The aim of this study was to prepare benzydamine hydrochloride loaded orodispersible films using modified semisolid extrusion 3D printing method. An innovative approach was developed where thin layer of drug loaded dispersion is printed and dried before printing of subsequent layers. Layer-by-layer drying as the in process step improves mechanical properties of films, uniformity of drug content and allows faster preparation of films in compounding settings due to shortening of drying time. Orodispersible films consisted of film forming maltodextrin, sorbitol as a plasticizer and hydroxyethylcellulose as a thickening agent. The height of the digital model showed excellent correlation with the disintegration time, weight, thickness and mechanical properties of prepared films. Drug content, predefined by volume of digital model and concentration of drug in print dispersion, showed excellent uniformity. The modified printing method shows great promise in a compounding production of personalized film dosage forms, and brings in possibilities such as one step preparation of films with compartmented drugs and incorporation of taste masking or release control layers.

• Klíčová slova
• 3D printing, Benzydamine hydrochloride, Multilayer, Orodispersible films, Personalization,
• MeSH
• 3D tisk * MeSH
• benzydamin chemie   MeSH
• celulosa analogy a deriváty   chemie   MeSH
• farmaceutická technologie metody   MeSH
• lékové transportní systémy * MeSH
• pomocné látky chemie   MeSH
• viskozita MeSH
• vysoušení MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzydamin MeSH
• celulosa MeSH
• hydroxyethylcellulose MeSH Prohlížeč
• pomocné látky MeSH

Three-dimensional printing (3DP) has gained popularity among scientists and researchers in every field due to its potential to drastically reduce energy costs for the production of customized products by utilizing less energy-intensive machines as well as minimizing material waste. The 3D printing technology is an additive manufacturing approach that uses material layer-by-layer fabrication to produce the digitally specified 3D model. The use of 3D printing technology in the pharmaceutical sector has the potential to revolutionize research and development by providing a quick and easy means to manufacture personalized one-off batches, each with unique dosages, distinct substances, shapes, and sizes, as well as variable release rates. This overview addresses the concept of 3D printing, its evolution, and its operation, as well as the most popular types of 3D printing processes utilized in the health care industry. It also discusses the application of these cutting-edge technologies to the pharmaceutical industry, advancements in various medical fields and medical equipment, 3D bioprinting, the most recent initiatives to combat COVID-19, regulatory frameworks, and the major challenges that this technology currently faces. In addition, we attempt to provide some futuristic approaches to 3DP applications.

• Klíčová slova
• 3D bioprinting., 3D printed equipment, 3D printing techniques, COVID-19 treatment, DOP, EHD, EMP, SLS, drug delivery system, inkjet, personalized medicines, vat photopolymerization,
• MeSH
• 3D tisk * trendy   MeSH
• bioprinting MeSH
• COVID-19 MeSH
• farmaceutický průmysl MeSH
• lidé MeSH
• poskytování zdravotní péče * MeSH
• SARS-CoV-2 MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

PURPOSE: Affinisol HPMC HME is a new popular form of hypromellose specifically designed for the hot melt extrusion and 3D printing of pharmaceutical products. However, reports of its thermal stability include only data obtained under inert N2 atmosphere, which is not consistent with the common pharmaceutical practice. Therefore, detailed investigation of its real-life thermal stability in air is paramount for identification of potential risks and limitations during its high-temperature processing. METHODS: In this work, the Affinisol HPMC HME 15LV powder as well as extruded filaments will be investigated by means of thermogravimetry, differential scanning calorimetry and infrared spectroscopy with respect to its thermal stability. RESULTS: The decomposition in N2 was proceeded in accordance with the literature data and manufacturer's specifications: onset at ~260°C at 0.5°C·min-1, single-step mass loss of 90-95%. However, in laboratory or industrial practice, high-temperature processing is performed in the air, where oxidation-induced degradation drastically changes. The thermogravimetric mass loss in air proceeded in three stages: ~ 5% mass loss with onset at 150°C, ~ 70% mass loss at 200°C, and ~ 15% mass loss at 380°C. Diffusion of O2 into the Affinisol material was identified as the rate-determining step. CONCLUSION: For extrusion temperatures ≥170°C, Affinisol exhibits a significant degree of degradation within the 5 min extruder retention time. Hot melt extrusion of pure Affinisol can be comfortably performed below this temperature. Utilization of plasticizers may be necessary for safe 3D printing.

• Klíčová slova
• DSC, TGA, affinisol, hot melt extrusion, thermal degradation,
• MeSH
• 3D tisk MeSH
• farmaceutická chemie * metody   MeSH
• rozpustnost MeSH
• technologie extruze tavenin * MeSH
• teplota MeSH
• vysoká teplota MeSH
• Publikační typ
• časopisecké články MeSH

The problem of designing tablet geometry and its internal structure that results into a specified release profile of the drug during dissolution was considered. A solution method based on parametric programming, inspired by CAD (computer-aided design) approaches currently used in other fields of engineering, was proposed and demonstrated. The solution of the forward problem using a parametric series of structural motifs was first carried out in order to generate a library of drug release profiles associated with each structural motif. The inverse problem was then solved in three steps: first, the combination of basic structural motifs whose superposition provides the closest approximation of the required drug release profile was found by a linear combination of pre-calculated release profiles. In the next step, the final tablet design was constructed and its dissolution curve found computationally. Finally, the proposed design was 3D printed and its dissolution profile was confirmed experimentally. The computational method was based on the numerical solution of drug diffusion in a boundary layer surrounding the tablet, coupled with erosion of the tablet structure encoded by the phase volume function. The tablets were 3D printed by fused deposition modelling (FDM) from filaments produced by hot-melt extrusion. It was found that the drug release profile could be effectively controlled by modifying the tablet porosity. Custom release profiles were obtained by combining multiple porosity regions in the same tablet. The computational method yielded accurate predictions of the drug release rate for both single- and multi-porosity tablets.

