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It was the aim of this study to develop high drug loaded (>30%, w/w), thermoplastic polyurethane (TPU)-based dosage forms via fused deposition modelling (FDM). Model drugs with different particle size and aqueous solubility were pre-processed in combination with diverse TPU grades via hot melt extrusion (HME) into filaments with a diameter of 1.75 ± 0.05 mm. Subsequently, TPU-based filaments which featured acceptable quality attributes (i.e. consistent filament diameter, smooth surface morphology and good mechanical properties) were printed into tablets. The sustained release potential of the 3D printed dosage forms was tested in vitro. Moreover, the impact of printing parameters on the in vitro drug release was investigated. TPU-based filaments could be loaded with 60% (w/w) fine drug powder without observing severe shark skinning or inconsistent filament diameter. During 3D printing experiments, HME filaments based on hard TPU grades were successfully converted into personalized dosage forms containing a high concentration of crystalline drug (up to 60%, w/w). In vitro release kinetics were mainly affected by the matrix composition and tablet infill degree. Therefore, this study clearly demonstrated that TPU-based FDM feedstock material offers a lot of formulation freedom for the development of personalized dosage forms., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The aim of the present study was to develop thermoplastic polyurethane (TPU)-based intravaginal rings (IVRs) for prophylaxis and treatment of bacterial vaginosis via hot melt extrusion/injection molding. Therefore, different TPU grades were processed in combination with lactic acid or metronidazole, targeting a sustained lactic acid release over a 28day-period and sustained metronidazole release over 4-7days. Hot melt extrusion of lactic acid/TPU combinations required a lower extrusion temperature due to the plasticizing properties of lactic acid, evidenced by the lower glass transition temperature (T g ) and cross-over point (T tanδ = 1 ) values. NIR-chemical imaging data showed a homogenous distribution of lactic acid in TPU matrices at drug loads up to 30% (w/w). The addition of metronidazole did not lower processing temperatures, as the active pharmaceutical ingredient remained crystalline in the TPU matrix. Hydrophobic TPUs with a low ratio between the soft and hard segments (SS/HS ratio) in the polymer structure were suitable carriers for the lactic acid-eluting device over a 28-day period, while hydrophilic TPUs were needed to achieve the required release rate of metronidazole-eluting IVRs. IVRs manufactured with a TPU grade having a higher SS/HS ratio and lactic acid/TPU ratio exhibited a more elastic behavior. The addition of 25% (w/w) metronidazole did not affect the mechanical properties of the IVRs. Hydrophilic TPUs were most prone to biofilm formation by Candida albicans and Staphylococcus aureus, but the incorporation of metronidazole in the device prevented biofilm formation. Based on the drug eluting performance and mechanical tests, a mixture of lactic acid and Tecoflex™ EG-93A (20/80, w/w) and a combination of metronidazole and Tecophilic™ SP-93A-100 (25/75, w/w) were selected to design IVRs for the prophylaxis and treatment of bacterial vaginosis, respectively. Slug mucosal irritation tests predicted low irritation potency for both devices., (Copyright © 2017 Elsevier B.V. All rights reserved.)

During this project 3 techniques (twin screw melt granulation/compression (TSMG), hot melt extrusion (HME) and injection molding (IM)) were evaluated for the manufacturing of thermoplastic polyurethane (TPU)-based oral sustained release matrices, containing a high dose of the highly soluble metformin hydrochloride. Whereas formulations with a drug load between 0 and 70% (w/w) could be processed via HME/(IM), the drug content of granules prepared via melt granulation could only be varied between 85 and 90% (w/w) as these formulations contained the proper concentration of binder (i.e. TPU) to obtain a good size distribution of the granules. While release from HME matrices and IM tablets could be sustained over 24h, release from the TPU-based TSMG tablets was too fast (complete release within about 6h) linked to their higher drug load and porosity. By mixing hydrophilic and hydrophobic TPUs the in vitro release kinetics of both formulations could be adjusted: a higher content of hydrophobic TPU was correlated with a slower release rate. Although mini-matrices showed faster release kinetics than IM tablets, this observation was successfully countered by changing the hydrophobic/hydrophilic TPU ratio. In vivo experiments via oral administration to dogs confirmed the versatile potential of the TPU platform as intermediate-strong and low-intermediate sustained characteristics were obtained for the IM tablets and HME mini-matrices, respectively., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Hydrophilic aliphatic thermoplastic polyurethane (Tecophilic™ grades) matrices for high drug loaded oral sustained release dosage forms were formulated via hot melt extrusion/injection molding (HME/IM). Drugs with different aqueous solubility (diprophylline, theophylline and acetaminophen) were processed and their influence on the release kinetics was investigated. Moreover, the effect of Tecophilic™ grade, HME/IM process temperature, extrusion speed, drug load, injection pressure and post-injection pressure on in vitro release kinetics was evaluated for all model drugs. (1)H NMR spectroscopy indicated that all grades have different soft segment/hard segment ratios, allowing different water uptake capacities and thus different release kinetics. Processing temperature of the different Tecophilic™ grades was successfully predicted by using SEC and rheology. Tecophilic™ grades SP60D60, SP93A100 and TG2000 had a lower processing temperature than other grades and were further evaluated for the production of IM tablets. During HME/IM drug loads up to 70% (w/w) were achieved. In addition, Raman mapping and (M)DSC results confirmed the homogenous distribution of mainly crystalline API in all polymer matrices. Besides, hydrophilic TPU based formulations allowed complete and sustained release kinetics without using release modifiers. As release kinetics were mainly affected by drug load and the length of the PEO soft segment, this polymer platform offers a versatile formulation strategy to adjust the release rate of drugs with different aqueous solubility., (Copyright © 2016 Elsevier B.V. All rights reserved.)