The prevalence of mycotic diseases of the oral cavity has been growing with the increasing frequency of the use of antibiotics, corticosteroids, etc. The most common mycotic diseases of oral cavity mucosa are induced by Candida myco-organisms. Local therapy of oral candidoses is based on the application of antiseptics and antimycotics. At present, there is only one preparation for the local oral administration of antimycotics in the market, which has a form of mucoadhesive tablets. Unlike mucoadhesive tablets, mucoadhesive films provide greater flexibility and many advantages: do not obstruct speech and food and drink intake, application does not cause an unpleasant sensation of a foreign body in the oral cavity, and they cover lesions. The aim of this project is to prepare a new dosage form, oral mucoadhesive film containing a promising oral antimycotics ciclopirox-olamine, and in vitro and in vivo evaluation focusing on the quality parameters of the prepared drug form, its effectiveness and safety.

Prevalence mykotických onemocnění sliznice dutiny ústní narůstá spolu se zvýšenou frekvencí podávání antibiotik, kortikosteroidů a imunosupresiv. Mezi nejčastější mykotická onemocnění sliznice dutiny ústní patří infekce vyvolané mykoorganismy rodu Candida. Lokální terapie orálních kandidóz spočívá v místní aplikaci antiseptických přípravků a antimykotik. V současnosti je na trhu pouze jeden přípravek pro lokální orální podání antimykotika ve formě mukoadhezivní tablety. Oproti mukoadhezivním tabletám nabízí mukoadhezivní filmy vzhledem ke své flexibilitě a tvaru řadu výhod - neomezují mluvení, příjem potravy a tekutin, po jejich aplikaci nevzniká nepříjemný pocit cizího tělesa v dutině ústní, kryjí léze. Předmětem projektu je příprava nové lékové formy, orálního mukoadhezivního filmu s obsahem orálně perspektivního antimykotika ciklopirox-olaminu a in-vitro a in-vivo hodnocení se zaměřením na jakostní parametry připravené lékové formy a na účinnost a bezpečnost léčby.

• MeSH
• antifungální látky aplikace a dávkování   terapeutické užití   MeSH
• antiinfekční látky lokální aplikace a dávkování   terapeutické užití   MeSH
• aplikace orální MeSH
• biofilmy MeSH
• buněčná adheze MeSH
• hodnocení léčiv MeSH
• orální kandidóza farmakoterapie   MeSH
• pyridony aplikace a dávkování   terapeutické užití   MeSH
• systémy cílené aplikace léků MeSH

• Konspekt
• Farmacie. Farmakologie
• NLK Obory
• farmacie a farmakologie
• otorinolaryngologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

BACKGROUND: Prevalence of oral mucosal fungal infections increases with the frequent administration of antibiotics, corticosteroids and immunosuppressive drugs. Therapeutically used antifungals are usually associated with a variety of drug interactions. Furthermore, there has been a noticeable increase in microorganisms resistant to these preparations. Mucoadhesive buccal films represent a modern therapeutic system for the treatment of oral mucosal fungal infection paired with a high degree of patient compliance. Ciclopirox olamine applied directly onto the oral mucosa offers an attractive alternative to treatment with systemic antifungals thanks to its low incidence of resistance and side effects. OBJECTIVE: The aim of this work was to evaluate the pharmacokinetic parameters of ciclopirox olamine after the buccal application of mucoadhesive film prepared by the solvent casting method. METHOD: A chromatographic method using an internal standard was developed and validated for evaluation of ciclopirox olamine plasma concentrations. Method accuracy was 88.5-104.6% and 89.5-99.7% for interday and intraday assays, respectively. RESULTS: The pharmacokinetic properties of ciclopirox olamine were studied in New Zealand White rabbits. The mucoadhesive films containing ciclopirox olamine in a total dose of 34.4 (33.0; 35.9) mg kg-1 were applied to all the rabbits. Plasma ciclopirox olamine concentrations were determined during the 12 h following application. The time taken to reach maximum plasma concentration was 1.7 (1.1; 2.2) h after the drug administration with cmax 5.73 (4.18; 7.28) μg mL-1. Overall elimination half-life was 3.8 (1.9; 10.8) h. CONCLUSION: The experiment suggests that oral mucoadhesive film may be a valuable alternative ciclopirox olamine administration.

