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Currently, a wide variety of complex non-oral dosage forms are entering the global healthcare market. Although many assays have been described in recent research, harmonized procedures and standards for testing their in vitro performance remain widely unexplored. Among others, dialysis-based techniques such as the Pharma Test Dispersion Releaser are developed for testing the release of drugs from nanoparticles, liposomes, or extracellular vesicle preparations. Here, we provide advanced strategies and practical advice for the development and validation of dialysis-based techniques, including documentation, analysis, and interpretation of the raw data. For this purpose, key parameters of the release assay, including the hydrodynamics in the device at different stirring rates, the selectivity for particles and molecules, as well as the effect of excipients on drug permeation were investigated. At the highest stirring rate, a more than twofold increase in the membrane permeation rate (from 0.99 × 10−3 to 2.17 × 10−3 cm2/h) was observed. Additionally, we designed a novel computer model to identify important quality parameters of the dialysis experiment and to calculate error-corrected release profiles. Two hydrophilic creams of diclofenac, Voltaren® Emulgel, and Olfen® gel, were tested and provide first-hand evidence of the robustness of the assay in the presence of semisolid dosage forms.
In den vergangenen Jahren wurden zahlreiche Stoffe als Photosensibilisatoren evaluiert, deren photodynamische Aktivität gegenüber den Pioniersubstanzen deutlich verbessert werden konnte. Vielen dieser Moleküle blieb jedoch aufgrund ihrer ungünstigen physikochemischen Eigenschaften oder der auftretenden Toxizität die Marktreife versagt. Nanopartikuläre Trägersysteme sind geeignet, Verträglichkeit und Effektivität der Photodynamischen Therapie zu verbessern sowie die Selektivität bei der Behandlung bestimmter Tumorspezies deutlich zu erhöhen. Um dieses Prinzip auf verschiedene Photosensibilisatoren anwenden zu können, wurden in der vorliegenden Arbeit Nanopartikel aus humanem Serumalbumin (HSA) durch Desolvatation hergestellt und die adsorptive, die inkorporative sowie die kovalente Bindung an das Trägersystem untersucht. ...
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease of the hair follicles leading to painful lesions, associated with increased levels of pro-inflammatory cytokines. Numerous guidelines recommend antibiotics like clindamycin and rifampicin in combination, as first-line systemic therapy in moderate-to-severe forms of inflammation. HS has been proposed to be mainly an auto-inflammatory disease associated with but not initially provoked by bacteria. Therefore, it has to be assumed that the pro-inflammatory milieu previously observed in HS skin is not solely dampened by the bacteriostatic inhibition of DNA-dependent RNA polymerase. To further clarify the mechanism of anti-inflammatory effects of rifampicin, ex vivo explants of lesional HS from 8 HS patients were treated with rifampicin, and its effect on cytokine production, immune cells as well as the expression of Toll-like receptor 2 (TLR2) were investigated. Analysis of cell culture medium of rifampicin-treated HS explants revealed an anti-inflammatory effect of rifampicin that significantly inhibiting interleukin (IL)-1β, IL-6, IL-8, IL-10 and tumour necrosis factor (TNF)-α production. Immunohistochemistry of the rifampicin-treated explants suggested a tendency for it to reduce the expression of TLR2 while not affecting the number of immune cells.
Despite all advances in drug delivery, the limitations of the analytical technologies involved in the characterization of next-generation nanomedicines are still impeding further progress of an emerging market. Discriminating between different formulations and batches, drug release is one of the most important quality criteria in development and quality control of pharmaceutics. Unfortunately, there are only few methods available to sensitively measure this important parameter for nanosized carriers. With the development of the dispersion releaser (DR) technology our group has set up a dialysis-based technique that was tested with a number of nanocarrier and nanocrystal formulations such as liposomes and polymeric nanoparticles. By supporting formulation development with a more reliable methodology to assess the drug release from nanosized carriers, a first step has been made to improve future products.