Current in vitro drug-release testing of the sustained-release parenterals represents the in vivo situation insufficiently. In this work, a thin agarose hydrogel layer surrounding the tested dosage form was proposed to mimic the tissue. The method was applied on implantable formulations of different geometries (films, microspheres, and cylindrical implants); prepared from various polymers (several Resomer® grades or ethyl cellulose) and loaded with different model drugs: flurbiprofen, lidocaine or risperidone. The hydrogel layer did not possess any retarding effect on the released drug and acted as a physical restriction to swelling and/or plastic deformation of the tested dosage forms. This led to a different surface area available for drug-release compared with testing in release medium alone and correspondingly to significantly different release profiles of the majority of the formulations obtained between the two methods (e.g. t50% = 18 days in pure release medium vs. t50% = 26 days in gel-setup for risperidone loaded Resomer® 503 H films or t50% = 7 days vs. t50% = 19 days for risperidone loaded Resomer® 503 H microspheres). The limited space for swelling and the rigidity of the agarose gel might mimic the tight encapsulation of the dosage form in the tissue better than the conventional liquid medium.
Intracranial epidermoid cysts are slow growing congenital avascular neoplasms that spread across the basal surface of the brain. They most commonly occur in the paramedial region in the cerebellopontine angle and the parasellar region. Despite its generally benign nature, sporadically they can be accompanied with hemorrhage or very rarely undergo malignant transformation. The authors present a case report of a patient with a hemorrhagic vermian epidermoid cyst and a review of all published similar cases.
- Publikační typ
- kazuistiky MeSH
Despite the importance of drug release testing of parenteral depot formulations, the current in vitro methods still require ameliorations in biorelevance. We have investigated here the use of muscle tissue components to better mimic the intramuscular administration. For convenient handling, muscle tissue was used in form of a freeze-dried powder, and a reproducible process of incorporation of tested microspheres to an assembly of muscle tissue of standardized dimensions was successfully developed. Microspheres were prepared from various grades of poly(lactic-co-glycolic acid) (PLGA) or ethyl cellulose, entrapping flurbiprofen, lidocaine, or risperidone. The deposition of microspheres in the muscle tissue or addition of only isolated lipids into the medium accelerated the release rate of all model drugs from microspheres prepared from ester-terminated PLGA grades and ethyl cellulose, however, not from the acid-terminated PLGA grades. The addition of lipids into the release medium increased the solubility of all model drugs; nonetheless, also interactions of the lipids with the polymer matrix (ad- and absorption) might be responsible for the faster drug release. As the in vivo drug release from implants is also often faster than in simple buffers in vitro, these findings suggest that interactions with the tissue lipids may play an important role in these still unexplained observations.
- MeSH
- celulosa analogy a deriváty MeSH
- flurbiprofen aplikace a dávkování MeSH
- kopolymer kyseliny glykolové a mléčné MeSH
- léky s prodlouženým účinkem * MeSH
- lidokain aplikace a dávkování MeSH
- mikrosféry MeSH
- nosiče léků MeSH
- parenterální infuze * MeSH
- pomocné látky MeSH
- prasata MeSH
- příprava léků MeSH
- risperidon aplikace a dávkování MeSH
- svaly metabolismus MeSH
- techniky in vitro MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Concomitant intake of alcoholic beverages with sustained-release oral formulations may potentially lead to dose dumping. Alcohol-resistance testing is currently a requirement for the manufacturers by regulatory authorities. Silk fibroin produced by silkworm Bombyx mori is suggested in this work as a potential alternative to a narrow spectrum of alcohol-resistant excipients. Oxycodone HCl, tramadol HCl, and flurbiprofen were selected as model drugs and formulated with regenerated silk fibroin either in the form of an amorphous solid dispersion or as a physical mixture and compressed into tablets. Preliminary compactability and tampering-resistance studies were performed. The ethanol-resistance was tested in media containing 5%, 10%, 20%, or 40% (v/v) ethanol concentration. Drug release profiles were compared using f2 similarity factor. Good mechanical tampering-resistance (tensile strength of 14.6 MPa at 400 MPa compression pressure) was obtained for tablets compressed from physical mixture. Tablets compressed from amorphous solid dispersion had lower tensile strength (2.2 MPa) but showed chemical tampering-resistance to extraction by pure ethanol (7.1% of oxycodone HCl after 24 h). Drug release is controlled predominantly by swelling and diffusion. With an increasing ethanol concentration in release medium, the tablets swelled less, resulting in a slower release. This trend was similar for all tested drugs and for both physical states formulations. No dose dumping occurred in the presence of ethanol; therefore, silk fibroin could be considered as an alternative alcohol-resistant excipient for sustained release application.
- MeSH
- fibroiny chemie MeSH
- léky s prodlouženým účinkem * MeSH
- pomocné látky * MeSH
- tablety MeSH
- Publikační typ
- časopisecké články MeSH
105 l. : tab. ; 30 cm
- MeSH
- empirický výzkum MeSH
- hluk dopravní prevence a kontrola statistika a číselné údaje MeSH
- motorová vozidla MeSH
- ukazatele zdravotního stavu MeSH
- vystavení vlivu životního prostředí MeSH
- Konspekt
- Životní prostředí a jeho ochrana
- NLK Obory
- environmentální vědy
- pracovní lékařství
- technika
- NLK Publikační typ
- výzkumné zprávy
- MeSH
- doprava MeSH
- hluk dopravní MeSH
