Hans-Michael Wolff

Optimal process design for the manufacture of transdermal drug delivery systems

In a pharmaceutical market characterized by increasing competition, assessment criteria related to system design are assuming greater importance. This is true for both conventional dosage forms and drug delivery systems (DDS), as manufacturers strive to achieve adequate patient convenience and compliance. At the same time, the process design for the manufacture of DDS must comply with current good manufacturing practices, and give sufficient consideration to associated environmental issues. Related problems must be solved under social and safety pressures, which, in turn, become economic pressures, such as the consideration of control methods. In addition, both the system design and the process design have a major impact on the cost of goods, as well as on the levels of complexity or risk associated with development.

In vitro and in vivo release of estradiol from an intra-muscular microsphere formulation

In vitro 17β-estradiol release from controlled-release microspheres intended for intra-muscular administration was investigated using a rotating bottle apparatus. Prior to intra-muscular administration of 17β-estradiol loaded microspheres the in vivo pharmacokinetics of 17β-estradiol in NZW rabbits were determined: the clearance value was 50.0 ± 8.1 l/d/kg and the elimination half-life was 7.7 ± 2.2 min (n = 6 ± S.D.). The release of 17β-estradiol from the microspheres in vivo was determined and compared to the release profile obtained in vitro using two release protocols. There was a linear relationship from day 0 until day 30 irrespective of which in vitro test protocol was used. It is suggested that the rotating bottle apparatus is a good starting point for the development of an in vitro release test method for controlled-released intra-muscular dosage forms. Possible strategies for the improvement of an in vitro test to predict in vivo release are discussed.

Galenische Entwicklung von transdermalen Systemen

An Beispielen von wirkstoffbeladenen Adhasivfihnen werden Konzepte, Herstellmethoden und galenische Optimierungsmoglichkeiten in der TTS-Entwicklung skizziert. Abgesehen von biologischen Faktoren sind fur die in-vivo-Freisetzung Steuerungselemente, Reservoireigenschaften und Adhasion der Arzneiform von wesentlicher Bedeutung. Mit Matrixpflastern kann in wichtigen Anwendungsbeispielen (z. B. Nikotin-, Nitroglycerin-Pflaster) eine hohe Ausschopfung des Wirkstoffreservoirs und eine nichtlineare in-vivo-Freisetzungscharakteristik innerhalb kurzer Applikationspe-rioden realisiert werden. Essentiell fur die Funktionsfahigkeit selbstklebender Matrizes sind eine hohe thermodynamische Aktivitat des Arzneistoffes und optimale viskoelasti-sche Eigenschaften.