Formulation and Characterisation of Carbamazepine Orodispersible 3D-Printed Mini-Tablets for Paediatric Use

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2023 Jan 21

PMID 36678881

Authors

Jiayu Hu

Rawan Fitaihi

Shorooq Abukhamees

Hend E Abdelhakim

Affiliations

Soon will be listed here.

Abstract

One of the main challenges to paediatric drug administration is swallowing difficulties, hindering the acceptability of the medicine and hence clinical outcomes. This study aims at developing a child-appropriate dosage form, the orodispersible mini-tablet (ODMT), using the model drug carbamazepine (CBZ). This dosage form was prepared and 3D-printed via a semi-solid extrusion technique. Design of Experiment methods were applied for optimising the formulation. The formulation with 40% (/) of SSG (superdisintegrant) and 5% (/) of PVP K30 (binder) was selected and loaded with CBZ. The drug-loaded tablets were characterised by a mean hardness of 18.5 N and a disintegrating time of 84 s, along with acceptable friability. The mean drug loading ratio of the tablets was tested as 90.56%, and the drug release rate in 0.1 M HCl reached 68.3% at 45 min. Excipients showed proper compatibility with the drug in physical form analysis. Taste assessment via an E-tongue was also conducted, where the drug did not show bitter taste signals at a low concentration in the taste assessment, and the sweetener also blocked bitterness signals in the testing. To this end, ODMTs were found to be potential candidates for child-appropriate dosage forms delivering CBZ.

Citing Articles

From design to 3D printing: A proof-of-concept study for multiple unit particle systems (MUPS) printed by dual extrusion fused filament fabrication.

Oldfield L, Mentrup A, Klinken-Uth S, Auel T, Seidlitz A Int J Pharm X. 2024; 8:100299.

PMID: 39553785 PMC: 11567944. DOI: 10.1016/j.ijpx.2024.100299.

Real-World Evidence of 3D Printing of Personalised Paediatric Medicines and Evaluating Its Potential in Children with Cancer: A Scoping Review.

Ahmed M, Tomlin S, Tuleu C, Garfield S Pharmaceutics. 2024; 16(9).

PMID: 39339248 PMC: 11434924. DOI: 10.3390/pharmaceutics16091212.

Utilization of the Drug-Polymer Solid Dispersion Obtained by Ball Milling as a Taste Masking Method in the Development of Orodispersible Minitablets with Hydrocortisone in Pediatric Doses.

Trofimiuk M, Olechno K, Trofimiuk E, Czajkowska-Kosnik A, Ciosek-Skibinska P, Glowacz K Pharmaceutics. 2024; 16(8).

PMID: 39204386 PMC: 11359562. DOI: 10.3390/pharmaceutics16081041.

Taste Sensor Assessment of Bitterness in Medicines: Overview and Recent Topics.

Uchida T Sensors (Basel). 2024; 24(15).

PMID: 39123846 PMC: 11314865. DOI: 10.3390/s24154799.

Critical View on the Qualification of Electronic Tongues Regarding Their Performance in the Development of Peroral Drug Formulations with Bitter Ingredients.

Steiner D, Meyer A, Immohr L, Pein-Hackelbusch M Pharmaceutics. 2024; 16(5).

PMID: 38794320 PMC: 11125162. DOI: 10.3390/pharmaceutics16050658.

References

Yu L, Amidon G, Khan M, Hoag S, Polli J, Raju G . Understanding pharmaceutical quality by design. AAPS J. 2014; 16(4):771-83. PMC: 4070262. DOI: 10.1208/s12248-014-9598-3. View

Latha R, Lakshmi P . Electronic tongue: An analytical gustatory tool. J Adv Pharm Technol Res. 2012; 3(1):3-8. PMC: 3312724. DOI: 10.4103/2231-4040.93556. View

van Riet-Nales D, Kozarewicz P, Aylward B, de Vries R, Egberts T, Rademaker C . Paediatric Drug Development and Formulation Design-a European Perspective. AAPS PharmSciTech. 2016; 18(2):241-249. DOI: 10.1208/s12249-016-0558-3. View

Comoglu T, Ozyilmaz E . Orally disintegrating tablets and orally disintegrating mini tablets - novel dosage forms for pediatric use. Pharm Dev Technol. 2019; 24(7):902-914. DOI: 10.1080/10837450.2019.1615090. View

Panraksa P, Zhang B, Rachtanapun P, Jantanasakulwong K, Qi S, Jantrawut P . 'Tablet-in-Syringe': A Novel Dosing Mechanism for Dysphagic Patients Containing Fast-Disintegrating Tablets Fabricated Using Semisolid Extrusion 3D Printing. Pharmaceutics. 2022; 14(2). PMC: 8879151. DOI: 10.3390/pharmaceutics14020443. View

