Growing demand for customized pharmaceutics and medical devices makes the impact of additive manufacturing increased rapidly in recent years. The 3D printing has become one of the most revolutionary and powerful tool serving as a technology of precise manufacturing of individually developed dosage forms, tissue engineering and disease modeling. The current achievements include multifunctional drug delivery systems with accelerated release characteristic, adjustable and personalized dosage forms, implants and phantoms corresponding to specific patient anatomy as well as cell-based materials for regenerative medicine. This review summarizes the newest achievements and challenges of additive manufacturing in the field of pharmaceutical and biomedical research that have been published since 2015. Currently developed techniques of 3D printing are briefly described while comprehensive analysis of extrusion-based methods as the most intensively investigated is provided. The issue of printlets attributes, i.e. shape and size is described with regard to personalized dosage forms and medical devices manufacturing. The undeniable benefits of 3D printing are highlighted, however a critical view resulting from the limitations and challenges of the additive manufacturing is also included. The regulatory issue is pointed as well.
In this paper, we investigated the molecular mobility and physical stability of amorphous bicalutamide, a poorly water-soluble drug widely used in prostate cancer treatment. Our broadband dielectric spectroscopy measurements and differential scanning calorimetry studies revealed that amorphous BIC is a moderately fragile material with a strong tendency to recrystallize from the amorphous state. However, mixing the drug with polymer polyvinylpyrrolidone results in a substantial improvement of physical stability attributed to the antiplasticizing effect governed by the polymer additive. Furthermore, IR study demonstrated the existence of specific interactions between the drug and excipient. We found out that preparation of bicalutamide-polyvinylpyrrolidone mixture in a 2-1 weight ratio completely hinder material recrystallization. Moreover, we determined the time-scale of structural relaxation in the glassy state for investigated materials. Because molecular mobility is considered an important factor governing crystallization behavior, such information was used to approximate the long-term physical stability of an amorphous drug and drug-polymer systems upon their storage at room temperature. Moreover, we found that such systems have distinctly higher water solubility and dissolution rate in comparison to the pure amorphous form, indicating the genuine formulation potential of the proposed approach.
The design of nanodelivery systems has been recently considered as a solution to the major challenge in pharmaceutical research - poor bioavailability of lipophilic drugs. Nanocapsules with liquid oil cores and shells based on amphiphilic polysaccharides were developed here as robust carriers of hydrophobic active compounds. A series of modified charged hyaluronates were synthesized and used as stabilizing shells ensuring also the biocompatibility of the nanocapsules that is crucial for applications related to the delivery of lipophilic drugs in vivo. Importantly, the oil nanodroplets were found to be stably suspended in water for at least 15 months without addition of low molar mass surfactants. Moreover, their size and stability may be tuned by varying the relative content of hydrophobic and hydrophilic groups in the hyaluronate derivatives as was confirmed by dynamic light scattering and nanoparticle tracking analysis as well as electron microscopy. In vivo studies demonstrated that hyaluronate-based nanocapsules accumulated preferentially in the liver as well as in the lungs. Moreover, their accumulation was dramatically potentiated in endotoxemic mice. In vitro studies showed that the nanocapsules were taken up by liver sinusoidal endothelial cells and by mouse lung vascular endothelial cells. Importantly, the capsules were found to be nontoxic in an acute oral toxicity experiment even at a dose of 2000 mg per kg b.w. Biocompatible hyaluronate-based nanocapsules with liquid cores described herein represent a promising and tunable nanodelivery system for lipophilic active compounds via both oral and intravenous administration.
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