Bilayer mucoadhesive buccal films with prolonged release of ciclopirox olamine for the treatment of oral candidiasis: In vitro development, ex vivo permeation testing, pharmacokinetic and efficacy study in rabbits.

The incidence of fungal infections has increased in recent decades not only in patients with predisposing and risk factors, but it has also spread up due to the widespread use of broad-spectrum antibiotics, immunosuppressants and corticosteroids. A limited number of drugs are currently used to treat oral candidiasis (OC). There is an emerging need to look for new antifungals, to rework or to explore the already known molecules. Ciclopirox olamine (CPX), a broad-spectrum antifungal agent, is currently used for topical dermatologic treatment. In this study, bilayer mucoadhesive buccal films (MBFs) containing poly(ethylene oxide) (PEO) and Eudragit® NM 30D (EU) with the prolonged release of ciclopirox olamine, were developed for the treatment of oral candidiasis. During ex vivo testing it was found that CPX does not pass through the porcine buccal tissue but it accumulates in it, which may be beneficial for the treatment of candidiasis in the oral cavity. In a pharmacokinetic study, the drug release from mucoadhesive films was prolonged with the maximum plasma concentration at 3.4 (1.4; 5.5) h. All rabbits with stomatitis showed progressive healing after the treatment with CPX bilayer mucoadhesive buccal films without organ pathologies.

Preparation and evaluation of carriers for detection of cholinesterase inhibitors.

OBJECTIVES: The aim of the study was to use methods of pharmaceutical technology, and prepare carriers in the form of pellets suitable as a filling of detection tubes for enzymatic detection of cholinesterase inhibitors. The enzymatic detection was based on enzymatic hydrolysis of acetylthiocholine iodide and the subsequent colour reaction of its hydrolysis product with Ellman's reagent. The suitable carriers should be in the form of white, regular and sufficiently mechanically resistant particles of about 1 mm allowing it to capture the enzyme during the impregnation process and ensuring its high activity for enzymatic detection. METHODS: Carriers consisting of microcrystalline cellulose, lactose, povidone, and sodium carboxymethyl cellulose were prepared using extrusion-spheronization method under three different drying conditions in either a hot air oven or a microwave oven. Subsequently, the carriers were impregnated with acetylcholinesterase and their size, shape, mechanical resistance, bulk, tapped and pycnometric density, Hausner ratio, intraparticular and total tapped porosity, and activity were measured and recorded. RESULTS: In this procedure, carriers with different physical parameters and different acetylcholinesterase activity were evaluated. It was found that higher acetylcholinesterase activity was associated not only with a higher intraparticular porosity but also with more regular particles characterized by high sphericity and low total tapped porosity. CONCLUSION: This unique finding is important for the preparation of detection tubes based on enzymatic detection which is still irreplaceable especially in the field of detection and analysis of super-toxic cholinesterase inhibitors.

Comparison in vitro felodipine release rate from the original versus generic product with controlled release of the drug.

After patent protection of original brand is over, there are a lot of generic products occurring on the pharmaceutical market. It may be the way to reduce the price, but on the other hand, one should expect the same quality and almost identity with original brand, because the development of generic drugs is based on pharmacological properties of the original brand. The aim of this study was to compare the similarity of two products with controlled release of felodipine--generic product Presid and original brand Plendil--which are commercially available in Czech Republic, based on in vitro dissolution testing. The dissolution test in three dissolution media of increasing pH (1.2, 4.5, and 6.5) for the simulation of physiological pH within the gastrointestinal tract confirmed controlled release of felodipine from the original product Plendil ER 5 mg and Plendil ER 10 mg during the period of 24 hours. The release of felodipine from generic products Presid 5 mg and Presid 10 mg was not controlled for 24 hours as it is indicated in the information leaflet. In the generic products, felodipine release was controlled just for 12 or 18 hours and in this respect did not show similarity with the original brand. Since patients take the drug just once a day in the morning, the controlled release of felodipine, which lasts only 12 to 18 hours, can cause insufficient blood pressure control especially in the most critical morning hours and higher cardiovascular risk.