Influence of the formulation on the tolerance profile of nanoparticle-bound doxorubicin in healthy rats: focus on cardio- and testicular toxicity.

A toxicological study of doxorubicin bound to poly(butyl cyanoacrylate) or human serum albumin nanoparticles coated with polysorbate 80 was performed in healthy rats. The doxorubicin formulations were injected at a therapeutic dose regimen (3 x 1.5 mg/kg with a 72 h interval), and the animals were followed up for 15 or 30 days. The overall result of this study suggests that the surfactant-coated nanoparticle formulations of doxorubicin have favorable toxicological profiles. Specifically, these formulations display a considerably reduced cardio- and testicular toxicity, as compared to a free drug.

Transdermal therapeutic systems--actual state and future developments.

Modern transdermal therapeutic systems have been marketed since the last decade only. Nitroglycerin, scopolamine, clonidine, estradiol and nicotine are the current prominent representatives that have matched expectations regarding therapeutical benefits based on TTS applications. Although different TTS constructions have been realized, it is nevertheless appropriate to consider the governing role of the skin permanent. As the upper skin barrier limits flux rates, drug uptake has to be improved by the TTS's own occlusion or by flux enhancers. Enhancers act either on the hydrophilic keratin matrix or on the lipophilic intercellular material in the stratum corneum. Improvements in drug diffusion must be balanced carefully with the risk of skin irritation. In the future we should expect, among others, pulsatile systems to avoid tolerance, or systems comprising fixed combinations of transdermal drugs within one TTS, possibly at first in the field of hormones. Other expectations will be discussed. Therapeutic benefits are expected by the administration of highly potent topical drugs by means of TTS-analogous therapeutic systems, enabling a time-controlled drug release for purposes of topical treatment only.

[Drug release in vitro from digoxin formulations with high bioavailability (author's transl)]. / Wirkstoffliberation in vitro bei Digoxin-Präparaten mit hoher Bioverfügbarkeit.

The drug release of four brands of digoxin tablets (A, B, C, D) with known bioavailability was examined using three liberation systems. The paddle method (1) could only ascertain a uniformly good release of all brands. A flow-cell (II) and a special method testing the supersaturation (III) indicated significant differences in drug release. Both II and III pointed to the brand having the best bioavailability. Beyond it no satisfactory correlation was found between the values of bioavailability and drug release.

[Enhanced bioavailability of digoxin from silica matrix formulations (author's transl)]. / Erhöhte Bioverfügbarkeit von Digoxin aus Kieselsäure-Matrix-Zubereitungen.

The bioavailability of digoxin from 3 silica matrix formulations was assessed in single-dose crossover studies in 12 healthy human volunteers: digoxin/silica matrix tablets (I, Digacin), digoxin/silica matrix in capsule form (II) and digoxin/silica matrix dragées, protected against gastrict juice by film coating (III). Urinary glycoside excretion for 6 days after 0.5 mg doses were measured by radioimmunoasay. Referring to an intravenous injection the bioavailability of digoxin from Digacin tablets is 82%, from the encapsulated matrix 69%, and from the dragées 54%. In comparison with corresponding results from other investigators Digacin tablets havet the same high bioavailability as digoxin solutions. In vitro liberations of digoxin from the silica matrix formulations (94% in 90 s) is significantly better than from conventional tablets produces from a digoxin-lactose trituration (61% in 90 s).