Unit:
Department of PharmacyLibrary of the School of Science
Dissertation committee:
Dimitios M. Rekkas, Professor of Pharmaceutical Technology, Section of Pharmaceutical Technology, Department of Pharmacy, National & Kapodistrian University of Athens (Supervisor).
Georgia Valsami, Professor of Biopharmaceutics-Pharmacokinetics, Section of Pharmaceutical Technology, Department of Pharmacy, National & Kapodistrian University of Athens.
Panorios Benardos, Assistant Professor, Section of Manufacturing Technology, School of Mechanical Engineering, National Technical University of Athens.
Ruggero Bettini, Professor of Pharmaceutical Technology, Department of Food and Drugs, University of Parma, Italy.
Paraskevas Dallas, Assistant Professor of Pharmaceutical Technology, Section of Pharmaceutical Technology, Department of Pharmacy, National & Kapodistrian University of Athens.
Sophia Antimisiaris, Professor of Pharmaceutical Technology, Section of Pharmaceutical Technology and Analysis, Department of Pharmacy, University of Patras.
Ioannis Nikolakakis, Professor of Pharmaceutical Technology, Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki.
Original Title:
Application of 3D Printing and Design of Experiments for the Development of Pharmaceutical Products
Translated title:
Application of 3D Printing and Design of Experiments for the Development of Pharmaceutical Products
Summary:
Almost all developed pharmaceutical products are placed on the market into a particular dose that fits the average of the population. Characteristics such as age, race, sex, or weight that can lead to variability in the therapeutic effect are not taken into consideration. This “one-size fits all” approach is not suitable for all, especially in the cases of pediatric populations or dosage forms with narrow therapeutic index. Thus, the field of precision medicines, which allows each individual patient to be prescribed with customized dosages and tailored release profiles of suitable pharmaceutical forms is gaining ground.
Pharmaceutical compounding is a methodology followed by the pharmacists in order to produce personalized medicines in pharmacies. However, the quality of the preparation is based on the pharmacist’s professional education, professional license, and licensing of the pharmacy’s premises. Furthermore, the preparation of galenic products in pharmacies is not harmonized throughout at least the European countries. In contrast to the marketed products, galenic preparations are not tested for their effectiveness, safety, and production method as well as for the validation and cleaning of the equipment or their proper labeling and disposal. Therefore, there are deficiencies in the quality control and assurance of these products.
From all the above it is obvious that the prevailing approach so far has many serious disadvantages in terms of its application in the production of personalized medicinal products, especially when using pharmacologically active substances in low doses with a narrow therapeutic range in groups of patients such as children.
A technology such as 3D printing can potentially overcome these challenges and be a tool allowing easy, flexible, low cost and rapid modification of the dose and release of the active pharmaceutical ingredient according to the patient’s needs and can offer the desired therapeutic effect, at the point of need and at the time of need. By simply varying basic parameters in the digital design, product customization can be achieved without the need for complex manufacturing equipment and processes.
The main goal of this project was to demonstrate the applicability of 3D printing technology in the pharmaceutical field for the production of personalized dosage forms at the point of need and when in need, while assuring product quality. The combination of Pharma 4.0 technologies such as 3D printing and Machine Vision, analytical techniques, and Quality by Design showed that precision medicines can be manufactured on demand and at the same time assuring both quality and traceability during the whole production process.
The experimental scheme consisted of firstly employing the 3D Printing technology for the partial coating of matrix tablets with glycerides, where the active ingredient release would be precisely regulated by controlling the coating characteristics only, without modifying the core formulation. The feasibility of the proposed technology was shown by modifying the geometry of the coating and acquiring knowledge on which of these parameters and/or their interactions affect the release profile of the active ingredient and thus achieving personalized drug release rates according to the patient’s needs.
E. Tsintavi, PhD Thesis, Athens 2022 | vi
Secondly, a reliable, flexible, cost-effective and most of all patient-centered system to assure quality when preparing pharmaceutical products in pharmacies and thus mitigating the risks associated with healthcare-medication errors has been developed. The system designed is in line with the most recent regulatory directives incorporating Industry 4.0 key enabling technologies and enables the production of personalized medicinal products at the point of need with the use of 3D Printing, while a combined Deep Neural Network based Machine Vision system and analytical methodology assure both quality and traceability during the whole production process.
The results revealed that 3D printing technology could be employed for addressing the challenges associated with the production of personalized medicine. Through 3D printing flexibility, cost effectiveness, robustness, versatility, precision, and speed, new possibilities to product development and manufacturing were possible.
Main subject category:
Science
Other subject categories:
Health Sciences
Keywords:
Three-Dimensional Printing, Pharma 4.0, Personalized medicine, Quality by Design, Pharmaceutical Compounding, Deep Neural Networks, Machine Vision
Number of references:
210
File:
File access is restricted until 2024-06-13.
PhD Thesis Eleni Tsintavi.pdf
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File access is restricted until 2024-06-13.
