Article, 2024

Tailor‐Made Doses of Pharmaceuticals by Tunable Modular Design: A Case Study on Tapering Antidepressant Medication

Advanced Materials, ISSN 1521-4095, 0935-9648, Page e2403852, 10.1002/adma.202403852

Contributors

Ahola, Ilari [1] Raijada, Dhara K [1] [2] Cornett, Claus 0000-0001-6991-5362 [1] Bøtker, Johan Peter [1] Rantanen, Jukka Tapio 0000-0002-8211-5607 [1] Genina, Natalja 0000-0002-9947-6900 (Corresponding author) [1]

Affiliations

  1. [1] University of Copenhagen
  2. [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD];
  3. [2] AstraZeneca (Sweden)
  4. [NORA names: Sweden; Europe, EU; Nordic; OECD]

Abstract

An abrupt cessation of antidepressant medication can be challenging due to the appearance of withdrawal symptoms. A slow hyperbolic tapering of an antidepressant, such as citalopram hydrobromide (CHB), can mitigate the withdrawal syndrome. However, there are no viable dosage forms on the market to implement the tapering scheme. A solution using a tunable modular design (TMD) approach to produce flexible and accurate doses of CHB is proposed. This design consists of two parts: 1) a module with a fixed amount of preloaded CHB in a freeze-dried polymer matrix, and 2) fine-tuning the CHB dose by inkjet printing. A noncontact food-grade printer, used for the first time for printing pharmaceuticals, is modified to allow for accurate printing of the highly concentrated CHB ink on the porous CHB-free or CHB-preloaded modules. The produced modules with submilligram precision are bench-marked with commercially available CHB tablets that are manually divided. The TMD covers the entire range of doses needed for the tapering (0.5-23.8 mg). The greatest variance is 13% and 88% when comparing the TMD and self-tapering, respectively. Self-tapering is proven inaccurate and showcases the need for the TMD to make available accurate and personalized doses to wean off treatment with CHB.

Keywords

TMD, accurate dosing, accurate printing, antidepressant medication, antidepressants, appearance, appearance of withdrawal symptoms, case study, cases, cessation, citalopram, citalopram hydrobromide, design, dosage, dosage forms, dose, doses of pharmaceuticals, form, hydrobromide, ink, inkjet, inkjet printing, market, matrix, medication, modular design, modulation, parts, personalized dosing, pharmaceuticals, polymer, polymer matrix, precision, printing, scheme, self-tapping, solution, study, submilligram, symptoms, syndrome, tablets, taper, tapering scheme, tunability, variance, withdrawal, withdrawal symptoms, withdrawal syndrome

Funders

  • NordForsk
  • University of Copenhagen

Data Provider: Digital Science