• MeSH
• antifungální látky aplikace a dávkování   krev   farmakokinetika   MeSH
• aplikace bukální MeSH
• králíci MeSH
• molekulární struktura MeSH
• pyridony aplikace a dávkování   krev   farmakokinetika   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

CONTEXT: Mucoadhesive oral films, with their prolonged residence time at the site of application, offer a promising approach for protection of the oral lesion surface. The addition of sodium hyaluronate of different molecular weights as a second mucoadhesive polymer into the film matrix could positively influence the physico-mechanical and mucoadhesive properties of films. OBJECTIVE: The aim of this study was to investigate the formulation of a monolayered film matrix containing varying amounts of sodium hyaluronate and to test the properties of such matrices by applying different characterization methods. MATERIALS AND METHODS: Film matrix was composed of two mucoadhesive polymers, carmellose sodium and sodium hyaluronate, plasticized with glycerol. Resulting films were characterized with regard to their viscosity and physico-mechanical properties. RESULTS AND DISCUSSION: Multivariate data analysis was employed to evaluate the influence of varying amounts of mucoadhesive polymers on the main mucoadhesive oral films' properties. The lower content of sodium hyaluronate caused improvements in mechanical properties and residence time on the artificial oral mucosa, both of which are the main characteristics that determine the quality of the final product. CONCLUSIONS: The best results were obtained by samples containing carmellose sodium with a small amount of sodium hyaluronate (about 0.5% in casting dispersion).

• MeSH
• adheziva chemie   metabolismus   MeSH
• adhezivita MeSH
• glycerol chemie   metabolismus   MeSH
• kyselina hyaluronová chemie   metabolismus   MeSH
• lidé MeSH
• multivariační analýza MeSH
• orální absorpce MeSH
• pevnost v tahu MeSH
• polymery MeSH
• sodná sůl karboxymethylcelulosy chemie   metabolismus   MeSH
• systémy cílené aplikace léků metody   MeSH
• ústní sliznice metabolismus   MeSH
• uvolňování léčiv MeSH
• viskozita MeSH
• zvláčňovadla chemie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Cílem tohoto článku je poskytnout přehled o mukoadhezivních lékových formách aplikovaných do dutiny ústní, se zaměřením na inovativní formulace mukoadhezivních filmů z hlediska jejich výhod, složení, přípravy a praktického využití. Filmy složené z mukoadhezivních polymerů připravené některou ze zavedených metod (odpařování rozpouštědla, extruze taveniny atd.) mohou být perspektivními kandidáty pro orální aplikaci řady léčiv, především pro jejich flexibilitu a pohodlnost použití. K dalším výhodám této lékové formy patří prodloužení krátké doby setrvání konvenčních orálních lékových forem na sliznici a podání přesné dávky léčiva na místo aplikace. Kromě toho mohou také překrytím chránit a izolovat povrch slizniční léze, což napomáhá ke snížení bolestivosti a zlepšení účinnosti léčby.

This article aims to provide an overview about mucoadhesive dosage forms applied to the oral cavity, focusing on the innovative formulations of mucoadhesive films in terms of their advantages, composition, preparation and practical use. Films (patches) composed of mucoadhesive polymers prepared by any of the established methods (solvent casting, melt-extrusion, etc.) may be promising candidates for oral administration of many drugs, especially for their flexibility and convenience of use. Other advantages of these formulations include prolongation of a short retention time of conventional oral dosage forms to the mucosa and administration of precise doses of the drug to the application site. In addition, films are able to cover and protect the surface of mucosal lesions, which helps to reduce pain and improve the treatment efficacy.

• MeSH
• aplikace orální MeSH
• biofilmy * MeSH
• buněčná adheze MeSH
• farmaceutická technologie MeSH
• lékové formy MeSH
• lidé MeSH
• povrchové vlastnosti MeSH
• rozpouštědla MeSH
• ústa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Tento článek si klade za cíl podat stručné, ale komplexní informace o dutině ústní jako vhodném místě pro aplikaci léčivého přípravku, a tím i pro přívod léčiva do organizmu. Nespornými výhodami této aplikační cesty je snadná přístupnost, nízká enzymatická aktivita, bohaté prokrvení dané oblasti, možnost eliminace first-pass efektu, zamezení presystémové eliminaci v trávicí soustavě a možnost navození lokálního i systémového účinku léčiva. Článek je první ze série a měl by objasnit základní anatomické a fyziologické poměry v dutině ústní, a tím osvětlit její možnosti a přednosti pro aplikaci léčivého přípravku.

