Polyvinyl Alcohol-Based 3D Printed Tablets: Novel Insight into the Influence of Polymer Particle Size on Filament Preparation and Drug Release Performance.

Three-dimensional printing (3DP) by fused deposition modeling (FDM) has gained momentum as a promising pharmaceutical manufacturing method due to encouraging forward-looking perspectives in personalized medicine preparation. The current challenges the technology has for applicability in the fabrication of solid dosage forms include the limited range of suitable pharmaceutical grade thermoplastic materials. Hence, it is important to investigate the implications of variable properties of the polymeric carrier on the preparation steps and the final output, as versatile products could be obtained by using the same material. In this study, we highlighted the influence of polyvinyl alcohol (PVA) particle size on the residence time of the mixtures in the extruder during the drug-loaded filament preparation step and the consequent impact on drug release from the 3D printed dosage form. We enhanced filament printability by exploiting the plasticizing potential of the active pharmaceutical ingredient (API) and we explored a channeled tablet model as a design strategy for dissolution facilitating purposes. Our findings disclosed a new perspective regarding material considerations for the preparation of PVA-based solid dosage forms by coupling hot melt extrusion (HME) and FDM-3DP.

Electrospun amorphous solid dispersions of meloxicam: Influence of polymer type and downstream processing to orodispersible dosage forms.

The objectives of this work were to develop meloxicam based amorphous solid dispersion through electrospinning technique and evaluate the effect of the polymeric matrix on the physicochemical properties of the fibers and the downstream processing ability to orodispersible dosage forms. Drug - polymer interactions formed between Eudragit E and meloxicam, confirmed through Raman and 1HNMR spectra, enabled the development of fibers from ethanol, thus allowing an increased production rate compared to PVPk30 where a DMF:THF solvent system was suitable. Microflux dissolution-permeation studies showed a significantly higher diffusion from amorphous solid dispersions compared to crystalline meloxicam. The flux through the membrane was influenced by the polymers only under basic conditions, where the precipitation of Eudragit E limited the complete resolubilization of the active ingredient. This phenomenon was not observed during large volume conventional dissolution testing. The effect of formulation on long term stability could not be highlighted as all products were stable up to 15 months, stored in closed holders at 25 °C ±â€¯2 °C and 50%RH ±â€¯10%. The increased surface area of fibers enabled tablet preparation with low pressures due to favorable bonding between particles during compression. PVPk30 formulation presented higher tabletability and compactability, as higher tensile strength compacts could be prepared. Eudragit E formulation had lower detachment and ejection stress, suggesting a lower sticking tendency during tableting. The presence of HPßCD in PVPk30 formulation offered improved morphological features of the fibers, however no significant effect was observed on dissolution, permeation or mechanical properties. Downstream processing was guided by polymer mechanical properties and solubility, thus PVPk30 fibers could be delivered in the form of orodispersible webs and conventional tablets, whereas Eudragit E fibers as orodispersible tablets.

Data fusion strategies for performance improvement of a Process Analytical Technology platform consisting of four instruments: An electrospinning case study.

The aim of this work was to develop a PAT platform consisting of four complementary instruments for the characterization of electrospun amorphous solid dispersions with meloxicam. The investigated methods, namely NIR spectroscopy, Raman spectroscopy, Colorimetry and Image analysis were tested and compared considering the ability to quantify the active pharmaceutical ingredient and to detect production errors reflected in inhomogeneous deposition of fibers. Based on individual performance the calculated RMSEP values ranged between 0.654% and 2.292%. Mid-level data fusion consisting of data compression through latent variables and application of ANN for regression purposes proved efficient, yielding an RMSEP value of 0.153%. Under these conditions the model could be validated accordingly on the full calibration range. The complementarity of the PAT tools, demonstrated from the perspective of captured variability and outlier detection ability, contributed to model performance enhancement through data fusion. To the best of the author's knowledge, this is the first application of data fusion in the field of PAT for efficient handling of big-analytical-data provided by high-throughput instruments.

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.