Entwicklung eines Dosiersystems für die individuelle Therapie mit neuen festen oralen Arzneiträgern (English shop)

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The aim of this work was the development of a new dosing system for individualised therapy with solid oral dosage forms. In addition to the dosing system, cylindrical dosage forms were to be developed that can be divided by means of the dosing system into tablet-like, monolithic drug carriers with an individual drug content.

On the basis of a patent application, a dosing system was first developed that is designed for use with a solid cylindrical dosage form. A prototype of the dosing system was constructed. The cylindrical dosage form is placed in a tube-like packaging material in the centre of the dosing system. An adjusting screw and a feed mechanism ensure that the dosage form can be pushed into a defined position by means of a plunger. Furthermore, two different dividing mechanisms were developed that are able to separate defined units from the cylindrical dosage form as drug carriers. The system is referred to as the Solid Dosage Pen.

For practical application, preparations were developed that allow drug carriers to be divided off. Storage stability and in-use stability were investigated. In this work, preparations were developed from three different formulation approaches which could be processed by wet extrusion and melt extrusion into uniformly shaped cylindrical extrudates 5 to 10 cm in length with a diameter of 2.7 to 4.5 mm.

In a wet extrusion process using glycerol 85% as the liquid and two to three polymers, various hydrocolloid matrices were produced. From the extrudates, sustained-release, tablet-like drug carriers containing the active ingredients carvedilol and metoprolol tartrate could be divided off. A force of less than 20 N was required for dividing. The drug carriers individually dosed with the dosing system in the form of tablet-like discs complied with the requirements of the European Pharmacopoeia with regard to uniformity of mass and content. The content remained constant over a storage period of six months under stress conditions.

Using ethanol 96% as well as metoprolol tartrate, sodium hydrogen carbonate, mannitol and tartaric acid, extrudates were obtained in a second wet extrusion process which, after drying, had a diameter of 3 mm. From these, uniformly dosed, individual drug carriers could be divided off. Transferred into water, the drug carriers, as an effervescent preparation, were able to bring the active ingredient metoprolol tartrate into solution in less than two minutes. This dosage form is particularly suitable for use in paediatrics.

By melt extrusion at 40 °C, mannitol, poloxamer 188 and the drug substances carvedilol and metoprolol tartrate were processed into extrudates with a diameter of 3 mm. Drug carriers could be divided off with the dosing system while complying with uniformity of mass and content. The drug carriers released both active ingredients in less than 30 minutes. The stability of the extrudates could also be demonstrated after storage under stress conditions.

In this work, an entirely new system was developed that allows the provision of flexibly dosable, solid, oral, monolithic dosage forms for every need. New characterisation methods for the dosage forms were developed and established methods were transferred to the new system.

The virtually continuous division of dose units makes it possible to supply all patient groups with a single dosing system. Individual dosing by means of solid dosage forms for personalised medicine as well as application in paediatric or geriatric patients can be achieved with this system for the first time. The present work demonstrates preparations and procedures by which drug carriers for the Solid Dosage Pen with immediate disintegration, rapid or sustained drug release can be realised.