This article aims to provide a brief, but comprehensive overview about the oral cavity as a perspective region for the application of dosage forms and thus the administration of drugs into the body. The main advantages of this application route are: the easy accessibility and low enzymatic activity; rich blood supply of the area; circumventing the first pass effect; avoidance of presystemic elimination within the digestive tract and the possibility of local as well as systemic effect of the drug. The article is first in the series, and is aimed to clarify the basic anatomical and physiological conditions in the oral cavity and thereby discuss the opportunities and advantages for the application of the medicinal product by this route.

• MeSH
• aplikace bukální MeSH
• aplikace orální MeSH
• orální absorpce účinky léků   MeSH
• ústa anatomie a histologie   fyziologie   MeSH
• ústní sliznice MeSH
• způsoby aplikace léků * MeSH
• Publikační typ
• práce podpořená grantem MeSH

• MeSH
• antibakteriální látky aplikace a dávkování   krev   farmakokinetika   MeSH
• injekce intramuskulární veterinární   MeSH
• králíci MeSH
• penicilin G aplikace a dávkování   krev   farmakokinetika   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The aim of the presented research was the preparation and in vitro and in vivo evaluation of mucoadhesive oral films containing nystatin. Multivariate data analysis was used to evaluate an innovative approach, in which a combination of different mucoadhesive polymers was employed. The purpose of this was to assess the effects of such a combination on non-woven insoluble carmellose textile as a drug-release modifier in the structure of the film. It was observed that the mucoadhesive films prepared using polyethylene oxide were more plastic, showed less mechanical resistance and shorter in vitro residence time in comparison with films containing sodium carmellose. The textile used in films containing sodium carmellose significantly prolonged both in vitro and in vivo residence times in rabbits from 50 ± 4 min until 74 ± 4 min and from 48 ± 6 until 80 ± 4 min, respectively. A higher degree of substitution by the acid carboxymethyl group of the textile resulted in slower nystatin dissolution, longer in vitro and in vivo residence times, and higher tensile strength. Textural parameters tensile strength and tensile deformation in conjunction with linear discriminant analysis were able to distinguish the degree of substitution of the textile due to its impact on the studied parameters.

• MeSH
• adhezivita MeSH
• biologická dostupnost MeSH
• experimenty na zvířatech MeSH
• králíci MeSH
• léčivé přípravky MeSH
• nosiče léků chemie   MeSH
• nystatin terapeutické užití   MeSH
• orální kandidóza * farmakoterapie   prevence a kontrola   MeSH
• polymery chemie   terapeutické užití   MeSH
• systémy cílené aplikace léků MeSH
• techniky in vitro MeSH
• textilie MeSH
• ústní sliznice metabolismus   účinky léků   MeSH
• Check Tag
• králíci MeSH
• Publikační typ
• práce podpořená grantem MeSH

Mucoadhesive buccal films (MBFs) provide an innovative way to facilitate the efficient site-specific delivery of active compounds while simultaneously separating the lesions from the environment of the oral cavity. The structural diversity of these complex multicomponent and mostly multiphase systems as well as an experimental strategy for their structural characterization at molecular scale with atomic resolution were demonstrated using MBFs of ciclopirox olamine (CPX) in a poly(ethylene oxide) (PEO) matrix as a case study. A detailed description of each component of the CPX/PEO films was followed by an analysis of the relationships between each component and the physicochemical properties of the MBFs. Two distinct MBFs were identified by solid-state NMR spectroscopy: (i) at low API (active pharmaceutical ingredient) loading, a nanoheterogeneous solid solution of CPX molecularly dispersed in an amorphous PEO matrix was created; and (ii) at high API loading, a pseudoco-crystalline system containing CPX-2-aminoethanol nanocrystals incorporated into the interlamellar space of a crystalline PEO matrix was revealed. These structural differences were found to be closely related to the mechanical and physicochemical properties of the prepared MBFs. At low API loading, the polymer chains of PEO provided sufficient quantities of binding sites to stabilize the CPX that was molecularly dispersed in the highly amorphous semiflexible polymer matrix. Consequently, the resulting MBFs were soft, with low tensile strength, plasticity, and swelling index, supporting rapid drug release. At high CPX content, however, the active compounds and the polymer chains simultaneously cocrystallized, leaving the CPX to form nanocrystals grown directly inside the spherulites of PEO. Interfacial polymer-drug interactions were thus responsible not only for the considerably enhanced plasticity of the system but also for the exclusive crystallization of CPX in the thermodynamically most stable polymorphic form, Form I, which exhibited reduced dissolution kinetics. The bioavailability of CPX olamine formulated as PEO-based MBFs can thus be effectively controlled by inducing the complete dispersion and/or microsegregation and nanocrystallization of CPX olamine in the polymer matrix. Solid-state NMR spectroscopy is an efficient tool for exploring structure-property relationships in these complex pharmaceutical solids.

