Jan Štembírek

Determination of dependencies among in vitro and in vivo properties of prepared mucoadhesive buccal films using multivariate data analysis

Mucoadhesive films represent the most developed medical form of buccal application. Despite the intense focus on buccal film-based systems, there are no standardized methods for their evaluation, which limits the possibility of comparison of obtained data and evaluation of the significance of influence of formulation and process variables on properties of resulting films. The used principal component analysis, together with a partial least squares regression provided a unique insight into the effects of in vitro parameters of mucoadhesive buccal films on their in vivo properties and into interdependencies among the studied variables. In the present study eight various mucoadhesive buccal films based on mucoadhesive polymers (carmellose, polyethylene oxide) were prepared using a solvent casting method or a method of impregnation, respectively. An ethylcellulose or hydrophobic blend of white beeswax and white petrolatum were used as a backing layer. The addition of polyethylene oxide prolonged the in vivo film residence time (from 53.24±5.38-74.18±5.13 min to 71.05±3.15-98.12±1.75 min), and even more when combined with an ethylcellulose backing layer (98.12±1.75 min) and also improved the films appearance. Tested non-woven textile shortened the in vivo film residence time (from 74.18±5.13-98.12±1.75 min to 53.24±5.38-81.00±8.47 min) and generally worsened the films appearance. Mucoadhesive buccal films with a hydrophobic backing layer were associated with increased frequency of adverse effects.

Carmellose Mucoadhesive Oral Films Containing Vermiculite/Chlorhexidine Nanocomposites as Innovative Biomaterials for Treatment of Oral Infections

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.

The development and in vivo evaluation of a colon drug delivery system using human volunteers

The aim of this study was to develop a multiple-unit dosage system that released model drug into the colon, and also to evaluate the efficiency of the dosage form in human volunteers. The developed system combines pH-, time- and biodegradable polymer-based mechanisms for drug targeting to the colon. Pellet cores containing caffeine as model drug and chitosan and microcrystalline cellulose as excipients were prepared by the extrusion/spheronization method. The prepared pellets were film coated with a pH-dependent polymer, Eudragit FS 30 D. The coating total weight gain was 28.83% (w/w). Thanks to the application of an outer enteric film and the multiple unit design of the dosage form, the variability in gastric emptying was overcome, and a colon-specific targeting relied on the reproducibility of a small intestinal transit time, which was reported to be 3 ± 1 hours. A biodegradable polymer in the pellet core, chitosan, ensured the site-specific release of the model drug due to its solubility at the lower pH of the colonic region and by its biodegradability from the bacteria present. The efficiency of the system was confirmed by the in vivo testing of human saliva. The time of the first appearance of caffeine into the saliva, Tlag, was used as a parameter to estimate the disintegration time of the pellets into the gastrointestinal tract. The caffeine appeared in the saliva within 6.95 ± 1.12 hours (Tlag) in 9 volunteers. A comparison of the reported colon arrival times indicates that the developed system is applicable to colonic drug delivery.