Improvement of the wettability and dissolution of fenofibrate compacts by plasma treatment

The goal of this study was to investigate the effect of plasma treatment on the wettability and dissolution of fenofibrate compacts. Contact angle measurements and intrinsic dissolution rate studies of untreated and plasma-treated fenofibrate compacts were conducted. The contact angle data clearly show that the wettability of the tablet surface increased with the duration of plasma treatment.Analyses of stability revealed that the surfaces which were plasma-treated for more than 1 min regained some degree of hydrophobicity after storage in air. Since their hydrophobic recovery finally reached the level observed with 1 min plasma-treated fenofibrate compacts it was deduced that permanent incorporation of hydrophilic groups had already attained saturation upon plasma irradiation for 1 min.Dissolution studies revealed the advantages of the hydrophilized surface of plasma-treated fenofibrate compacts. Due to the improved wettability of plasma-treated fenofibrate its intrinsic dissolution rate was vastly increased compared to untreated fenofibrate. This study thus demonstrates the potential of plasma treatment to enhance the wettability and dissolution behavior of poorly water-soluble drugs.     

Influences of heat seal lacquer thickness on the quality of blister packages

A sealability of aluminium lidding foils against formable polymer materials of blister packages is usually achieved by a coating of aluminium with certain grammages of heat seal lacquers. To investigate influences of their thickness on quality of blister packages, lidding foils with different grammages of two lacquer types were manufactured. Sealing experiments (variation of temperature, pressure and sealing time) were performed. Sealed seam strengths were determined with mechanical tensile tests, tightness of cold form blisters were analysed by means of helium leakage tests. Time-dependent moisture uptake of stored blisters was monitored with micro-gas chromatography. By means of a simple calculation model the permeability coefficients of the heat seal lacquers were determined. Lidding foils with higher lacquer grammages showed significantly greater sealed seam strengths. Helium leakage tests showed only slight effects of heat seal lacquer grammage on tightness of blisters. But cold form blisters with lidding foils of higher lacquer grammages showed a significantly greater moisture uptake. Since the heat seal lacquers and the rigid polyvinyl chloride of the formable aluminium compound foils had similar permeability coefficients, the contribution of the lacquers to the total permeability of the investigated cold form blisters was only slightly.     

IVIVC in oral absorption for fenofibrate immediate release tablets using a dissolution/permeation system

The usefulness of a dissolution/permeation (D/P) system to predict the in vivo performance of solid dosage forms containing the poorly soluble drug, fenofibrate, was studied. Biorelevant dissolution media simulating the fasted and fed state conditions of the human gastrointestinal tract were used in order to simulate the effect of food on the absorption of fenofibrate. Moreover, the results obtained from the D/P system were correlated with pharmacokinetic parameters obtained following in vivo studies in rats. The in vitro parameter (amount permeated in the D/P system) reflected well the in vivo performance in rats in terms of AUC and C(max) of fenofibric acid. This study thus demonstrates the potential of the D/P system as valuable tool for absorption screening of dosage forms for poorly soluble drugs.     

Left temporal low‐frequency rTMS for the treatment of tinnitus: clinical predictors of treatment outcome – a retrospective study

Background: There is increasing evidence that repetitive transcranial magnetic stimulation (rTMS) can reduce chronic tinnitus. However, treatment results are characterized by high interindividual variability. Therefore, the identification of predictors for treatment response is of high clinical relevance. Methods: Clinical data of 194 patients with tinnitus were evaluated. All patients were treated with a standardized rTMS procedure (1 Hz, 10 days, 2000 stimuli/day, over the left temporal cortex). A potential influence on the outcome was analysed for the following parameters: age, gender, depression scores in Beck Depression Inventory (BDI) and tinnitus severity (TQ) before rTMS, lateralization, frequency and duration of tinnitus and extent of hearing loss. Results: An effect of tinnitus laterality was observed. In patients with left‐sided or bilateral tinnitus, rTMS resulted in a statistically significant reduction of TQ scores, whereas patients with right‐sided tinnitus did not show a significant improvement after rTMS treatment. However, in correlation analyses, we found a trend which did not reach statistical significance that in the subgroup of treatment responders tinnitus duration influenced rTMS outcome. In addition, a multiple regression analysis identified the TQ score at baseline as a significant predictor for treatment outcome. For all other investigated parameters, no statistically significant effects were found. Conclusions: This study suggests that left temporal low‐frequency rTMS has beneficial effects in left‐sided and bilateral tinnitus, but not in right‐sided tinnitus. In line with the results from earlier studies involving smaller samples, tinnitus duration was found to influence rTMS outcome.     