• MeSH
• adheziva chemie   metabolismus   MeSH
• biologická dostupnost MeSH
• chemie farmaceutická metody   MeSH
• ethylenoxid chemie   MeSH
• krystalizace metody   MeSH
• magnetická rezonanční spektroskopie metody   MeSH
• nanočástice chemie   MeSH
• orální absorpce fyziologie   MeSH
• polyethylenglykoly chemie   metabolismus   MeSH
• polymery chemie   MeSH
• pyridony chemie   MeSH
• rozpustnost MeSH
• ústní sliznice metabolismus   MeSH
• uvolňování léčiv fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Infectious stomatitis represents the most common oral cavity ailments. Current therapy is insufficiently effective because of the short residence time of topical liquid or semisolid medical formulations. An innovative application form based on bioadhesive polymers featuring prolonged residence time on the oral mucosa may be a solution to this challenge. This formulation consists of a mucoadhesive oral film with incorporated nanocomposite biomaterial that is able to release the drug directly at the target area. This study describes the unique approach of preparing mucoadhesive oral films from carmellose with incorporating a nanotechnologically modified clay mineral intercalated with chlorhexidine. The multivariate data analysis was employed to evaluate the influence of the formulation and process variables on the properties of the medical preparation. This evaluation was complemented by testing the antimicrobial and antimycotic activity of prepared films with the aim of finding the most suitable composition for clinical application. Generally, the best results were obtained with sample containing 20 mg of chlorhexidine diacetate carried by vermiculite, with carmellose in the form of nonwoven textile in its structure. In addition to its promising physicomechanical, chemical, and mucoadhesive properties, the formulation inhibited the growth of Staphylococcus and Candida; the effect was prolonged for tens of hours.

• MeSH
• antiinfekční látky aplikace a dávkování   chemie   MeSH
• biokompatibilní materiály aplikace a dávkování   chemie   MeSH
• chemie farmaceutická MeSH
• chitosan chemie   MeSH
• chlorhexidin aplikace a dávkování   chemie   MeSH
• lidé MeSH
• nanokompozity aplikace a dávkování   chemie   MeSH
• polymery aplikace a dávkování   chemie   MeSH
• sodná sůl karboxymethylcelulosy aplikace a dávkování   chemie   MeSH
• stomatitida farmakoterapie   mikrobiologie   MeSH
• systémy cílené aplikace léků * MeSH
• ústa účinky léků   mikrobiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Oral mucosa is an attractive region for the local and systemic application of many drugs. Oral mucoadhesive films are preferred for their prolonged time of residence, the improved bioavailability of the drug they contain, their painless application, their protection against lesions, and their nonirritating properties. This work was focused on preparation of nonmedicated carmellose-based films using both solvent casting and impregnation methods, respectively. Moreover, a modern approach to evaluation of mucoadhesive films applying analysis of texture and subsequent multivariate data analysis was used. In this experiment, puncture strength strongly correlated with tensile strength and could be used to obtain necessary information about the mechanical film characteristics in films prepared using both methods. Puncture work and tensile work were not correlated in films prepared using the solvent casting method, as increasing the amount of glycerol led to an increase in the puncture work in thinner films. All measured texture parameters in films prepared by impregnation were significantly smaller compared to films prepared by solvent casting. Moreover, a relationship between the amount of glycerol and film thickness was observed, and a greater recalculated tensile/puncture strength was needed for an increased thickness in films prepared by impregnation.

• MeSH
• aplikace orální MeSH
• membrány umělé * MeSH
• preklinické hodnocení léčiv MeSH
• systémy cílené aplikace léků metody   MeSH
• testování materiálů * MeSH
• ústní sliznice * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH