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

Abstract

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.

The Expanded Role of Chitosan in Localized Antimicrobial Therapy

“…The vaginal ring containing chitosan and metronidazole obtained a bactericidal effect after 24 h and was found superior. The findings confirmed a synergistic effect of chitosan and metronidazole against E. coli [320].…”

“…Chitosan hydrogel-thickened nanoemulsion containing essential oil expressed antifungal activity in vitro [317] -Chitosan hydrogel significantly reduced biofilm formations both in vitro and in an in vivo model [318] Iminoboronate Fungicidal activity in biomimetic conditions and inhibition of biofilm formation in vitro was obtained [319] Bacterial vaginosis -Low concentration chitosan hydrogel efficiently eradicated Pseudomonas aeruginosa biofilms in vitro [24] Superior in vitro activity against S. aureus and S. epidermidis by chitosan formulated as hydrogel [8] Metronidazole 3D printed vaginal ring containing chitosan and metronidazole obtained a bactericidal effect against E. coli and confirmed synergistic antibacterial effect by chitosan and metronidazole [320] Trichomoniasis Auranofin…”

“…In a recent study, vaginal rings were manufactured using 3D printing [320]. The vaginal rings were filled with polymer-based gels containing antibiotic metronidazole, and their effect was evaluated in vitro against C. albicans and E. coli.…”

Accelerating 3D printing of pharmaceutical products using machine learning

“…Specifically, the simplicity and low cost of FDM 3DP has led to the general view that it may be the technology to be clinically adopted to produce personalized medicines. Enthusiasm towards FDM 3DP amongst pharmaceutical researchers has been demonstrated by its use to manufacture a range of drug delivery devices, including 3D printed tablets (Printlets) ( Bogdahn et al, 2021 ; Figueiredo et al, 2022 ; Isreb et al, 2019 ; Melocchi et al, 2021 ; Oladeji et al, 2022 ; Pereira et al, 2020 ; Shi et al, 2021 ; Tranová et al, 2022 ; Windolf et al, 2022 ), gastro-retentive tablets ( Zhao et al, 2022 ), microneedles ( Wu et al, 2021 ), and patient-specific devices ( Arany et al, 2021 ; Carlier et al, 2021 ; Eleftheriadis and Fatouros, 2021 ; Eleftheriadis et al, 2020 ; Haddow et al, 2021 ; Liang et al, 2018 ; Saviano et al, 2022 ). While interest in pharmaceutical 3DP continues to grow, with pharmaceutical companies such as Aprecia and Triastek investing in the technology, progress is arguably hampered by the empirical process of formulation development ( Elbadawi et al, 2021b ; Seoane-Viaño et al, 2021 ).…”

The Evolution of the 3D-Printed Drug Delivery Systems: A Review

“…(Figure 14.) This article focused on avoiding the loss and decomposition of API through the printing process and manufacturing a drug delivery system, which could be directly and rapidly printed at the bedside or in the pharmacy as individualized medication [178]. The currently available approaches did not consider the specific anatomy of each patient, the patient's medical conditions, age, and gender specificity which limited the effective therapy whereas every patient is unique and should require different doses of drugs and hormones [179].…”