Kinder psychisch kranker Eltern: Winterthurer Studie : wissenschaftlicher Bericht

Das Thema der psychischen Behinderung, der psychischen Invalidisierung und der gesellschaftlichen Folgen dieser Invalidisierung für die Sozialversicherungen begleitet uns bereits seit einigen Jahren. Viel weniger interessiert sich aber die breite Öffentlichkeit für die Frage, was eine psychische Erkrankung von Eltern für deren minderjährige Kinder bedeutet. Umso wichtiger schien es uns, detaillierte und verlässliche Zahlen zu liefern, die die Situation dieser Familien aufzeigen und der Frage nachgehen, wie es mit der Unterstützungssituation aussieht

Elemente einer Transition der beruflichen Vorsorge vom Zwangssparen zu einer Sozialversicherung

ISSN:1662-351

Coupling ultra high-pressure liquid chromatography with mass spectrometry: Constraints and possible applications

The introduction of columns packed with porous sub-2m particles and the extension of the upper pressure limit of HPLC instrumentation to 1300 bar (ultra-high pressure liquid chromatography, UHPLC)has opened new frontiers in resolution and speed of analysis. However, certain constraints appear when coupling UHPLC technology with mass spectrometry (MS). First, the most significant limitation is related to the narrow peaks that are produced by UHPLC that require a fast duty cycle, which is only available on the latest generations of MS devices. Thus, certain analyzers are more readily compatible with UHPLC (e.g., QqQ or TOF/MS) than others (e.g., ion trap or FT-MS). Second, due to the reduction of the column volume, extra-column band broadening can become significant, leading to a reduction in the kinetic performance of the UHPLC–MS configuration. Third, as the mobile phase linear velocity is higher in UHPLC, the electrospray ionization source must also be able to provide high sensitivity at flow rates of up to 1 mL/min. Despite these limitations, the UHPLC–MS/MS platform has successfully been employed over the last decade for various types of applications, including those related to bioanalysis, drug metabolism, multi-residue screening, metabolomics, biopharmaceuticals and polar compounds

Strategies for formulating and delivering poorly water-soluble drugs

Water solubility is a key parameter in drug formulation since it highly influences drug pharmacokinetics and pharmacodynamics. In the past decades, the challenge with poorly water soluble drugs has been growing continuously. As a matter of fact, poorly soluble compounds represent 40% of the top 200 oral drugs marketed in the US, 33% of drugs listed in the US Pharmacopeia, 75% of compounds under development and 90% of new chemical entities. The present article presents and discusses the pharmaceutical strategies available to overcome poor water solubility in light of final drug product examples. First, chemical modifications based on the adjustment of the pH and the design of prodrugs are presented and discussed. Physical modifications based on modified solid states of the drug, small drug particles, cosolvents, surfactants, lipids and cyclodextrins are discussed in a second part. Finally, the option of modifying the route of administration is briefly presented

In vivo distribution and ex vivo permeation of cyclosporine A prodrug aqueous formulations for ocular application

Cyclosporine A is a poorly water-soluble, immunosuppressive drug used to treat a variety of ocular diseases. Its limited solubility makes challenging the development of a cyclosporine A-based eye drop for ocular topical application. Based on the prodrug strategy, the practically insoluble cyclosporine A was converted into a freely soluble prodrug. Such a water-soluble prodrug made it possible to develop water-based concentrated eye drops. The prodrug formulations were tested for their ex vivo permeation and in vivo distribution at three concentrations (equivalent to 0.05%, 0.50% and 2.00% w/v cyclosporine A). The ex vivo permeation experiments were performed on corneal and conjunctival epithelia. The in vivo distribution evaluated the total cyclosporine A present in the ocular structures as well as in serum, spleen and cervical lymphatic ganglions. Each prodrug formulation was compared to conventionally used cyclosporine A eye drops at an equivalent concentration. The experimental results showed that the tested eye drops behaved differently. The prodrug formulation was characterized by the following: i) preferential conjunctival penetration, ii) an interesting capacity to create large tissue deposits and iii) a lower risk of systemic complications and immunosuppression. The prodrug aqueous eye drop was demonstrated to be a patient-friendly option for the treatment of ocular diseases requiring high ocular levels of cyclosporine A, pushing the boundaries of the current therapeutic arsenal

New prostaglandin analog formulation for glaucoma treatment containing cyclodextrins for improved stability, solubility and ocular tolerance

Latanoprost is a practically insoluble prostaglandin F2α analog considered a first-line agent for glaucoma treatment. From a pharmaceutical point of view, latanoprost is challenging to be formulated as an eye drop due to its poor water solubility and the presence of an ester bond that needs to be cleaved in vivo but maintained unchanged during storage. Cyclodextrins (CDs) are known to form complexes with hydrophobic drugs, influencing their stability, availability, solubility, and tolerance in a non-predictable manner. A variety of CDs including native α, β, and γCDs as well as substituted hydroxypropylβCD, hydroxypropylγCD, dimethylβCD, sulphatedβCD, and propylaminoβCD were screened and the most appropriate CD for the formulation of latanoprost for an ocular topical application was selected. Among the tested CDs, propylaminoβCD had the best trade-off between latanoprost stability and availability, which was confirmed by its complex constant value of 3129 M−1. Phase-solubility and NMR investigations demonstrated that the propylaminoβCD effectively formed a complex involving the ester group of latanoprost providing protection to its ester bond, while ensuring proper latanoprost solubilization. Furthermore, in vivo experiments demonstrated that the latanoprost-propylaminoβCD formulation led to lower ocular irritation than the commercial latanoprost formulation used as a reference. The latanoprost-propylaminoβCD formulation was demonstrated to successfully address the main stability, solubility, and tolerance limitations of topical ocular latanoprost therapy for glaucoma