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

Unknown impurities were identified in ibuprofen (IBU) soft gelatin capsules (SGCs) during long-term stability testing by a UHPLC method with UV detection and its chemical formula was determined using high resolution/accurate mass (HRAM) LC-MS. Reference standards of the impurities were subsequently synthesized, isolated by semi-preparative HPLC and characterized using HRAM LC-MS, NMR and IR. Two impurities were formed by esterification of IBU with polyethylene glycol (PEG), which is used as a fill of the SGCs, and were identified as IBU-PEG monoester and IBU-PEG diester. Two other degradants arised from reaction of IBU with sorbitol and sorbitan, which are components of the shell and serves as plasticizers. Thus, IBU sorbitol monoester (IBU-sorbitol) and IBU sorbitan monoester (IBU-sorbitan ester) were identified. An UHPLC method was further optimized in order to separate, selectively detect and quantify the degradation products in IBU SGCs.

• MeSH
• esterifikace MeSH
• ibuprofen analýza   chemie   izolace a purifikace   MeSH
• polysorbáty MeSH
• referenční standardy MeSH
• sorbitol MeSH
• stabilita léku MeSH
• tobolky MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• želatina MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ibuprofen MeSH
• polysorbáty MeSH
• sorbitol MeSH
• tobolky MeSH
• želatina MeSH

OBJECTIVES: A wide range of low-molecular-weight agents can cause occupational asthma. The chemical industry is an environment in which numerous hazardous substances are used. Lasamide (2,4-dichloro-5-sulfamoylbenzoic acid) is one of them (along with its precursors). METHODS: Five patients from a lasamide production line with suspected occupational asthma and rhinitis were examined. During the first visit, skin prick tests, total immunoglobulin E (IgE), a nonspecific bronchoprovocation test, and specific bronchoprovocation tests using occupational agents were performed to confirm the diagnosis of allergic diseases. During the follow-up visit (1-3 years after removal from exposure), all of the tests (except the specific bronchoprovocation test) were performed again. RESULTS: At the first hospitalization, the total IgE levels were increased in three patients. In addition, skin prick tests and the nonspecific bronchoprovocation test were positive for three patients. After the specific bronchoprovocation test, serious bronchoconstriction occurred in three patients; symptoms of rhinitis were present in all five patients. Several years after removal from exposure to the occupational agents, normalization (with respect to the parameters followed) was not yet complete for all of the patients. CONCLUSIONS: The process of lasamide production seems to be hazardous and is likely to cause allergic respiratory disease. The prognosis of allergic diseases caused by these products is not very favorable. Allergic symptoms (despite the removal from occupational allergen exposure) persisted even after several years.

• MeSH
• benzoáty škodlivé účinky   MeSH
• bronchiální astma chemicky indukované   MeSH
• bronchoprovokační testy MeSH
• celoroční alergická rýma chemicky indukované   MeSH
• dospělí MeSH
• imunoglobulin E krev   MeSH
• kožní testy MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci z povolání chemicky indukované   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 2,4-dichloro-5-sulfamoylbenzoic acid MeSH Prohlížeč
• benzoáty MeSH
• imunoglobulin E MeSH