Integration of personalized drug delivery systems into digital health

Raijada, Dhara; Wac, Katarzyna; Greisen, Emanuel; Rantanen, Jukka

doi:10.1016/j.addr.2021.113857

Cited by 68 publications

(46 citation statements)

References 104 publications

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“…The reason for these investigations were to certify the applicability of FDM printing in the field of personalized medication manufacturing. The APIs can be delivered at the right dose locally in the vagina, which provide an excellent response [ 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

Manufacturing and Examination of Vaginal Drug Delivery System by FDM 3D Printing

et al. 2021

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Vaginal drug delivery systems can provide a long-term and constant liberation of the active pharmaceutical ingredient even for months. For our experiment, FDM 3D printing was used to manufacture the vaginal ring samples from thermoplastic polyurethane filament, which enables fast manufacturing of complex, personalized medications. 3D printing can be an excellent alternative instead of industrial manufacturing, which is complicated and time-consuming. In our work, the 3D printed vaginal rings were filled manually with jellified metronidazole or chloramphenicol for the treatment of bacterial vaginosis. The need for manual filling was certified by the thermogravimetric and heatflow assay results. The manufactured samples were analyzed by an Erweka USP type II Dissolution Apparatus, and the dissolution profile can be distinguished based on the applied jellifying agents and the API’s. All samples were considered non-similar based on the pairwise comparison. The biocompatibility properties were determined by prolonged MTT assay on HeLa cells, and the polymer could be considered non-toxic. Based on the microbiological assay on E. coli metronidazole and chitosan containing samples had bactericidal effects while just metronidazole or just chitosan containing samples bacteriostatic effect. None of these samples showed a fungistatic or fungicide effect against C. albicans. Based on our results, we successfully manufactured 3D printed vaginal rings filled with jellified metronidazole.

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Section: Discussionmentioning

confidence: 99%

Manufacturing and Examination of Vaginal Drug Delivery System by FDM 3D Printing

et al. 2021

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“…This could be achieved through smallscale local capsule filling or through the development of on-demand pharmacoprinting based on additive manufacturing (2D/3D) [35][36][37][38], where other means (e.g., colour, taste, shape, release) of age appropriateness can also be used. Key formulation attributes can be managed using a paediatric Quality Target Product Profile [39] and by including unique identifiers, e.g., 2D barcodes, at the individual dosage unit giving an easy access to tailored information regarding the drug product [40]. There is still likely a great need for further development of the pharmacoprinting technique, including formulation science, before it can be realised in the hospital pharmacy.…”

Section: Discussionmentioning

confidence: 99%

Manipulations of Oral Medications in Paediatric Neurology and Oncology Care at a Swedish University Hospital: Health Professionals’ Attitudes and Sources of Information

et al. 2021

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Oral administration of medications to children requires age-appropriate dosage forms and strengths. In this study, we: (i) assessed the extent of oral dosage form manipulations, (ii) documented how it is carried out, and (iii) examined the attitudes and sources of information regarding the handling from healthcare professionals. Prospective reviews of electronic records, ward observations, and clinician surveys were performed at a paediatric neurology ward and a paediatric oncology ward in Sweden during April to May of 2018. Approximately 15% of oral medications were manipulated for the studied patient group (median age 12.9 years in oncology, 5.8 years in neurology) with approximately 30% of the patients having an enteral feeding tube. Manipulations were performed both to obtain an appropriate dose from, for example, a fraction of the original tablet or to obtain a powder that could be used to prepare a slurry for administration through enteral feeding tubes. Risks identified were related to patient safety such as cross contamination, suboptimal absorption/pharmacokinetics and inaccurate dose. When examining the working environment of nurses, we observed safe handling of hazardous substances but the nurses occasionally experienced stress and a fear of making mistakes due to absence of information. Paediatricians experienced a lack of time to search for proper information on manipulations. As a step towards improving safety in paediatric medication, we suggest the introduction of clinical pharmacists into the team and further evaluating the possibilities of using more ready-to-administer medications with necessary product information and pharmacovigilance support.

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“…The printing time was 14.0 ± 0.1 s for one DEEP and 19.2 ± 0.1 s for four DEEP located horizontally in the same row. Hence, the development of printing equipment for pharmaceutical use is needed to allow easier implementation of a new technology for manufacturing drug products that can meet the existing strict quality control requirements [6].…”

Section: Fabrication Of Deepmentioning

confidence: 99%

“…Two subpopulations that are particularly susceptible to the lack of appropriate doses, dosage forms, and drug release kinetics are pediatric and geriatric groups [6]. This is because children and elderly are different, in regards to age and status of health, from the average and healthy "standard" person, whose response to the drug defines the recommended doses [7].…”

Section: Introductionmentioning

confidence: 99%

“…Data-enriched edible pharmaceuticals (DEEP) have been proposed as personalized dosage forms for oral drug delivery, where the patient-tailored dose is printed in the pattern of a unique QR code that encapsulates relevant information [23]. The QR code pattern can be used to ease identification of the dosage form, obtain patient-tailored or dosage form-tailored information (e.g., patient information sheet with embedded videos, regarding the correct administration of drug products) and allow for traceability of the drug product at a single dosage unit level, even if the original package is lost or not available [6]. DEEP was fabricated using an orodispersible formulation, thereby minimizing the swallowing difficulties.…”

Section: Introductionmentioning

confidence: 99%

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Data-Enriched Edible Pharmaceuticals (DEEP) with Bespoke Design, Dose and Drug Release

et al. 2021

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Data-enriched edible pharmaceuticals (DEEP) is an approach to obtain personalized medicine, in terms of flexible and precise drug doses, while at the same time containing data, embedded in quick response (QR) codes at a single dosage unit level. The aim of this study was to fabricate DEEP with a patient-tailored dose, modify drug release and design to meet patients’ preferences. It also aimed to investigate physical stability in terms of the readability of QR code patterns of DEEP during storage. Cannabinoids, namely, cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), were used as the model active pharmaceutical ingredients (APIs). Three different substrates and two colorants for the ink were tested for their suitability to fabricate DEEP by desktop inkjet printing. Flexible doses and customizable designs of DEEP were obtained by manipulating the digital design of the QR code, particularly, by exploring different pattern types, embedded images and the physical size of the QR code pattern. Modification of the release of both APIs from DEEP was achieved by applying a hydroxypropyl cellulose (HPC) polymer coating. The appearance and readability of uncoated and polymer-coated DEEP did not change on storage in cold and dry conditions; however, the HPC polymer layer was insufficient in preserving the readability of the QR code pattern in the extreme storage condition (40 °C and 75% relative humidity). To sum up, the DEEP concept provides opportunities for the personalization of medicines, considering also patients’ preferences.

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Integration of personalized drug delivery systems into digital health

Cited by 68 publications

References 104 publications

Manufacturing and Examination of Vaginal Drug Delivery System by FDM 3D Printing

Manufacturing and Examination of Vaginal Drug Delivery System by FDM 3D Printing

Manipulations of Oral Medications in Paediatric Neurology and Oncology Care at a Swedish University Hospital: Health Professionals’ Attitudes and Sources of Information

Data-Enriched Edible Pharmaceuticals (DEEP) with Bespoke Design, Dose and Drug Release

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