Exercise and psychological well-being

Research on the association between physical activity and mental health addresses the beneficial effects of physical activity on emotional and cognitive functioning. With regard to emotional functioning, most studies focus on the influence of physical activity on depressive symptoms or affective disorders. These studies show that the beneficial effects of aerobic exercise and pharmacotherapy on depressive symptoms seem to be comparable and discuss a variety of neurobiological mechanisms that improve symptoms. The positive effects of physical activity on anxious mood and anxiety disorders are also well documented. Desensitization to physiological changes, improved self-esteem, and self-efficacy seem to play an important part. However, aerobic exercise does not improve mental health in every case, as seen for instance in over-trained athletes. Research on the relationship between physical activity and cognitive functioning reveals that physical activity can prevent the age-related cognitive decline and can delay the onset of dementia. Physical activity has beneficial effects not only on adults but also on children's and adolescents' mental health and cognitive performance, particularly on their executive functions that are still developing throughout adolescence. Finally, physical activity also affects the endocrine stress-regulation system: trained people reveal stronger reactivity and quicker regeneration when faced with stressful events.     

Enriched cereal bars are more effective in increasing plasma quercetin compared with quercetin from powder-filled hard capsules

The flavonol quercetin, is one of the major flavonoids found in edible plants. The bioavailability of quercetin in humans may be influenced by the food matrix in which it is consumed as well as by its chemical and physical form. The objective of the present study was to investigate the biokinetics of quercetin from quercetin-enriched cereal bars and quercetin powder-filled hard capsules. In a randomised, single-blinded, diet-controlled cross-over study, six healthy women aged 22-28 years took a single oral dose of approximately 130?mg quercetin equivalents from either quercetin-enriched cereal bars (containing 93·3?% quercetin aglycone plus 6·7?% quercetin-4'-glucoside) or quercetin powder-filled hard capsules (100?% quercetin aglycone). Blood samples were drawn before and after quercetin administration over a 24?h period. The concentrations of quercetin and its monomethylated derivatives, isorhamnetin (3'-O-methyl quercetin) and tamarixetin (4'-O-methyl quercetin), were measured by HPLC with fluorescence detection after plasma enzymatic treatment. The systemic availability as determined by comparing the plasma concentration-time curves of quercetin was found to be five times and the cmax values six times higher after ingestion of 130?mg quercetin by quercetin-enriched cereal bars than after ingestion by quercetin capsules. In contrast, tmax did not differ significantly between the two treatments. The cmax values for isorhamnetin and tamarixetin were four and nine times higher after ingestion of quercetin by quercetin-enriched cereal bars than after ingestion by quercetin capsules. In conclusion, quercetin from quercetin-enriched cereal bars is significantly more bioavailable than from quercetin powder-filled hard capsules.     

Pharmacokinetics of atenolol and metoprolol administered together with piroxicam

A possible pharmacokinetic interaction of atenolol or metoprolol and piroxicam was investigated over a period of 7 days. The mean plasma concentration versus time curve of atenolol (n=6) was nearly uninfluenced, whereas the mean metoprolol concentrations (n=6) were enhanced (statistically not significant). The pharmacokinetic parameters of both atenolol and metoprolol obtained from the plasma concentrations and urinary excretion on the 7. day of treatment were not significantly changed.