Material compatibility and processing challenges in droplet deposition modelling additive manufacturing: A study on pharmaceutical excipients Polyvinylpyrrolidone/vinyl acetate (PVP/VA) and Polycaprolactone (PCL).

Additive manufacturing (AM) enables the production of complex, lightweight, and customized components with superior quality. Selecting the right materials considering their thermal properties, printability, and layer adhesion is crucial in melting-based AM techniques. This study investigates Droplet Deposition Modelling (DDM), an innovative material extrusion process that utilizes thermoplastic granules. DDM is distinguished by its shorter manufacturing times and a wider range of materials, setting it apart from traditional material extrusion methods such as fused filament fabrication. We investigated the printability and part quality in DDM using two common pharmaceutical excipients: Polyvinylpyrrolidone/vinyl acetate 6:4 (PVP/VA), which is highly brittle, and Polycaprolactone (PCL), known for its low solubility and role in controlled drug release. Different ratios of PVP/VA and PCL were compounded via hot melt extrusion (HME) and used in DDM to study the impact of ingredient content on printability and part quality, employing geometrical models to assess material compatibility and printability. The study revealed that increasing PVP/VA content leads to higher viscosity, reduced flowability, and uneven deposition, with formulations of 80 % and 100 % PVP/VA showing poor processability. In contrast, formulations with 60 % and 40 % PVP/VA exhibited smooth processing and compatibility with DDM. We identified processing temperature and Drop Aspect Ratio (DAR) as key factors influencing material printability and part quality. Elevated processing temperatures and reduced DAR were found to increase interface temperatures, reduce diffusion, and potentially cause the 'elephant feet' issue. Additionally, smaller droplet sizes and material characteristics, such as higher interfacial tension in PCL, could lead to coalescence. Our findings highlight the complexities in optimizing DDM processing parameters and material blends, underscoring the need for careful formulation design to achieve high-quality 3D printed products.

Tailoring drug release in bilayer tablets through droplet deposition modeling and injection molding.

This study explores the innovative production of personalized bilayer tablets, integrating two advanced manufacturing techniques: Droplet Deposition Modeling (DDM) and Injection Molding (IM). Unlike traditional methods limited to customizing dense bilayer medicines, our approach uses Additive Manufacturing (AM) to effectively adjust drug release profiles. Focusing on Caffeine and Paracetamol, we found successful processing for both DDM and IM using Caffeine formulation. The high viscosity of Paracetamol formulation posed challenges during DDM processing. Integrating Paracetamol formulation for the over-molding process proved effective, demonstrating IM's versatility in handling complex formulations. Varying infill percentages in DDM tablets led to distinct porosities affecting diverse drug release profiles in DDM-fabricated tablets. In contrast, tablets with high-density structures formed through the over-molding process displayed slower and more uniform release patterns. Combining DDM and IM techniques allows for overcoming the inherent limitations of each technique independently, enabling the production of bilayer tablets with customizable drug release profiles. The study's results offer promising insights into the future of personalized medicine, suggesting new pathways for the development of customized oral dosage forms.

A comparison of droplet deposition modelling, fused filament fabrication, and injection moulding for the production of oral dosage forms containing hydrochlorothiazide.

Additive manufacturing (AM) possesses a transformative potential to revolutionize personalized medicine fabrication. Fused filament fabrication (FFF), an advanced AM technique, enables the development of tailored medicines with customizable dosages and controlled release properties. Nevertheless, filament prerequisites impose material limitations and present considerable challenges, necessitating a comprehensive evaluation of mechanical, rheological, and thermal characteristics to circumvent complications during the FFF process. Droplet deposition modeling (DDM), an innovative AM approach derived from injection molding (IM) technology, processes granulate feedstock to facilitate the production of personalized medicines. This study delves into the effects of FFF, DDM, and IM techniques on the release profiles of Hydrochlorothiazide, a widely employed drug for hypertension and edema treatment. By varying infill density, the investigation assesses the manufactured tablets using DDM and FFF methods. Our findings show that tablets made with FFF and DDM with identical infill densities had distinct microstructures, resulting in variable drug release profiles. Decreasing the infill densities resulted in higher sample porosity, leading to an accelerated drug release rate. A comparative analysis of drug release profiles from DDM and IM fabricated tablets demonstrated notable differences, despite DDM's origins in injection molding technology. This comprehensive study underscores the significance of not only infill densities but also the choice of manufacturing technique, as both factors can profoundly influence drug release profiles. By shedding light on these considerations, the research contributes to the ongoing advancement of personalized medicine through additive manufacturing technologies.

Hybrid Manufacturing of Oral Solid Dosage Forms via Overprinting of Injection-Molded Tablet Substrates.

Since 3D printing allows for patient-specific dosage forms, it has become a major focus in pharmaceutical research. However, it is difficult to scale up drug product manufacturing. Injection molding has been used in conjunction with hot-melt extrusion to mass produce drug products, but making tailored solid dosage forms with this technology is neither cost-effective nor simple. This study explored the use of a combination of fused filament fabrication and injection molding to create patient-specific solid dosage forms. A tablet fixation and location template was used to overprint directly on injection-molded tablet bases, and theophylline was combined with polycaprolactone and Kollidon® VA64 via hot-melt extrusion to produce the filament. Dynamic mechanical analysis was used to evaluate the brittleness of the filament, and differential scanning calorimetry was used to analyze the thermal results. The results showed that theophylline had a flow promoting effect on the polymer blend and that overprinted tablets were manufactured faster than 3D-printed tablets. Drug release studies also showed that overprinted tablets released faster than injection-molded tablets. This method demonstrates the potential of hybrid manufacturing for the pharmaceutical industry as a means of bridging the gap between personalized dosage forms and mass production.

Effect of cimetidine on catalase activity of Pseudomonas aeruginosa: a suggested mechanism of action.

Catalase is an important enzyme for the degradation of hydrogen peroxide in cells. Bacteria have potent catalase to deal with H2O2 in their medium culture. Any chemicals that inhibit catalase activity can be harmful for cells. Histamine H2 antagonist drugs such as cimetidine and ranitidine are used for the treatment of gastrointestinal tract disorders. The present results showed that cimetidine could inhibit the catalase activity of Pseudomonas aeruginosa in a competitive inhibition. The determination of IC50 value and Ki (6.5 µM) of cimetidine demonstrated that the enzyme binds to the drug with high affinity. Binding of the drug to the enzyme was pH-dependent and no binding was observed at basic pH (>9) and acidic pH (<6). Moreover, the imidazole ring and cyanoguanidine group of cimetidine may play an important role in inhibition by binding to Fe in heme group and glutamic acid 51 residue on the enzyme, respectively. Ranitidine had no effect on the catalase activity.