Design and development of personalized dosage forms by printing technology
Palo, Mirja (2017-06-16)
Palo, Mirja
Åbo Akademi - Åbo Akademi University
16.06.2017
Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
Julkaisun pysyvä osoite on
https://urn.fi/URN:ISBN:978-952-12-3558-0
https://urn.fi/URN:ISBN:978-952-12-3558-0
Tiivistelmä
The development of tailored dosage forms provides a wide range of possibilities for meeting the needs of individual drug therapy. The personalized dosage forms improve the safety of drug treatment by decreasing the risk of overdosing and adverse reactions. Conventional drug preparations with fixed dose strengths are generally produced in large industrial scale. However, the tailored dosage forms for individual patients could be manufactured in small batches with specific materials, drug content and release profile. Therefore, alternative fabrication methods, such as printing technology, are being investigated for the customization of the dosage forms. Printing technology is a flexible method for the on-demand production of drug preparations with variable doses at the point-of-care.
The thesis was aimed at investigating the feasibility of two-dimensional (2D) printing technology for the fabrication of personalized dosage forms. In the 2D printed dosage forms, a pharmaceutical ink is typically deposited and solidified on a planar carrier substrate according to a predefined pattern. The dosing accuracy and reproducibility of the inkjet-printed formulations could be controlled on the single droplet scale. Furthermore, tailoring the properties and the composition of the formulations allows obtaining drug delivery systems (DDS) with controlled drug release profiles and/or with multiple active pharmaceutical ingredients (APIs).
The versatility of 2D printing technology was demonstrated by preparing printed formulations either by inkjet or flexographic printing on planar edible substrates with different types of pharmaceutical inks. The printed formulations and their components were analyzed to allocate the crucial aspects in the development process and to improve the knowledge about the physicochemical properties, in vitro performance and stability of the printed APIs. The printability of the inks and the specific printing parameters were closely related to the rheological properties of the drug solutions. The solid state of the printed APIs was dependent on the ink composition, the ink incorporation capacity of the substrates, and the physicochemical properties of the APIs. Solid state analysis of the final dosage forms showed that the APIs were distributed uniformly in a crystalline or molecularly dispersed state. Furthermore, the flexographically prepared solid nanoparticulate systems exhibited an enhanced in vitro drug release due to the spatial distribution of the crystalline nanosuspension inks.
The high dosing precision of the inkjet printing process was ensured by the stable jetting of the drug solutions. However, the dosing of nanosuspensions by flexographic imprinting was less accurate mainly because of the format of the ink transfer system. The dosing flexibility of the inkjet-printed pharmaceuticals could be regulated by adjusting the printing resolution or the physical size of the dosage units. Furthermore, the implementation of non-destructive attenuated total reflectance Fourier transform infrared spectroscopy with multivariate data analysis showed high applicability for the quantification of printed pharmaceuticals. In addition to edible commercial substrates, the suitability of gelatin-based electrospun fiber matrices as carrier substrates for the fabrication of printed dosage forms was studied. Moreover, drug-loaded electrospun fiber mats were produced by stabilizing the amorphous state of a poorly water-soluble drug within the inner structure of these fibers. The use of drug-loaded fibrous substrates presented a unique approach for the preparation of dual DDS, where an API was inkjet-printed on the drug-loaded matrices that contained another API. The analysis of the designed combination DDS showed that both drugs exhibited an independent release behavior.
The thesis presents an extensive overview on the main aspects of the development of personalized dosage forms by 2D printing technology. The research improves the understanding of the key factors for successful tailoring and manufacturing of the printed dosage forms, elaborates on the quality control aspects of the printing process, and provides an insight into the essential properties and the performance of the printed pharmaceuticals.
The thesis was aimed at investigating the feasibility of two-dimensional (2D) printing technology for the fabrication of personalized dosage forms. In the 2D printed dosage forms, a pharmaceutical ink is typically deposited and solidified on a planar carrier substrate according to a predefined pattern. The dosing accuracy and reproducibility of the inkjet-printed formulations could be controlled on the single droplet scale. Furthermore, tailoring the properties and the composition of the formulations allows obtaining drug delivery systems (DDS) with controlled drug release profiles and/or with multiple active pharmaceutical ingredients (APIs).
The versatility of 2D printing technology was demonstrated by preparing printed formulations either by inkjet or flexographic printing on planar edible substrates with different types of pharmaceutical inks. The printed formulations and their components were analyzed to allocate the crucial aspects in the development process and to improve the knowledge about the physicochemical properties, in vitro performance and stability of the printed APIs. The printability of the inks and the specific printing parameters were closely related to the rheological properties of the drug solutions. The solid state of the printed APIs was dependent on the ink composition, the ink incorporation capacity of the substrates, and the physicochemical properties of the APIs. Solid state analysis of the final dosage forms showed that the APIs were distributed uniformly in a crystalline or molecularly dispersed state. Furthermore, the flexographically prepared solid nanoparticulate systems exhibited an enhanced in vitro drug release due to the spatial distribution of the crystalline nanosuspension inks.
The high dosing precision of the inkjet printing process was ensured by the stable jetting of the drug solutions. However, the dosing of nanosuspensions by flexographic imprinting was less accurate mainly because of the format of the ink transfer system. The dosing flexibility of the inkjet-printed pharmaceuticals could be regulated by adjusting the printing resolution or the physical size of the dosage units. Furthermore, the implementation of non-destructive attenuated total reflectance Fourier transform infrared spectroscopy with multivariate data analysis showed high applicability for the quantification of printed pharmaceuticals. In addition to edible commercial substrates, the suitability of gelatin-based electrospun fiber matrices as carrier substrates for the fabrication of printed dosage forms was studied. Moreover, drug-loaded electrospun fiber mats were produced by stabilizing the amorphous state of a poorly water-soluble drug within the inner structure of these fibers. The use of drug-loaded fibrous substrates presented a unique approach for the preparation of dual DDS, where an API was inkjet-printed on the drug-loaded matrices that contained another API. The analysis of the designed combination DDS showed that both drugs exhibited an independent release behavior.
The thesis presents an extensive overview on the main aspects of the development of personalized dosage forms by 2D printing technology. The research improves the understanding of the key factors for successful tailoring and manufacturing of the printed dosage forms, elaborates on the quality control aspects of the printing process, and provides an insight into the essential properties and the performance of the printed pharmaceuticals.
Kokoelmat
- 317 Farmasia [19]