Cui M, Li Y, Wang S, Chai Y, Lou J, Chen F . Exploration and Preparation of a Dose-Flexible Regulation System for Levetiracetam Tablets via Novel Semi-Solid Extrusion Three-Dimensional Printing. J Pharm Sci. 2018; 108(2):977-986. DOI: 10.1016/j.xphs.2018.10.001. View

El-Say K, Ahmed T, Abdelbary M, Ali B, Aljaeid B, Zidan A . Risperidone oral disintegrating mini-tablets: A robust-product for pediatrics. Acta Pharm. 2015; 65(4):365-82. DOI: 10.1515/acph-2015-0038. View

Abdelhakim H, Coupe A, Tuleu C, Edirisinghe M, Craig D . Utilising Co-Axial Electrospinning as a Taste-Masking Technology for Paediatric Drug Delivery. Pharmaceutics. 2021; 13(10). PMC: 8540992. DOI: 10.3390/pharmaceutics13101665. View

Tawfik E, Scarpa M, Abdelhakim H, Bukhary H, Craig D, Barker S . A Potential Alternative Orodispersible Formulation to Prednisolone Sodium Phosphate Orally Disintegrating Tablets. Pharmaceutics. 2021; 13(1). PMC: 7832848. DOI: 10.3390/pharmaceutics13010120. View

10.

Alzoubi T, Martin G, Barlow D, Royall P . Stability of α-lactose monohydrate: The discovery of dehydration triggered solid-state epimerization. Int J Pharm. 2021; 604:120715. DOI: 10.1016/j.ijpharm.2021.120715. View

11.

Xu C, Zou M, Wang Y, Liu Y, Yan J, Wu Y . Discriminatory dissolution method for quality control measurements of carbamazepine immediate release tablets based on in vitro--in vivo investigations. Drug Dev Ind Pharm. 2011; 38(6):679-88. DOI: 10.3109/03639045.2011.621433. View

12.

Seoane-Viano I, Januskaite P, Alvarez-Lorenzo C, Basit A, Goyanes A . Semi-solid extrusion 3D printing in drug delivery and biomedicine: Personalised solutions for healthcare challenges. J Control Release. 2021; 332:367-389. DOI: 10.1016/j.jconrel.2021.02.027. View

13.

Poller B, Strachan C, Broadbent R, Walker G . A minitablet formulation made from electrospun nanofibers. Eur J Pharm Biopharm. 2017; 114:213-220. DOI: 10.1016/j.ejpb.2017.01.022. View

14.

Abdelhakim H, Coupe A, Tuleu C, Edirisinghe M, Craig D . Electrospinning Optimization of Eudragit E PO with and without Chlorpheniramine Maleate Using a Design of Experiment Approach. Mol Pharm. 2019; 16(6):2557-2568. PMC: 6549214. DOI: 10.1021/acs.molpharmaceut.9b00159. View

15.

Stoltenberg I, Breitkreutz J . Orally disintegrating mini-tablets (ODMTs)--a novel solid oral dosage form for paediatric use. Eur J Pharm Biopharm. 2011; 78(3):462-9. DOI: 10.1016/j.ejpb.2011.02.005. View

16.

Djordjevic N, Jankovic S, Milovanovic J . Pharmacokinetics and Pharmacogenetics of Carbamazepine in Children. Eur J Drug Metab Pharmacokinet. 2017; 42(5):729-744. DOI: 10.1007/s13318-016-0397-3. View

17.

Kobayashi Y, Habara M, Ikezazki H, Chen R, Naito Y, Toko K . Advanced taste sensors based on artificial lipids with global selectivity to basic taste qualities and high correlation to sensory scores. Sensors (Basel). 2012; 10(4):3411-43. PMC: 3274227. DOI: 10.3390/s100403411. View

18.

Liu F, Ranmal S, Batchelor H, Orlu-Gul M, Ernest T, Thomas I . Patient-centred pharmaceutical design to improve acceptability of medicines: similarities and differences in paediatric and geriatric populations. Drugs. 2014; 74(16):1871-1889. PMC: 4210646. DOI: 10.1007/s40265-014-0297-2. View

19.

Thabet Y, Klingmann V, Breitkreutz J . Drug Formulations: Standards and Novel Strategies for Drug Administration in Pediatrics. J Clin Pharmacol. 2018; 58 Suppl 10:S26-S35. DOI: 10.1002/jcph.1138. View

20.

Diaz-Torres E, Rodriguez-Pombo L, Ong J, Basit A, Santovena-Estevez A, Farina J . Integrating pressure sensor control into semi-solid extrusion 3D printing to optimize medicine manufacturing. Int J Pharm X. 2022; 4:100133. PMC: 9589180. DOI: 10.1016/j.ijpx.2022.100133. View