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.
Hydrogel wound dressings are highly effective in the therapy of wounds. Yet, most of them do not contain any active ingredient that could accelerate healing. The aim of this study was to prepare hydrophilic active dressings loaded with an anti-inflammatory compound - trans-resveratrol (RSV) of hydrophobic properties. A special attention was paid to select such a technological strategy that could both reduce the risk of irritation at the application site and ensure the homogeneity of the final hydrogel. RSV dissolved in Labrasol was combined with an aqueous sol of poly(vinyl) alcohol (PVA), containing propylene glycol (PG) as a plasticizer. This sol was transformed into a gel under six consecutive cycles of freezing (-80 °C) and thawing (RT). White, uniform and elastic membranes were successfully produced. Their critical features, namely microstructure, mechanical properties, water uptake and RSV release were studied using SEM, DSC, MRI, texture analyser and Franz-diffusion cells. The cryogels made of 8 % of PVA showed optimal tensile strength (0.22 MPa) and elasticity (0.082 MPa). The application of MRI enabled to elucidate mass transport related phenomena in this complex system at the molecular (detection of PG, confinement effects related to pore size) as well as at the macro level (swelling). The controlled release of RSV from membranes was observed for 48 h with mean dissolution time of 18 h and dissolution efficiency of 35 %. All in all, these cryogels could be considered as a promising new active wound dressings.
The self-assembly phenomenon of amphiphiles has attracted particular attention in recent years due to its wide range of applications. The formation of nanoassemblies able to solubilize sparingly water-soluble drugs was found to be a strategy to solve the problem of poor solubility of active pharmaceutical ingredients. Binary and ternary solid dispersions containing Biopharmaceutics Classification System (BCS) class II drug bicalutamide and either Poloxamer®188 or Poloxamer®407 as the surface active agents were obtained by either spray drying or solvent evaporation under reduced pressure. Both processes led to morphological changes and a reduction of particle size, as confirmed by scanning electron microscopy and laser diffraction measurements. The increase in powder wettability was confirmed by means of contact angle measurements. The effect of an alteration of the crystal structure was followed by powder X-ray diffractometry while thermal properties were determined using differential scanning calorimetry. Interestingly, bicalutamide exhibited a polymorph transition after spray drying with the poloxamer and polyvinylpyrrolidone (PVP), while the poloxamer underwent partial amorphization. Moreover, due to the surface activity of the carrier, the solid dispersions formed nanoaggregates in water, as confirmed using dynamic light scattering measurements. The aggregates measuring 200–300 nm in diameter were able to solubilize bicalutamide inside the hydrophobic inner parts. The self-assembly of binary systems was found to improve the amount of dissolved bicalutamide by 4- to 8-fold in comparison to untreated drug. The improvement in drug dissolution was correlated with the solubilization of poorly soluble molecules by macromolecules, as assessed using emission spectroscopy.
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