Fabrication of Chocolate Containing Aripiprazole Using Three-Dimensional Printing Technology
Keywords:
3D Printing, aripiprazole, chocolate, personalized medication, adherence, stabilityAbstract
Background: Three-dimensional (3D) printing technology is now seen as a valuable, efficient, and economical method for producing drugs with unique characteristics, tailored to specific patients with special needs. Aripiprazole is used to treat schizophrenia. Due to the ineffective treatment of aripiprazole in pediatric psychiatric patients, chocolate-based dosage forms of aripiprazole were created using 3D printing technology. These dosage forms are expected to help overcome dose adjustment challenges and medication non-compliance, especially in pediatric psychiatric patients.
Objectives: This study aims to develop a chewable, chocolate-based oral formulation of aripiprazole using 3D printing technology and to establish a method for analyzing aripiprazole in chocolate.
Methods: Aripiprazole was incorporated into chocolate-based dosage forms composed of cocoa powder, cocoa butter, powdered sugar, and lecithin to achieve the desired chocolate properties. The desired solid form was then created using a fused deposition modelling (FDM) 3D printer. Analytical method validation of aripiprazole in chocolate-based dosage forms was performed using ultra-pressure liquid chromatography (UPLC). The stability of aripiprazole after five rounds of re-melting chocolate-based formulations was analyzed and compared with intact aripiprazole in chocolate. The physicochemical properties of aripiprazole in chocolate-based dosage forms were evaluated over 90 days of storage at 30 ± 2°C with 65 ± 5% relative humidity.
Results: The bitter taste of aripiprazole was masked by the chocolate, providing desirable texture, toughness, and taste attributes. The dosage forms could be created in various shapes using 3D printing, maintaining solidification characteristics at room temperature. The analytical method validation showed high accuracy (99.8-109.7%) and precision (0.13-2.56%) for aripiprazole. The remaining amount of aripiprazole in chocolate after five rounds of re-melting and storage for up to 90 days remained within the acceptable range of 95-105%. Furthermore, the physical properties of aripiprazole in chocolate remained unchanged.
Conclusion: This study highlights the potential of 3D printing in fabricating custom-made solid dosage forms of aripiprazole in chocolate for personalized medication. This approach can help reduce medication non-compliance in patients and could be applied to other drugs.
References
Alomari M, Mohamed FH, Basit AW, Gaisford S. Personalised dosing: Printing a dose of one's own medicine. Int J Pharm. 2015;494(2):568-77. doi:10.1016/j.ijpharm.2014.12.006.
National Health Service England. Improving outomes through personalised medicine [Internet]. n.p.: National Health Service England; 2017 [cited 2022 Mar 13]. Available from: https://www.england.nhs.uk/publication/improving-outcomes-through-personalised-medicine/
The Lancet. Personalised medicine in the UK. Lancet. 2018;391(10115):e1. doi: 10.1016/S0140-6736(17)33261-0.
Florence AT, Lee VH. Personalised medicines: more tailored drugs, more tailored delivery. Int J Pharm. 2011;415(1-2):29-33. doi: 10.1016/j.ijpharm.2011.04.047.
Aprecia Pharmaceuticals. First FDA-approved medicine manufactured using 3D printing technology now available [Internet]. Blue Ash (OH): Aprecia Pharmaceuticals; 2016 [cited 2022 Mar 14]. Available from: https://www.aprecia.com/news/first-fda-approved-medicine-manufactured-using-3d-printing-technology-now-available
Semahegn A, Torpey K, Manu A, Assefa N, Tesfaye G, Ankomah A. Psychotropic medication non-adherence and its associated factors among patients with major psychiatric disorders: a systematic review and meta-analysis. Syst Rev 2020;9(1):17. doi: 10.1186/s13643-020-1274-3.
Lacro JP, Dunn LB, Dolder CR, Leckband SG, Jeste DV. Prevalence of and risk factors for medication nonadherence in patients with schizophrenia: a comprehensive review of recent literature. J Clin Psychiatry. 2002;63(10):892-909. doi: 10.4088/jcp.v63n1007.
Higashi K, Medic G, Littlewood KJ, Diez T, Granström O, De Hert M. Medication adherence in schizophrenia: factors influencing adherence and consequences of nonadherence, a systematic literature review. Ther Adv Psychopharmacol. 2013;3(4):200-18. doi: 10.1177/2045125312474019.