• Klíčová slova
• 3D printing, dissolution, hot-melt extrusion, mathematical modelling, parametric programming,
• MeSH
• 3D tisk * MeSH
• farmaceutická technologie metody   MeSH
• poréznost MeSH
• tablety chemie   farmakokinetika   MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• tablety MeSH

Due to the possibility of designing various spatial structures, three-dimensional printing can be implemented in the production of customized medicines. Nevertheless, the use of these methods for the production of dosage forms requires further optimization, understanding, and development of printouts' quality verification mechanisms. Therefore, the goal of our work was the preparation and advanced characterization of 3D printed orodispersible tablets (ODTs) containing fluconazole, printed by the fused deposition modeling (FDM) method. We prepared and analyzed 7 printable filaments containing from 10% to 70% fluconazole, used as model API. Obtaining a FDM-printable filament with such a high API content makes our work unique. In addition, we confirmed the 12-month stability of the formulation, which, to our knowledge, is the first study of this type. Next, we printed 10 series of porous tablets containing 50 mg of API from both fresh and stored filaments containing 20 %, 40 %, or 70 % fluconazole. We confirmed the high quality and precision of the printouts using scanning electron microscopy. The detailed analysis of the tablets' disintegration process included the Pharmacopeial test, but also the surface dissolution imaging analysis (SDI) and the test simulating oral conditions performed in own-constructed apparatus. For each composition, we obtained tablets disintegrating in less than 3 min, i.e., meeting the criteria for ODTs required by the European Pharmacopeia. The filaments' storage at ambient conditions did not affect the quality of the tablets. All printed tablets released over 95% of the fluconazole within 30 min. Moreover, the printouts were stable for two weeks.

• Klíčová slova
• Fused deposition modeling, High drug loading, Hot-melt extrusion, Orodispersible tablets, Stability, Surface dissolution imaging,
• MeSH
• 3D tisk * MeSH
• farmaceutická technologie metody   MeSH
• flukonazol * MeSH
• poréznost MeSH
• tablety chemie   MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• flukonazol * MeSH
• tablety MeSH

Hydroxypropylmethylcellulose (HPMC), also known as Hypromellose, is a traditional pharmaceutical excipient widely exploited in oral sustained drug release matrix systems. The choice of numerous viscosity grades and molecular weights available from different manufacturers provides a great variability in its physical-chemical properties and is a basis for its broad successful application in pharmaceutical research, development, and manufacturing. The excellent mucoadhesive properties of HPMC predetermine its use in oromucosal delivery systems including mucoadhesive tablets and films. HPMC also possesses desirable properties for formulating amorphous solid dispersions increasing the oral bioavailability of poorly soluble drugs. Printability and electrospinnability of HPMC are promising features for its application in 3D printed drug products and nanofiber-based drug delivery systems. Nanoparticle-based formulations are extensively explored as antigen and protein carriers for the formulation of oral vaccines, and oral delivery of biologicals including insulin, respectively. HPMC, being a traditional pharmaceutical excipient, has an irreplaceable role in the development of new pharmaceutical technologies, and new drug products leading to continuous manufacturing processes, and personalized medicine. This review firstly provides information on the physical-chemical properties of HPMC and a comprehensive overview of its application in traditional oral drug formulations. Secondly, this review focuses on the application of HPMC in modern pharmaceutical technologies including spray drying, hot-melt extrusion, 3D printing, nanoprecipitation and electrospinning leading to the formulation of printlets, nanoparticle-, microparticle-, and nanofiber-based delivery systems for oral and oromucosal application. Hypromellose is an excellent excipient for formulation of classical dosage forms and advanced drug delivery systems. New methods of hypromellose processing include spray draying, hot-melt extrusion, 3D printing, and electrospinning.

• Klíčová slova
• 3D printing, Amorphous solid dispersion, Continuous manufacturing, Controlled release, Matrix tablet, Mucoadhesive formulation,
• MeSH
• deriváty hypromelózy MeSH
• farmaceutická technologie * MeSH
• pomocné látky * MeSH
• příprava léků MeSH
• rozpustnost MeSH
• tablety MeSH
• uvolňování léčiv MeSH
• viskozita MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• deriváty hypromelózy MeSH
• pomocné látky * MeSH
• tablety MeSH

A novel application of the three-dimensional printing technology for the automation of solid phase extraction procedures in a low-pressure sequential injection analysis system is presented. A 3D printed device was used as a housing for nanofiber membranes in solid phase extraction. The applicability of the device is demonstrated with the extraction of substances of various physical-chemical properties. Pharmaceuticals including non-steroidal anti-inflammatory drugs, antihistaminics, and steroidal structures, as well as emerging pollutants such as bisphenols and pesticide metsulfuron methyl were used as model analytes to study the extraction performance of the nanofibers. Six different nanofiber types comprising polyamide, polyethylene, polyvinylidene fluoride, polycaprolactone combined with polyvinylidene fluoride, and polyacrylonitrile, produced by electrospinning were tested in solid phase extraction. The suitability of specific nanofibers for particular analytes is demonstrated.

• Klíčová slova
• Automation, Nanofibers, Pharmaceuticals, Pollutants, Solid phase extraction,
• Publikační typ
• časopisecké články MeSH