The simplicity of object shape and composition modification make additive manufacturing a great option for customized dosage form production. To achieve this goal, the correlation between structural and functional attributes of the printed objects needs to be analyzed. So far, it has not been deeply investigated in 3D printing-related papers. The aim of our study was to modify the functionalities of printed tablets containing liquid crystal-forming drug itraconazole by introducing polyvinylpyrrolidone-based polymers into the filament-forming matrices composed predominantly of poly(vinyl alcohol). The effect of the molecular reorganization of the drug and improved tablets’ disintegration was analyzed in terms of itraconazole dissolution. Micro-computed tomography was applied to analyze how the design of a printed object (in this case, a degree of an infill) affects its reproducibility during printing. It was also used to analyze the structure of the printed dosage forms. The results indicated that the improved disintegration obtained due to the use of Kollidon®CL-M was more beneficial for the dissolution of itraconazole than the molecular rearrangement and liquid crystal phase transitions. The lower infill density favored faster dissolution of the drug from printed tablets. However, it negatively affected the reproducibility of the 3D printed object.
The flexibility of dose and dosage forms makes 3D printing a very interesting tool for personalized medicine, with fused deposition modeling being the most promising and intensively developed method. In our research, we analyzed how various types of disintegrants and drug loading in poly(vinyl alcohol)-based filaments affect their mechanical properties and printability. We also assessed the effect of drug dosage and tablet spatial structure on the dissolution profiles. Given that the development of a method that allows the production of dosage forms with different properties from a single drug-loaded filament is desirable, we developed a method of printing ketoprofen tablets with different dose and dissolution profiles from a single feedstock filament. We optimized the filament preparation by hot-melt extrusion and characterized them. Then, we printed single, bi-, and tri-layer tablets varying with dose, infill density, internal structure, and composition. We analyzed the reproducibility of a spatial structure, phase, and degree of molecular order of ketoprofen in the tablets, and the dissolution profiles. We have printed tablets with immediate- and sustained-release characteristics using one drug-loaded filament, which demonstrates that a single filament can serve as a versatile source for the manufacturing of tablets exhibiting various release characteristics.
Additive technologies have undoubtedly become one of the most intensively developing manufacturing methods in recent years. Among the numerous applications, the interest in 3D printing also includes its application in pharmacy for production of small batches of personalized drugs. For this reason, we conducted multi-stage pre-formulation studies to optimize the process of manufacturing solid dosage forms by photopolymerization with visible light. Based on tests planned and executed according to the design of the experiment (DoE), we selected the optimal quantitative composition of photocurable resin made of PEG 400, PEGDA MW 575, water, and riboflavin, a non-toxic photoinitiator. In subsequent stages, we adjusted the printer set-up and process parameters. Moreover, we assessed the influence of the co-initiators ascorbic acid or triethanolamine on the resin’s polymerization process. Next, based on an optimized formulation, we printed and analyzed drug-loaded tablets containing mebeverine hydrochloride, characterized by a gradual release of active pharmaceutical ingredient (API), reaching 80% after 6 h. We proved the possibility of reusing the drug-loaded resin that was not hardened during printing and determined the linear correlation between the volume of the designed tablets and the amount of API, confirming the possibility of printing personalized modified-release tablets.
Additive manufacturing technologies are considered as a potential way to support individualized pharmacotherapy due to the possibility of the production of small batches of customized tablets characterized by complex structures. We designed five different shapes and analyzed the effect of the surface/mass ratio, the influence of excipients, and storage conditions on the disintegration time of tablets printed using the fused deposition modeling method. As model pharmaceutical active ingredients (APIs), we used paracetamol and domperidone, characterized by different thermal properties, classified into the various Biopharmaceutical Classification System groups. We found that the high surface/mass ratio of the designed tablet shapes together with the addition of mannitol and controlled humidity storage conditions turned out to be crucial for fast tablet’s disintegration. As a result, mean disintegration time was reduced from 5 min 46 s to 2 min 22 s, and from 11 min 43 s to 2 min 25 s for paracetamol- and domperidone-loaded tablets, respectively, fulfilling the European Pharmacopeia requirement for orodispersible tablets (ODTs). The tablet’s immediate release characteristics were confirmed during the dissolution study: over 80% of APIs were released from printlets within 15 min. Thus, this study proved the possibility of using fused deposition modeling for the preparation of ODTs.
Printing technologies in pharmaceutical compounding as a new perspective for hospital pharmacy • The possibility of preparing drugs based on two-and three-dimensional printing technologies have recently been explored in the pharmaceutical field. Possibility of implementation of printing techniques in the preparation of compounded drugs, especially in a hospital pharmacy, was the object of this review. Printing technologies allow production of complex drug products in a single process. Therefore, this technology can become an innovative method preparation of compounded drugs adapted to patients with special therapeutic needs.
Techniki przyrostowe, a szczególnie metody oparte na osadzaniu termoplastycznego tworzywa takie jak Fused deposition modeling (FDM), zyskują coraz liczniejsze zastosowania. Ze względu na dużą różnorodność stosowanych materiałów i szybką możliwość wytworzenia niewielkich partii produktów zgodnie z opracowanym projektem komputerowym, proponowane są jako metoda wytwarzania produktów leczniczych zarówno na skalę przemysłową, jak i małych serii leków. Liczne badania naukowe związane z tą tematyką dotyczą druku postaci leku o różnej formie i strukturze zarówno podania doustnego, takich jak np. tabletki i kapsułki o modyfikowanym i niemodyfikowanym uwalnianiu substancji leczniczej, a także do oka lub na rany. W przypadku metody FDM proces druku poprzedzony jest etapem przygotowania materiału. Polega on na wytworzeniu na drodze ekstruzji topliwej filamentu w formie żyłki. Po wprowadzeniu do głowicy drukarki ulega on ponownemu ogrzaniu, upłynnieniu i precyzyjnemu naniesieniu na stolik roboczy drukarki, w celu wytworzenia struktury przestrzennej zgodnej z projektem komputerowym. Filamenty stosowane w procesie druku postaci leku powinny charakteryzować się m.in. odpowiednią wytrzymałością mechaniczną, powtarzalnością średnicy, a także długoterminową stabilnością. Do składu mieszaniny poddawanej ekstruzji oprócz termoplastycznych polimerów stosowane są również inne substancje pomocnicze, tj. rozsadzające, plastyfikatory oraz hamujące zachodzenie przemian fazowych substancji leczniczej w matrycy polimerowej. Drukowane postacie leku charakteryzują się często zróżnicowaną wewnętrzną strukturą przestrzenną. Z tego względu szybkość uwalniania substancji leczniczej zależy nie tylko od właściwości składników opracowywanego preparatu, ale zwłaszcza od jego pola powierzchni i porowatości oraz kształtu i stopnia wypełnienia. Ponadto poprzez regulację parametrów procesów ekstruzji i drukowania, substancja lecznicza może ulegać rozpuszczeniu w nośniku polimerowym a tym samym następuje zwiększenie jej szybkości rozpuszczania.
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