Design and production of 3D printed oral capsular devices for the modified release of urea in ruminants.

The use of 3D printing for the production of systems intended for oral delivery of diet supplements in the veterinary pharmacy constitutes an attractive technology that has remained unexplored. In this sense, this work studies the design and 3D printing of capsular devices that allow the modified release of urea, which is frequently used as a source of non-protein nitrogen in ruminants, but highly toxic if fast ingested. The devices were printed with combinations of polylactic acid (PLA, water-insoluble) and polyvinyl alcohol (PVA, water-soluble) in order to modulate the urea release through the different parts. The optimization of the designs as well as printing parameters such as extrusion temperature, printing speed, retraction distance and nozzle speed resulted critical to obtain successful capsular devices. In addition, the dissolution studies confirmed that the developed designs showed a controlled release of urea, especially the ones that presented internal partitions. Finally, Logistic and Weibull equations were the kinetic models that best fitted the experimental data corresponding to functions that describe S-shaped dissolution profiles. Overall, this work constitutes a proof of concept and provides the first steps in the development of 3D printed simple devices for the controlled release of supplements and drugs in veterinary pharmacy.

Binder-free twin-screw melt granulation: An effective approach to manufacture high-dose API formulations.

This study investigates the use of twin-screw binder-free melt granulation (BFMG) in the development of high-dose solid dose formulations for low melting point thermally stable drugs. Both ibuprofen and guaifenesin are examined. By granulating pure API powder, it is shown that BFMG can successfully be used to produce granules that contain 100% API. A design of experiments (DoE) response surface methodology was used to establish the design space for the end-product. The effects of the most relevant process variables (barrel operating temperature, powder feed rate, screw speed and screw configuration) on granule properties (outlet temperature, size distribution, morphology, flowability, compressibility, porosity) and tablet attributes (tensile strength and in-vitro dissolution) were thoroughly studied. Barrel temperature (alone or in interactions with the other variables) represented the most significant variable for both drugs since it governs the formation of granules by partial melting and subsequent agglomeration of the fed powder. Interestingly, the shear action originated by screw speed and screw configuration resulted in various significant responses depending on the drug substance, indicating that it can also be affected by the nature of the processed molecule. Flow properties were improved (i.e., lower Hausner ratio) for both drugs after formation of granules. Tabletability was also tested by preparing 600 mg tablets for all samples. Surprisingly, the resulting granules were highly compactible, requiring only 1% lubricant to form strong tablets containing 96% API and 3% disintegrant. The results also showed that tablets become harder as the granule size increased, especially for guaifenesin. As expected, in-vitro dissolution results indicated that tablets and capsules showed slightly slower dissolution rates than the granules.

3D printing of PVA capsular devices for modified drug delivery: design and in vitro dissolution studies.

The fabrication through FDM 3D printing of hollow systems intended for oral drug delivery constitutes an attractive technology to change personalized medications in the compounding pharmacy. In this sense, this work studied the design and 3D printing of one compartment capsular devices filled of drugs that could require a delayed release mechanism. The optimization of printing parameters such as material flow rate and printing speed by means of simple gcode modifications, resulted critical to allow the production of PVA capsular devices in a single manufacturing process. In addition, the disintegration and dissolution studies of the obtained capsular device confirmed the existence of a delayed drug release compared to commercial hard-gelatin capsules. Furthermore, the use of sinkers in the dissolution tests resulted in similar dissolution profiles regardless the rotation speed. Finally, Gompertz and Weibull equations were the kinetic models that best fitted the experimental data corresponding to immediate release with lag time type profiles. Overall, this work provides insights to understand the effect of the printing parameters on the production of PVA capsular devices and suggests a simple design and single manufacturing process that can be adopted in the future compounding pharmacy.

A process parameters dataset for the extrusion 3D printing of nutraceutical oral dosage forms formulated with monoglycerides oleogels and phytosterols mixtures.

We report the parameter settings used in different 3D printing tests carried out to evaluate the production of nutraceutical oral forms by using mixtures of monoglycerides oleogels and phytosterols as printing materials. The printer employed was an ad-hoc extrusion 3D printing system adapted from a Prusa printer. The dataset here informed would serve as a starting point for the implementation of the 3D printing process to fabricate products using oleogels or printing materials with similar characteristics. This data is related to our recent research article entitled "Extrusion 3D printing of nutraceutical oral dosage forms formulated with monoglycerides oleogels and phytosterols mixtures" [1].

Extrusion 3D printing of nutraceutical oral dosage forms formulated with monoglycerides oleogels and phytosterols mixtures.

Among the potential applications of 3D printing, the development of products with personalized characteristics in the area of food and nutraceuticals represents an important field that must still be explored. The aim of this work was to evaluate the production of nutraceutical oral forms by extrusion-based 3D printing (E3DP) using mixtures of monoglycerides (MG) oleogels and phytosterols (PS) as printing materials. These materials were obtained using MG (10 or 20%wt), high oleic sunflower oil, and variable amounts of PS (20-50%wt PS/oleogel). An ad-hoc extrusion 3D printer composed of a heated syringe and a cooling build platform was used. Rheological tests were carried out to determine the mixtures gel point, in order to select appropriate printing temperatures, as well as the yield stress of the final materials. Hardness of printed forms was obtained by compression tests. Additionally, oral forms were produced by manual extrusion using molds for comparison. It was found that oral forms were successfully printed when using mixtures containing a maximum of 30 and 40%wt PS/oleogel for oleogels formulated with 10 and 20%wt of MG, respectively. Moreover, the best printed forms corresponded to the mixtures with the lowest gelation temperatures. These printed forms were structurally stable, with uniform weight and shape, and maximum hardness of 12.55 N. Hardness values of printed oral forms did not show a correlation with those obtained by manual extrusion using molds, indicating that this parameter was affected by solid composition, cooling rate, and the fragility generated for layers superposition. In conclusion, it was demonstrated that mixtures of MG oleogels and PS can be used for E3DP production of nutraceutical oral forms suggesting that oleogels have excellent potential as materials able to incorporate liposoluble active ingredients to be used as extrusion printing materials.