Two-dimensional printing of nanoparticles as a promising therapeutic method for personalized drug administration.

The necessity for personalized patient treatment has drastically increased since the contribution of genes to the differences in physiological and metabolic state of individuals have been exposed. Different approaches have been considered so far in order to satisfy all of the diversities in patient needs, yet none of them have been fully implemented thus far. In this framework, various types of 2D printing technologies have been identified to offer some potential solutions for personalized medication, which development is increasing rapidly. Accurate drug-on-demand deposition, the possibility of consuming multiple drug substances in one product and adjusting individual drug concentration are just some of the few benefits over existing bulk pharmaceuticals manufacture, which printing technologies brings. With inclusion of nanotechnology by printing nanoparticles from its dispersions some further opportunities such as controlled and stimuli-responsive drug release or targeted and dose depending on drug delivery were highlighted. Yet, there are still some challenges to be solved before such products can reach the pharmaceutical market. In those terms mostly chemical, physical as well as microbiological stability concerns should be answered, with which 2D printing technology could meet the treatment needs of every individual and fulfill some existing drawbacks of large-scale batch production of pharmaceuticals we possess today.

Development of Simvastatin-Loaded Particles Using Spray Drying Method for Ex Tempore Preparation of Cartridges for 2D Printing Technology.

In this work, a spray drying method was developed to produce drug/polymer (simvastatin/polycaprolactone) microparticles that have the potential to be used as a pre-formulation for ex tempore preparation of 2D printing cartridges. An experimental model was designed with the process parameters set to predict the smallest particle size required for successful 2D printing. Three different types of particles (lactose, nanocellulose/lactose, calcium silicate) were produced, and the average size of the dry particles varied depending on the sampling location (cyclone, collection vessel). The encapsulation efficiency of simvastatin was highest with nanocellulose/lactose from the collection vessel. The one-month stability of simvastatin in the particles showed low content, but the addition of ascorbic acid as an antioxidant increased the chemical stability of the drug. Interestingly, the addition of antioxidants decreased the stability of simvastatin in the calcium silicate particles from the collection vessel. Dispersion of the particles in three different propylene glycol and water mixtures (10/90, 50/50, and 90/10% (v/v)), representing a printable ink medium with three different viscosity and surface tension properties, showed that nanocellulose/lactose was the most suitable antiadhesive in terms of dispersed particle size (˂1 µm). After one month of storage, the dispersed particles remained in the same size range without undesirable particle agglomeration.

Nanocellulose-Based Film-Forming Hydrogels for Improved Outcomes in Atopic Skin.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by impaired skin barrier function. Amongst the various dermal formulations that are being used and/or investigated for AD treatment, one of the advanced approaches is the use of hydrogels as film-forming systems that are applied directly to the skin and have the added value of providing a physical barrier, which is lacking in atopic skin. Novel film-forming hydrogels based on two different nanocrystalline celluloses (NCCs) in combination with one of two natural polymers (alginate or pectin) were developed for incorporation of betamethasone dipropionate (BDP). Initially, the low water solubility of BDP was resolved by prior dissolution in a self-microemulsifying drug delivery system (SMEDDS). The mixture of Kolliphor® EL/Capryol® 90 in a ratio of 8/2 was chosen on the merit of its high BDP-saturated solubility and no BDP precipitation upon water dilution, enabling BDP to remain dissolved after incorporation into hydrogels. The solvent evaporation method was used to prepare the films, and their high water retention capacity was confirmed in vitro on artificial membranes and pig ear skin. The presented results thus confirm NCC-based film-forming hydrogels as a very promising drug delivery system for AD treatment.

Particle properties and drug metastable solubility of simvastatin containing PVP matrix particles prepared by electrospraying technique.

In this work the preparation of drug loaded polymeric nanoparticles using electrospraying method and their subsequent characterization is presented. Our purpose was to incorporate the drug with extremely low solubility and low oxidative stability into polyvinylpyrolidone nanoparticles in order to improve its solubility and preserve its chemical stability and hence evaluate the ability of the technology to stabilize such systems in nanoparticulate form. Through the initial screening and optimization of process parameters and polymer solution properties, we detected different morphologies of electrosprayed product particles, where the use of lower molecular weight polymer resulted in a higher process instability as well as in a broader particle size distribution. On the other hand, the solution containing polyvinylpyrolidone with higher molecular weight showed sensitivity to different flow rates and electric field changes, which again resulted in differing the particle size and morphology. The electrosprayed products, prepared by sufficient process stability and having adequately narrow size distribution span, showed lower initial simvastatin contents than theoretically expected, which indicated an oxidative drug degradation already during the electrospraying process. The addition of antioxidants improved simvastatin chemical stability in the particles, during the process itself as well as after accelerated stability study. With an addition of butylated hydroxyanisole antioxidant mixture into initial polymer solution more than 95% of the drug content was preserved after one month at accelerated conditions, whereas in formulations without antioxidants simvastatin content was less than 6%. Antioxidants addition however did not influence only simvastatin stability but also simvastatin solubility. Surprisingly, antioxidants addition did decrease drug solubility in buffers (pH=4 and pH=6.8) for more than a half without any solid state changes of simvastatin. Potential hydrophobic interaction between simvastatin and antioxidants are hindering the drug solubility in the respective buffer, despite drug being in amorphous state.