Sun SX, Liu GG, Christensen DB, Fu AZ. Review and analysis of hospitalization costs associated with antipsychotic nonadherence in the treatment of schizophrenia in the United States. Curr Med Res Opin. 2007;23(10):2305-12. doi: 10.1185/030079907X226050.
Hack S, Chow B. Pediatric psychotropic medication compliance: a literature review and research-based suggestions for improving treatment compliance. J Child Adolesc Psychopharmacol. 2001;11(1):59-67. doi: 10.1089/104454601750143465.
Jamróz W, Kurek M, Łyszczarz E, Szafraniec J, Knapik-Kowalczuk J, Syrek K, et al. 3D printed orodispersible films with aripiprazole. Int J Pharm. 2017;533(2):413-20. doi: 10.1016/j.ijpharm.2017.05.052.
Lee JH, Park C, Song IO, Lee BJ, Kang CY, Park JB. Investigation of patient-centric 3D-printed orodispersible films containing amorphous aripiprazole. Pharmaceuticals (Basel) 2022;15(7):895. doi: 10.3390/ph15070895.
Uchida S, Tanaka S, Seki S, Nakajima S, Kamiya C, Hakamata A, et al., editors. Evaluation of palatability of cocoa-flavored gummi drug of aripiprazole developed from commercially available tablets. Proceedings for annual meeting of The Japanese Pharmacological Society WCP2018 (The 18th world congress of basic and clinical pharmacology); 2018 Jul 1-6; Kyoto, Japan. Japanese Pharmacological Society; 2018.
Karyappa R, Hashimoto M. Chocolate-based ink three-dimensional printing (Ci3DP). Sci Rep. 2019;9(1):14178. doi: 10.1038/s41598-019-50583-5.
ChemSpider. Aripiprazole [Internet]. London: Royal Society of Chemistry; 2021 [cited 2021 Jan 19]. Available from: http://www.chemspider.com/Chemical-Structure.54790.html?rid=393cd0eb-c832-48a4-9c20-78d464f4c5a0
Staiger B. Cocoa - Abilify (Aripiprazole) interaction [Internet]. Ithaca (NY): HelloPharmacist; 2023 [cited 2023 Nov 23]. Available from: https://hellopharmacist.com/drug-herbal-interactions/cocoa-with-aripiprazole/
Afoakwa EO. Structure – properties (rheology, texture and melting) relationships in chocolate manufacture. Chocolate science and technology. Hoboken (NJ): John Wiley & Sons; 2016. p. 101-54.
Beckett ST. Controlling the flow properties of liquid chocolate. The science of chocolate. 2nd ed. London: Royal Society of Chemistry; 2019. p. 80-102.
Masoumi HR, Basri M, Samiun WS, Izadiyan Z, Lim CJ. Enhancement of encapsulation efficiency of nanoemulsion-containing aripiprazole for the treatment of schizophrenia using mixture experimental design. Int J Nanomedicine. 2015;10:6469-76. doi: 10.2147/IJN.S89364.
Canty DJ, Zeisel SH. Lecithin and choline in human health and disease. Nutr Rev 1994;52(10):327-39. doi: 10.1111/j.1753-4887.1994.tb01357.x.
Zeisel SH. A brief history of choline. Ann Nutr Metab. 2012;61(3):254-8. doi: 10.1159/000343120.
Krol S. Challenges in drug delivery to the brain: nature is against us. J Control Release. 2012;164(2):145-55. doi: 10.1016/j.jconrel.2012.04.044.
Shinde S. Identification & assay methods for aripiprazole, aripiprazole USP monograph methods overview [Internet]. Darmstadt (Germany): Merck KGaA; 2017 [cited 2022 Apr 20]. Available from: https://www.sigmaaldrich.com/TH/en/technical-documents/protocol/analytical-chemistry/small-molecule-hplc/aripiprazole
The International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use (ICH). Validation of analytical procedures Q2(R2). n.p.: U.S. Department of Health and Human Services Food and Drug Administration; 2022 (updated Aug 29 2022) [cited 2022 Nov 21]. Available from https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q2r2-validation-analytical-procedures
The International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use (ICH). Stability testing of new drug substances and products Q1A(R2). Amsterdam: European Medicines Agency; 2022 (updated Aug 29 2022) [cited 2022 Nov 21]. Available from https://www.ema.europa.eu/en/ich-q1a-r2-stability-testing-new-drug-substances-drug-products-scientific-guideline
Medina-Mendoza M, Rodriguez-Pérez RJ, Rojas-Ocampo E, Torrejón-Valqui L, Fernández-Jeri AB, Idrogo-Vásquez G, et al. Rheological, bioactive properties and sensory preferences of dark chocolates with partial incorporation of Sacha Inchi (Plukenetia volubilis L.) oil. Heliyon. 2021;7(2):e06154. doi: 10.1016/j.heliyon.2021.e06154.
