The applicability of pharmaceutical polymeric blends for the fused deposition modelling (FDM) 3D technique: Material considerations-printability-process modulation, with consecutive effects on in vitro release, stability and degradation.

The three dimensional printing (3DP) in the pharmaceutical domain constitutes an alternative, innovative approach compared to the conventional production methods. Fused deposition modelling (FDM), is a simple, cost-effective 3DP technique, however the range of pharmaceutical excipients that can be applied for this methodology is restricted. The study set to define the requirements of the FDM printability, using as technical support custom made, pharmaceutical polymer based filaments and to evaluate if these new dosage forms can live up to the current GMP/GCP quality standards. Formulation rationale was assessed in accordance to the apparatus functionality. Blends were pre-screened based on the processability under the API (carvedilol) thermogravimetric analysis determined critical limit. The technological process implied the use of FDM coupled with hot melt extrusion (HME), while printability was defined by means of thermal, rheological and mechanical measurements. From the pharmaceutical standpoint, the consistency of the in vitro dissolution kinetics was monitored 'at release' and 'in stability', while the print process impact was evaluated based on the previously determined processability potential. Results showed that FDM printability is multifactorial, with brittleness and melt viscosity as primary limitation factors. The increase in shear-thinning and flexural modulus can enable broader processability intervals, which in turn proved to be essential in limiting degradation product formation. The 3DP tablets released the API in an extended rate, however the temperature and humidity along production and storage should be carefully considered as it may affect the final product quality in time. In conclusion, HME + FDM can be considered as an alternative production methodology, with prospects of applicability in the clinical sector, however for some formulations extensive packaging development will be necessary before confirming their suitability.

In vitro and in silico characterization of fibrous scaffolds comprising alternate colistin sulfate-loaded and heat-treated polyvinyl alcohol nanofibrous sheets.

A multilayer mat for dispensing colistin sulfate through a body surface was prepared by electrospinning. The fabricated system comprised various polyvinyl alcohol fibrous layers prepared with or without the active ingredient. One of the electrospun layers contained water-soluble colistin sulfate and the other was prepared from the same polymer type and composition without the active drug and was finally heat-treated. The heat treatment modified the supramolecular structure and conferred the polymer nanofibre with the rate-controlling function. The microstructure of different layers was tracked by positron annihilation lifetime spectroscopy, and detailed morphological analysis of the fibre mats was performed using a scanning electron microscope. The drug-release profiles of various layer arrangements were studied in relation to their antimicrobial activity. The finite element method was applied to overcome the challenge of diffusion-controlled drug release from multilayer polymer scaffolds. The finite element method was first verified using analytical solutions for a simple arrangement (one drug-loaded swellable fibre and one rate-controlling nonswellable fibre) under perfect sink conditions and in a well-stirred finite volume. The effect of alternate layer arrangements on the drug-release profiles was also investigated to plan for controlled topical drug release from fibrous scaffolds. This design is expected to aid in increasing local effectiveness, thus reducing the systemic loading and the consequent side effects of colistin.

Enhanced Injection Molding Simulation of Advanced Injection Molds.

The most time-consuming phase of the injection molding cycle is cooling. Cooling efficiency can be enhanced with the application of conformal cooling systems or high thermal conductivity copper molds. The conformal cooling channels are placed along the geometry of the injection-molded product, and thus they can extract more heat and heat removal is more uniform than in the case of conventional cooling systems. In the case of copper mold inserts, cooling channels are made by drilling and heat removal is facilitated by the high thermal conductivity coefficient of copper, which is several times that of steel. Designing optimal cooling systems is a complex process; a proper design requires injection molding simulations, but the accuracy of calculations depends on how precise the input parameters and boundary conditions are. In this study, three cooling circuit designs and three mold materials (Ampcoloy 940, 1.2311 (P20) steel, and MS1 steel) were used and compared using numerical methods. The effect of different mold designs and materials on cooling efficiency were examined using calculated and measured results. The simulation model was adjusted to the measurement results by considering the joint gap between the mold inserts.