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Fiber-based technologies are widely used in various industries, but their use in pharmaceuticals remains limited. While melt extrusion is a standard method for producing medical fibers such as sutures, it is rarely used for pharmaceutical fiber-based dosage forms. The EsoCap system is a notable exception, using a melt-extruded water-soluble filament as the drug release trigger mechanism. The challenge of producing drug-loaded fibers, particularly due to the use of spinning oils, and the processing of the fibers are addressed in this work using other approaches. The aim of this study was to develop processes for the production and processing of pharmaceutical fibers for targeted drug delivery. Fibers loaded with polyvinyl alcohol and fluorescein sodium as a model drug were successfully prepared by a continuous melt extrusion process and directly spun. These fibers exhibited uniform surface smoothness and consistent tensile strength. In addition, the fibers were further processed into tubular dosage forms using a modified knitting machine and demonstrated rapid drug release in a flow cell.

The increasing prevalence of esophageal disease highlights the clinical relevance of novel, long-lasting mucoadhesive oral dosage forms. The EsoCap device enables targeted local application of films in the esophagus. Biorelevant test systems such as EsoPeriDiss are essential for early formulation development. To this end, the developed and already described release model for simulating the esophagus is being further developed for its potential for biorelevant mapping of the application site through complete tempering and investigation of biorelevant release media. Particularly viscous saliva formulations led to an extension of the retention time. In addition, possible formulation strategies for increasing the retention time of esophageal applied films are being evaluated, such as different film thicknesses, polymer grades and the influence of different active ingredient properties on the retention time. For highly soluble active ingredients, the film thickness represents an option for extending the retention time, while for less soluble substances, the choice of polymer grade may be of particular interest.

The absorption of drugs with narrow absorption windows in the upper small intestine can be improved with a mucoadhesive drug delivery system such as enteric films. To predict the mucoadhesive behaviour in vivo, suitable in vitro or ex vivo methods can be performed. In this study, the influence of tissue storage and sampling site on the mucoadhesion of polyvinyl alcohol film to human small intestinal mucosa was investigated. Tissue from twelve human subjects was used to determine adhesion using a tensile strength method. Thawing of tissue frozen at -20 °C resulted in a significantly higher work of adhesion ( p = 0.0005) when a low contact force was applied for one minute, whereas the maximum detachment force was not affected. When the contact force and time were increased, no differences were found for thawed tissue compared to fresh tissue. No change in adhesion was observed depending on the sampling location. Initial results from a comparison of adhesion to porcine and human mucosa suggest that the tissues are equivalent.

Sparkling water is said to increase gastric motility by the release of carbon dioxide, thereby potentially affecting the pharmacokinetics of orally administered drugs. The hypothesis of the present work was that the induction of gastric motility by intragastric release of carbon dioxide from effervescent granules could promote the mixing of drugs into the chyme under postprandial conditions, resulting in a prolonged drug absorption. For this purpose, an effervescent and a non-effervescent granule formulation of caffeine as a marker for gastric emptying were developed. In a three-way crossover study with twelve healthy volunteers, the salivary caffeine pharmacokinetics, after administration of the effervescent granules with still water and the administration of the non-effervescent granules with still and sparkling water, were investigated after intake of a standard meal. While the administration of the effervescent granules with 240 mL of still water led to a significantly prolonged gastric residence of the substance compared to the administration of the non-effervescent granules with 240 mL still water, the application of the non-effervescent granules with 240 mL sparkling water did not prolong gastric residence via mixing into caloric chyme. Overall, the mixing of caffeine into the chyme following the administration of the effervescent granules did not seem to be a motility mediated process.

Fibers and yarns are part of everyday life. So far, fibers that are also used pharmaceutically have mainly been produced by electrospinning. The common use of spinning oils and the excipients they contain, in connection with production by melt extrusion, poses a regulatory challenge for pharmaceutically usable fibers. In this publication, a newly developed small-scale direct-spinning melt extrusion system is described, and the pharmaceutically useful polyvinyl filaments produced with it are characterized. The major parts of the system were newly developed or extensively modified and manufactured cost-effectively within a short time using rapid prototyping (3D printing) from various materials. For example, a stainless-steel spinneret was developed in a splice design for a table-top melt extrusion system that can be used in the pharmaceutical industry. The direct processing of the extruded fibers was made possible by a spinning system developed called Spinning-Rosi, which operates continuously and directly in the extrusion process and eliminates the need for spinning oils. In order to prevent instabilities in the product, further modifications were also made to the process, such as a the moisture encapsulation of the melt extrusion line at certain points, which resulted in a bubble-free extrudate with high tensile strength, even in a melt extrusion line without built-in venting.

There are no methods for specific local application of active substances to the mucosa of the esophagus to treat eosinophilic esophagitis or other esophageal diseases. This publication describes the principal in vivo functionality and acceptance of a novel modular drug delivery concept, called EsoCap system, by 12 healthy volunteers. For the first time, the EsoCap system enables targeted placement on the esophageal mucosa of a mucoadhesive polymer film. Acceptance was determined by means of a standardized questionnaire after administration and functionality of the device by MRI scans. Two different setups of the EsoCap system were tested: one setup with a density of 0.4 g/cm 3 and one with a density of 1.0 g/cm 3 . Acceptability of the dosage form was also confirmed in addition to functionality, by measuring the applied film length. It was found that acceptance of the variant with the higher density was significantly better. This novel drug delivery technology could enable a targeted, local and long-lasting therapy of the esophagus for the first time, depending on the polymer film used.