In vitro and in vivo evaluation of nano-based films for buccal delivery of zolpidem

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.

Related factors to atazanavir plasma levels in a cohort of HIV positive individuals with undetectable viral load

OBJECTIVE: To evaluate the factors associated with plasma concentrations of atazanavir (ATV) in a cohort of well-controlled HIV infected subjects (undetectable viremia). Design: Cross-sectional study where 69 subjects were consecutively enrolled between April and November, 2011. METHODS: Patients had to be on atazanavir for at least six months, undetectable viral load for a period equal to or longer than 12 months, T CD4+ lymphocyte count higher than 200 cells/mm³, and aged between 18 years and 70 years old. Exclusion criteria were pregnancy, any neurologic disease, active opportunistic disease, hepatitis or cancer. Atazanavir plasma levels were measured by ultra-performance liquid chromatography. RESULTS AND DISCUSSION: Overall, 54 patients (mean age of 47 years and 50% women) were included in the analysis. Those without ritonavir (unboosted atazanavir) had statistically lower plasma concentrations than those with ritonavir boosted atazanavir (p = 0.001) and total and indirect bilirubin were statistically associated with plasma concentration of atazanavir (r = 0.32 and r = 0.33 respectively; p < 0.05 in both cases). no statistical association was found among gender, ethnicity, age, weight, body mass index (BMI), lipid profile, and the plasma concentration of atazanavir. CONCLUSION: in summary, as expected, concomitant ritonavir use was the only factor associated with atazanavir plasma levels. prospective studies with a larger sample size might help to observe an association of atazanavir concentrations to other characteristics such as body weight, since the p-value showed to be close to significance (p = 0.068).