3D printed, personalized sustained release cortisol for patients with adrenal insufficiency

被引:20
作者
Ayyoubi, S. [1 ]
van Kampen, E. E. M. [1 ]
Kocabas, L. I. [2 ]
Parulski, C. [3 ]
Lechanteur, A. [3 ]
Evrard, B. [3 ]
De Jager, K. [1 ]
Muller, E. [4 ]
Wilms, E. W. [4 ]
Meulenhoff, P. W. C. [5 ]
Ruijgrok, E. J. [1 ]
机构
[1] Erasmus MC, Dept Hosp Pharm, Dr Molewaterpl 40, NL-3015 GD Rotterdam, Netherlands
[2] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Dept Pharmaceut, Utrecht, Netherlands
[3] Univ Liege ULiege, Ctr Interdisciplinary Res Med CIRM, Dept Pharm, Lab Pharmaceut Technol & Biopharm, Ave Hippocrate 15, B-4000 Liege, Belgium
[4] Hague Hosp Pharm, Dept Pharmaceut Qual Control, Charlotte Jacobslaan 70, NL-2545 AB The Hague, Netherlands
[5] Tridi Pharma BV, MH Trompstr 7, NL-3572 XS Utrecht, Netherlands
关键词
MELT-EXTRUSION; DRUG-DELIVERY; HYDROCORTISONE; STRONGER; DOSAGE;
D O I
10.1016/j.ijpharm.2022.122466
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The standard of care for patients with Adrenal Insufficiency (AI) is suboptimal. Administration of hydrocortisone three times a day produces plasma cortisol fluc-tuations associated with negative health outcomes. Furthermore, there is a high inter-individual variability in cortisol need, necessitating a personalized approach. It is hypothesized that a personalized, sustained release formulation would enhance the pharmacotherapy by mimicking the physiological cortisol plasma concentration at a higher level. Therefore, a novel 24 h sustained release 3D printed (3DP) hydrocortisone formulation has been developed (M3DICORT) by coupling hot-melt extrusion with fused deposition modeling. A uniform drug distribution in the 3DP tablets is demonstrated by a content of 101.66 & PLUSMN; 1.60 % with an acceptance value of 4.01. Furthermore, tablets had a stable 24 h dissolution profile where the intra-batch standard deviation was & PLUSMN; 2.8 % and the inter-batch standard deviation was & PLUSMN; 6.8 %. Tablet height and hydrocortisone content were correlated (R2 = 0.996), providing a tool for easy dose personalization. Tablets maintained critical quality attributes, such as dissolution profile (f2 > 60) and content uniformity after process transfer from a single-screw extruder to a twin-screw extruder. Impurities were observed in the final product which should be mitigated before clinical assessment. To our knowledge, M3DICORT is the first 3DP hydrocortisone formulation specifically developed for AI.
引用
收藏
页数:13
相关论文
共 59 条
[1]   Additive Manufacturing of Oral Tablets: Technologies, Materials and Printed Tablets [J].
Abaci, Alperen ;
Gedeon, Christina ;
Kuna, Anna ;
Guvendiren, Murat .
PHARMACEUTICS, 2021, 13 (02) :1-27
[2]  
Alice Konta Andrea, 2017, Bioengineering-Basel, V4, P79, DOI 10.3390/bioengineering4040079
[3]   Quality of life in patients with adrenal insufficiency correlates stronger with hydrocortisone dosage, than with long-term systemic cortisol levels [J].
Andela, Cornelie D. ;
Staufenbiel, Sabine M. ;
Joustra, Sjoerd D. ;
Pereira, Alberto M. ;
van Rossum, Elisabeth F. C. ;
Biermasz, Nienke R. .
PSYCHONEUROENDOCRINOLOGY, 2016, 72 :80-86
[4]  
[Anonymous], 2006, INT C HARMONISATION
[5]  
[Anonymous], 2022, European Pharmacopoeia, V11th
[6]  
[Anonymous], 2022, SUMMMARY PRODUCT CHA
[7]   Stability-indicating HPLC-DAD assay for simultaneous quantification of hydrocortisone 21 acetate, dexamethasone, and fluocinolone acetonide in cosmetics [J].
Arif, Saira ;
Ata, Sadia .
OPEN CHEMISTRY, 2020, 18 (01) :962-973
[8]   3D printed spherical mini-tablets: Geometry versus composition effects in controlling dissolution from personalised solid dosage forms [J].
Ayyoubi, Sejad ;
Cerda, Jose R. ;
Fernandez-Garcia, Raquel ;
Knief, Peter ;
Lalatsa, Aikaterini ;
Healy, Anne Marie ;
Serrano, Dolores R. .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2021, 597
[9]   3D printing of immediate-release tablets containing olanzapine by filaments extrusion [J].
Bhatt, Ukti ;
Malakar, Tushar Kanti ;
Murty, Upadhyayula Suryanarayana ;
Banerjee, Subham .
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, 2021, 47 (08) :1200-1208
[10]   Can children swallow tablets? Outcome data from a feasibility study to assess the acceptability of different-sized placebo tablets in children (creating acceptable tablets (CAT)) [J].
Bracken, Louise ;
McDonough, Emma ;
Ashleigh, Samantha ;
Wilson, Fiona ;
Shakeshaft, Joanne ;
Ohia, Udeme ;
Mistry, Punam ;
Jones, Huw ;
Kanji, Nazim ;
Liu, Fang ;
Peak, Matthew .
BMJ OPEN, 2020, 10 (10)