ABSTRACT
Abstract Insomnia is becoming increasingly prevalent in the world general population. Therapies used by patients include over-the-counter therapies, herbal and dietary supplements, and pharmacological or nonpharmacological treatments. Among these, zolpidem is a pharmacological treatment popularly used for insomnia. Zolpidem is well tolerated and especially efficacious for initiation of sleep, and therefore is effective for the treatment of sleep-onset insomnia. The purpose of the present study was to design and evaluate zolpidem nanoparticle-impregnated buccal films to prolong the duration of its action. Zolpidem nanospheres were prepared by double emulsion solvent evaporation and then loaded into buccoadhesive films (Z1-Z4) comprised of different concentrations of HPMC K100, Eudragit® RL 100, and carbopol 974P. The prepared films were characterized for physicomechanical properties, mucoadhesion, percent hydration, in vitro drug release, ex vivo permeation, and in vivo studies. In vitro drug release was found to depend upon film composition. Ex vivo studies showed that film Z4 had the highest flux. In vivo studies revealed that administration of zolpidem nanosphere-impregnated film enhanced absorption of the drug (p < 0.0001), with a higher peak plasma concentration (52.54 ± 8.22 ng/mL) and area under the curve from time 0 to α (236.00 ± 39.51 ng.h/mL) than oral administration. The increase in time taken to reach the maximum drug concentration (1.5 h) further signifies the potential of these films to provide prolonged drug release. Given these promising results, we concluded that these buccal films could be an alternative route for effective zolpidem delivery.
Subject(s)
Animals , Male , Pyridines/administration & dosage , Acrylic Resins/administration & dosage , Drug Delivery Systems/methods , Nanospheres/administration & dosage , Hypnotics and Sedatives/administration & dosage , Pyridines/pharmacokinetics , Rabbits , Reference Values , Time Factors , Acrylic Resins/pharmacokinetics , Water/chemistry , Biological Availability , Microscopy, Electron, Scanning , Administration, Oral , Reproducibility of Results , Treatment Outcome , Zolpidem , Hypnotics and Sedatives/pharmacokinetics , Sleep Initiation and Maintenance Disorders/drug therapyABSTRACT
OBJECTIVES: The aim of this study was to test the efficacy of a locally applied 8.5 percent nanostructured doxycycline (DOX) gel in preventing alveolar bone loss in experimental periodontal disease (EPD) in rats by using the tapping mode atomic force microscopy (AFM). MATERIAL AND METHODS: EPD was induced in 24 Wistar rats. Animals were treated with the doxycycline gel topically, immediately after EPD induction, and 3 times a day during 11 days. Four groups (n=6) were formed as follows: Naïve group (animals not subjected to EPD nor treated); non-treated (NT) group (animals subjected to EPD, but not treated); vehicle gel (VG) group (animals subjected to EPD and treated with topical gel vehicle); and DOX group (test group): animals subjected to EPD and treated with the 8.5 percent DOX gel. In order to investigate topographical changes in histological sections, a novel simple method was used for sample preparation, by etching sections from paraffin-embedded specimens with xylol. RESULTS: Comparing the AFM images, several grooves were observed on the surface of the alveolar bone and other periodontal structures in the NT and VG groups, with significantly greater depths when compared to the DOX group (p<0.05). CONCLUSIONS: Periodontal structures were brought into high relief confirming to be a simple and cost-effective method for AFM imaging with ultrastructural resolution. The doxycycline gel was able to afford periodontal surface preservation, with flatter grooves.