Background/Objectives: Omeprazole undergoes degradation in acidic conditions, which makes it unstable in low pHs found in the gastric environment. The vast majority of already marketed omeprazole formulations use enteric polymer coatings to protect the drug from exposure to acidic pH in the stomach, allowing for drug release in the small intestine where the pH is higher. This study aimed to explore the technical aspects of using stomach acid neutralizers as an alternative to polymeric coatings for omeprazole. Methods: After evaluating various neutralizers, magnesium oxide and sodium bicarbonate were chosen to be incorporated into capsules containing omeprazole, which then underwent in vitro dissolution testing to assess their ability to maintain optimal pH levels and ensure appropriate dissolution kinetics. Hygroscopicity and chemical stability of the selected formulation were tested to prove pharmaceutical quality of the product. An in vivo pharmacokinetic study was conducted to demonstrate the efficacy of the omeprazole-sodium bicarbonate formulation in providing faster absorption in humans. Results: Sodium bicarbonate was selected as the most suitable antacid for ensuring omeprazole stabilization. Its quantity was optimized to effectively neutralize stomach acid, facilitating the rapid release and absorption of omeprazole. In vitro studies demonstrated the ability of the formulation to neutralize gastric acid within five minutes. In vivo studies indicated that maximum concentrations of omeprazole were achieved within half an hour. The product met the requirements of pharmaceutical quality. Conclusions: An easily manufacturable, fast-absorbing oral formulation was developed as an alternative to enteric-coated omeprazole.
- Klíčová slova
- absorption, drug release, neutralization, omeprazole, pharmacokinetics, stability,
- Publikační typ
- časopisecké články 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).
- Klíčová slova
- Bioequivalence study, Biorelevant dissolution, Meloxicam, Omeprazole, Supergeneric product,
- MeSH
- antiflogistika nesteroidní * aplikace a dávkování chemie farmakokinetika MeSH
- citráty chemie MeSH
- farmaceutická chemie MeSH
- fixní kombinace léků MeSH
- klinické křížové studie MeSH
- koncentrace vodíkových iontů MeSH
- lidé MeSH
- meloxikam MeSH
- omeprazol * aplikace a dávkování chemie farmakokinetika MeSH
- pomocné látky chemie MeSH
- prášky, zásypy, pudry MeSH
- protivředové látky * aplikace a dávkování chemie farmakokinetika MeSH
- terapeutická ekvivalence MeSH
- thiaziny * aplikace a dávkování chemie farmakokinetika MeSH
- thiazoly * aplikace a dávkování chemie farmakokinetika MeSH
- tobolky MeSH
- uvolňování léčiv MeSH
- želatina chemie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- Názvy látek
- antiflogistika nesteroidní * MeSH
- citráty MeSH
- fixní kombinace léků MeSH
- meloxikam MeSH
- omeprazol * MeSH
- pomocné látky MeSH
- prášky, zásypy, pudry MeSH
- protivředové látky * MeSH
- thiaziny * MeSH
- thiazoly * MeSH
- tobolky MeSH
- trisodium citrate MeSH Prohlížeč
- želatina MeSH
In recent years there has been a growing interest in formulating solid dispersions, which purposes mainly include solubility enhancement, sustained drug release and taste masking. The most notable problem by these dispersions is drug-carrier (in)solubility. Here we focus on solubility parameters as a tool for predicting the solubility of a drug in certain carriers. Solubility parameters were determined in two different ways: solely by using calculation methods, and by experimental approaches. Six different calculation methods were applied in order to calculate the solubility parameters of the drug ibuprofen and several excipients. However, we were not able to do so in the case of ibuprofen lysinate, as calculation models for salts are still not defined. Therefore, the extended Hansen's approach and inverse gas chromatography (IGC) were used for evaluating of solubility parameters for ibuprofen lysinate. The obtained values of the total solubility parameter did not differ much between the two methods: by the extended Hansen's approach it was δt = 31.15 MPa(0.5) and with IGC it was δt = 35.17 MPa(0.5). However, the values of partial solubility parameters, i.e., δd, δp and δh, did differ from each other, what might be due to the complex behaviour of a salt in the presence of various solvents.
- Klíčová slova
- Hansen’s solubility parameters, extended Hansen’s approach, ibuprofen, ibuprofen lysinate, inverse gas chromatography,
- MeSH
- antiflogistika nesteroidní chemie MeSH
- chromatografie plynová MeSH
- farmaceutická technologie metody MeSH
- ibuprofen analogy a deriváty chemie MeSH
- lysin analogy a deriváty chemie MeSH
- nosiče léků MeSH
- pomocné látky chemie MeSH
- rozpouštědla chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antiflogistika nesteroidní MeSH
- ibuprofen MeSH
- lysin MeSH
- nosiče léků MeSH
- pomocné látky MeSH
- rozpouštědla MeSH
- solufenum MeSH Prohlížeč
