage chemistry pharmacokinetics MeSH
- Citrates chemistry MeSH
- Chemistry, Pharmaceutical MeSH
- Drug Combinations MeSH
- Cross-Over Studies MeSH
- Hydrogen-Ion Concentration MeSH
- Humans MeSH
- Meloxicam MeSH
- Omeprazole * administration & dosage chemistry pharmacokinetics MeSH
- Excipients chemistry MeSH
- Powders MeSH
- Anti-Ulcer Agents * administration & dosage chemistry pharmacokinetics MeSH
- Therapeutic Equivalency MeSH
- Thiazines * administration & dosage chemistry pharmacokinetics MeSH
- Thiazoles * administration & dosage chemistry pharmacokinetics MeSH
- Capsules MeSH
- Drug Liberation MeSH
- Gelatin chemistry MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial MeSH
- Names of Substances
- Anti-Inflammatory Agents, Non-Steroidal * MeSH
- Citrates MeSH
- Drug Combinations MeSH
- Meloxicam MeSH
- Omeprazole * MeSH
- Excipients MeSH
- Powders MeSH
- Anti-Ulcer Agents * MeSH
- Thiazines * MeSH
- Thiazoles * MeSH
- Capsules MeSH
- trisodium citrate MeSH Browser
- Gelatin MeSH
The purpose of this work was to develop a new supergeneric product Meloxicam/Omeprazole. Such a combination brings a benefit in terms of decreasing side effects for the patients using meloxicam. The new combination is composed of a meloxicam powder blend (MPB) and omeprazole gastro-resistant pellets (OAP) in hard gelatin capsules. The main tasks were to select the excipients to keep the functional layer of OAP active and to prove the bioequivalence to the original products of meloxicam tablets together with omeprazole capsules. Although dissolution profiles similar to the original product were obtained, the unexpected results of omeprazole low bioavailability in the fed bioequivalence study (BES I) showed the necessity to investigate the formulation in greater depth. A modified more complex dissolution method was developed in order to understand the release of omeprazole under gastric conditions. This method revealed the degradation of omeprazole in the formulation when exposed to the fed conditions because of the increase in microenvironmental pH in the capsule caused by trisodium citrate, commonly used for improving solubility of meloxicam. This pH increase dissolved the gastro-resistant layer of OAP and caused the chemical degradation. To prevent this effect, a trisodium citrate-free formulation was developed. Reformulated capsules passed the repeated fed bioequivalence study (BES II).
References provided by Crossref.org
Development of a New Bioequivalent Omeprazole Product