[en] The standard of care for patients with Adrenal Insufficiency (AI) is suboptimal. Administration of hydrocortisone three times a day produces plasma cortisol fluctuations 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 ± 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 ± 2.8 % and the inter-batch standard deviation was ± 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.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Ayyoubi, Sejad; Erasmus University Medical Center, Rotterdam > Department of Hospital Pharmacy
Van Kampen, Eveline; Erasmus University Medical Center, Rotterdam > Department of Hospital Pharmacy
Kocabas, L.I.; UU - University of Utrecht [NL] > Department of Pharmaceutics > Utrecht Institute for Pharmaceutical Sciences,
Parulski, Chloé ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM) ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique ; Université de Liège - ULiège > Faculté de Médecine > Form. doct. sc. biomed. & pharma. (paysage) ; Université de Liège - ULiège > Faculté de Médecine > Doct. scienc. biom. pharma.
Lechanteur, Anna ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM) ; Université de Liège - ULiège > Département de pharmacie
Evrard, Brigitte ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique ; Université de Liège - ULiège > Département de pharmacie ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
De Jager, K.; Erasmus University Medical Center, Rotterdam > Department of Hospital Pharmacy
Muller, E.; The Hague Hospital Pharmacy > Department of Pharmaceutical Quality Control
Wilms, E. W.; The Hague Hospital Pharmacy > Department of Pharmaceutical Quality Control
Meulenhoff, P. W. C.; Tridi Pharma B.V. M.H., Utrecht
Ruijgrok, Elisabeth J.; Erasmus University Medical Center, Rotterdam > Department of Hospital Pharmacy
Language :
English
Title :
3D printed, personalized sustained release cortisol for patients with adrenal insufficiency
Alternative titles :
[fr] Cortisol personnalisé à libération prolongée imprimé en 3D pour les patients souffrant d'insuffisance surrénalienne
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