Żyżelewicz D, Budryn G, Oracz J, Antolak H, Kręgiel D, Kaczmarska M. The effect on bioactive components and characteristics of chocolate by functionalization with raw cocoa beans. Food Res Int. 2018;113:234-44. doi: 10.1016/j.foodres.2018.07.017.
Xometry Europe. Fused deposition modeling (FDM) 3D printing technology overview [Internet]. North Bethesda (MD): Xometry; 2023 [cited 2024 Sep 15]. Available from: https://xometry.pro/en-uk/articles/3d-printing-fdm-overview/
Lipton JI. Printable food: the technology and its application in human health. Curr Opin Biotechnol. 2017;44:198-201. doi: 10.1016/j.copbio.2016.11.015.
Godoi FC, Prakash S, Bhandari BR. 3d printing technologies applied for food design: status and prospects. J Food Eng. 2016;179:44-54. doi: 10.1016/j.jfoodeng.2016.01.025.
Kim SM, Woo JH, Kim HW, Park HJ. Formulation and evaluation of cold-extruded chocolate ganache for three-dimensional food printing. J Food Eng. 2022;314:110785. doi: 10.1016/j.jfoodeng.2021.110785.
United States Pharmacopeia (2024). General chapter, <1225> Validation of compendial procedures. In: USP–NF 2024. Rockville (MD): United States Pharmacopeia Convention; 2024. doi: 10.31003/USPNF_M99945_04_01
Association of Southeast Asian Nations (ASEAN). ASEAN guidelines for validation of analytical procedures [Internet]. n.p.: ASEAN; 2012 [cited 2022 Nov 25]. Available from: https://asean.org/wp-content/uploads/2012/10/Asean-Analytical-Validation-gl.pdf
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Health Administration Division, Office of the Permanent Secretary, Ministry of Public Health and The Society of Hospital Pharmacist, Ministry of Public Health
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
ข้อความภายในบทความที่ตีพิมพ์ในวารสารเภสัชกรรมคลินิกทั้งหมด รวมถึงรูปภาพประกอบ ตาราง เป็นลิขสิทธิ์ของกองบริหารการสาธารณสุข สำนักงานปลัดกระทรวงสาธารณสุข และ ชมรมเภสัชกรโรงพยาบาลกระทรวงสาธารณสุข การนำเนื้อหา ข้อความหรือข้อคิดเห็น รูปภาพ ตาราง ของบทความไปจัดพิมพ์เผยแพร่ในรูปแบบต่าง ๆ เพื่อใช้ประโยชน์ในเชิงพาณิชย์ ต้องได้รับอนุญาตจากกองบรรณาธิการวารสารเภสัชกรรมคลินิกอย่างเป็นลายลักษณ์อักษร
กองบริหารการสาธารณสุข สำนักงานปลัดกระทรวงสาธารณสุข และ ชมรมเภสัชกรโรงพยาบาลกระทรวงสาธารณสุข อนุญาตให้สามารถนำไฟล์บทความไปใช้ประโยชน์และเผยแพร่ต่อได้ โดยอยู่ภายใต้เงื่อนไขสัญญาอนุญาตครีเอทีฟคอมมอน (Creative Commons License: CC) โดย ต้องแสดงที่มาจากวารสาร – ไม่ใช้เพื่อการค้า – ห้ามแก้ไขดัดแปลง, Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
ข้อความที่ปรากฏในบทความในวารสารเป็นความคิดเห็นส่วนตัวของผู้เขียนแต่ละท่านไม่เกี่ยวข้องกับกองบริหารการสาธารณสุข สำนักงานปลัดกระทรวงสาธารณสุข และ ชมรมเภสัชกรโรงพยาบาลกระทรวงสาธารณสุข และบุคลากรในกองฯ หรือ ชมรมฯ แต่อย่างใด ความรับผิดชอบองค์ประกอบทั้งหมดของบทความแต่ละเรื่องเป็นของผู้เขียนแต่ละท่าน หากมีความผิดพลาดใด ๆ ผู้เขียนแต่ละท่านจะรับผิดชอบบทความของตนเอง ตลอดจนความรับผิดชอบด้านเนื้อหาและการตรวจร่างบทความเป็นของผู้เขียน ไม่เกี่ยวข้องกับกองบรรณาธิการ
