Tuberculosis chemotherapy: current drug delivery approaches

Tuberculosis is a leading killer of young adults worldwide and the global scourge of multi-drug resistant tuberculosis is reaching epidemic proportions. It is endemic in most developing countries and resurgent in developed and developing countries with high rates of human immunodeficiency virus infection. This article reviews the current situation in terms of drug delivery approaches for tuberculosis chemotherapy. A number of novel implant-, microparticulate-, and various other carrier-based drug delivery systems incorporating the principal anti-tuberculosis agents have been fabricated that either target the site of tuberculosis infection or reduce the dosing frequency with the aim of improving patient outcomes. These developments in drug delivery represent attractive options with significant merit, however, there is a requisite to manufacture an oral system, which directly addresses issues of unacceptable rifampicin bioavailability in fixed-dose combinations. This is fostered by the need to deliver medications to patients more efficiently and with fewer side effects, especially in developing countries. The fabrication of a polymeric once-daily oral multiparticulate fixed-dose combination of the principal anti-tuberculosis drugs, which attains segregated delivery of rifampicin and isoniazid for improved rifampicin bioavailability, could be a step in the right direction in addressing issues of treatment failure due to patient non-compliance

Anion-induced water flux as drug release mechanism through cationic Eudragit RS 30D film coatings

The objective of this study was to investigate the anion-controlled drug release mechanism through the cationic coating polymer Eudragit RS 30 D as a function of the anion attraction toward the polymer’s quarternary ammonium group (QAG), anion valence, and film composition. The mechanism was investigated by dissolution testing, determination of chloride ion exchange using ion chromatography, plasticizer leaching by means of differential scanning calorimetry, and water uptake by Karl Fischer titration. All experiments were performed on coated theophylline micro tablets or isolated films of various compositions using 0.01 M sodium nitrate, sodium sulfate, disodium succinate, sodium acetate, and succinic acid as dissolution media. The mechanism of drug release involved an immediate penetration of dissolution medium into the polymer followed by an instant exchange of chloride against the medium’s anion species at completely different rates compared with the drug release. Dependent on the attraction of the anion toward the QAGs, a water flux was induced by back and forth exchanging anions. Strong attraction (nitrate, sulfate) resulted in a low water flux while weak attraction resulted in a high flux (acetate, succinic acid). The water flux increased at increasing number of QAGs. Plasticizer acted as a diluent in respect of the number of QAGs, thus higher plasticizer concentrations led to lower drug release

Effects of vehicle and region of application on absorption of hydrocortisone through canine skin

Objective-To determine the effects of various vehicles on the penetration and retention of hydrocortisone applied to canine skin. Sample Population-20 canine skin samples obtained from the thorax, neck, and groin regions of 5 Greyhounds. Procedure-Skin was harvested from dogs after euthanasia and stored at -20 degrees C until required. The skin was then defrosted and placed into diffusion cells, which were maintained at approximately 32 degrees C by a water bath. Saturated solutions of hydrocortisone that contained trace amounts of radiolabelled [C-14]-hydrocortisone in each vehicle (ie, PBS solution [PBSS] alone, 50% ethanol [EtOH] in PBSS [wt/wt], and 50% propylene glycol in PBSS [wt/wt]) were applied to the outer (stratum corneum) surface of each skin sample, and aliquots of receptor fluid were collected for 24 hours and analyzed for hydrocortisone. Results-The maximum flux of hydrocortisone was significantly higher for all sites when dissolved in a vehicle containing 50% EtOH, compared with PBSS alone or 50% propylene glycol, with differences more prominent in skin from the neck region. In contrast, higher residues of hydrocortisone were found remaining within the skin when PBSS alone was used as a vehicle, particularly in skin from the thorax and neck. Conclusions and Clinical Relevance-Penetration of topically applied hydrocortisone is enhanced when EtOH is used in vehicle formulation. Significant regional differences (ie, among the thorax, neck, and groin areas) are also found in the transdermal penetration and skin retention of hydrocortisone. Variability in clinical response to hydrocortisone can be expected in relation to formulation design and site of application

Promoting healthy outcomes among youth with multiple risks: Innovative approaches

Adolescent behavior problems such as substance use, antisocial behavior problems, and mental health problems have extremely high social costs and lead to overburdened mental health and juvenile justice systems in the United States and Europe. The prevalence of these problems is substantial, and at-risk youth often present with a combination of concerns. An understanding of risk and protective factors at multiple levels, including the child, family, peer, school, and community, has influenced intervention development. At the individual and family levels, the most effective and cost-effective programs work intensively with youth and their families or use individual and group cognitive-behavioral approaches. However, there is a paucity of careful studies of effective policies and programs in the juvenile justice system. Research is needed that focuses on adoption, financing, implementation, and sustainable use of evidence-based programs in public service systems. In addition, the field needs to understand better for whom current programs are most effective to create the next generation of more effective and efficient programs