Continuous Manufacture and Scale-Up of Theophylline-Nicotinamide Cocrystals

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2021 Apr 3

PMID 33804705

Citations 1

Authors

Steven A Ross

Andrew P Hurt

Milan Antonijevic

Nicolaos Bouropoulos

Adam Ward

Pat Basford

Mark McAllister

Dennis Douroumis

Affiliations

Soon will be listed here.

Abstract

The aim of the study was the manufacturing and scale-up of theophylline-nicotinamide (THL-NIC) pharmaceutical cocrystals processed by hot-melt extrusion (HME). The barrel temperature profile, feed rate and screw speed were found to be the critical processing parameters with a residence time of approximately 47 s for the scaled-up batches. Physicochemical characterization using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction of bulk and extruded materials revealed the formation of high purity cocrystals (98.6%). The quality of THL-NIC remained unchanged under accelerated stability conditions.

Citing Articles

Creation of Hydrochlorothiazide Pharmaceutical Cocrystals Via Hot-Melt Extrusion for Enhanced Solubility and Permeability.

Narala S, Nyavanandi D, Alzahrani A, Bandari S, Zhang F, Repka M AAPS PharmSciTech. 2022; 23(1):56.

PMID: 35043282 DOI: 10.1208/s12249-021-02202-8.

References

Tiwari R, Patil H, Repka M . Contribution of hot-melt extrusion technology to advance drug delivery in the 21st century. Expert Opin Drug Deliv. 2016; 13(3):451-64. DOI: 10.1517/17425247.2016.1126246. View

Gordon S, Naelapaa K, Rantanen J, Selen A, Mullertz A, Ostergaard J . Real-time dissolution behavior of furosemide in biorelevant media as determined by UV imaging. Pharm Dev Technol. 2012; 18(6):1407-16. DOI: 10.3109/10837450.2012.737808. View

Malamatari M, Ross S, Douroumis D, Velaga S . Experimental cocrystal screening and solution based scale-up cocrystallization methods. Adv Drug Deliv Rev. 2017; 117:162-177. DOI: 10.1016/j.addr.2017.08.006. View

Butreddy A, Sarabu S, Bandari S, Dumpa N, Zhang F, Repka M . Polymer-Assisted Aripiprazole-Adipic Acid Cocrystals Produced by Hot Melt Extrusion Techniques. Cryst Growth Des. 2021; 20(7):4335-4345. PMC: 8081332. DOI: 10.1021/acs.cgd.0c00020. View

Khamar D, Pritchard R, Bradshaw I, Hutcheon G, Seton L . Polymorphs of anhydrous theophylline: stable form IV consists of dimer pairs and metastable form I consists of hydrogen-bonded chains. Acta Crystallogr C. 2011; 67(Pt 12):o496-9. DOI: 10.1107/S010827011104786X. View

Ward A, Brown B, Walton K, Timmins P, Conway B, Asare-Addo K . Application of Focus Variation Microscopy and Dissolution Imaging in Understanding the Behaviour of Hydrophilic Matrices. Pharmaceutics. 2020; 12(12). PMC: 7759878. DOI: 10.3390/pharmaceutics12121162. View

Ervasti T, Aaltonen J, Ketolainen J . Theophylline-nicotinamide cocrystal formation in physical mixture during storage. Int J Pharm. 2015; 486(1-2):121-30. DOI: 10.1016/j.ijpharm.2015.03.012. View

Bruni G, Maggi L, Mustarelli P, Sakaj M, Friuli V, Ferrara C . Enhancing the Pharmaceutical Behavior of Nateglinide by Cocrystallization: Physicochemical Assessment of Cocrystal Formation and Informed Use of Differential Scanning Calorimetry for Its Quantitative Characterization. J Pharm Sci. 2018; 108(4):1529-1539. DOI: 10.1016/j.xphs.2018.11.033. View

Narala S, Nyavanandi D, Srinivasan P, Mandati P, Bandari S, Repka M . Pharmaceutical Co-Crystals, Salts, and Co-Amorphous Systems: A Novel Opportunity of Hot Melt Extrusion. J Drug Deliv Sci Technol. 2021; 61. PMC: 7946067. DOI: 10.1016/j.jddst.2020.102209. View

10.

Reitz E, Podhaisky H, Ely D, Thommes M . Residence time modeling of hot melt extrusion processes. Eur J Pharm Biopharm. 2013; 85(3 Pt B):1200-5. DOI: 10.1016/j.ejpb.2013.07.019. View

11.

Berry D, Steed J . Pharmaceutical cocrystals, salts and multicomponent systems; intermolecular interactions and property based design. Adv Drug Deliv Rev. 2017; 117:3-24. DOI: 10.1016/j.addr.2017.03.003. View

12.

Bolla G, Nangia A . Multicomponent ternary cocrystals of the sulfonamide group with pyridine-amides and lactams. Chem Commun (Camb). 2015; 51(85):15578-81. DOI: 10.1039/c5cc06475a. View

13.

Arora K, Thakral S, Suryanarayanan R . Instability in theophylline and carbamazepine hydrate tablets: cocrystal formation due to release of lattice water. Pharm Res. 2013; 30(7):1779-89. DOI: 10.1007/s11095-013-1022-7. View

14.

Aher S, Dhumal R, Mahadik K, Ketolainen J, Paradkar A . Effect of cocrystallization techniques on compressional properties of caffeine/oxalic acid 2:1 cocrystal. Pharm Dev Technol. 2011; 18(1):55-60. DOI: 10.3109/10837450.2011.618950. View

15.

Eddleston M, Thakuria R, Aldous B, Jones W . An investigation of the causes of cocrystal dissociation at high humidity. J Pharm Sci. 2014; 103(9):2859-2864. DOI: 10.1002/jps.23865. View

16.

Kuminek G, Rodriguez-Hornedo N, Siedler S, Rocha H, Cuffini S, Cardoso S . How cocrystals of weakly basic drugs and acidic coformers might modulate solubility and stability. Chem Commun (Camb). 2016; 52(34):5832-5. PMC: 4893792. DOI: 10.1039/c6cc00898d. View

17.

Shevchenko A, Bimbo L, Miroshnyk I, Haarala J, Jelinkova K, Syrjanen K . A new cocrystal and salts of itraconazole: comparison of solid-state properties, stability and dissolution behavior. Int J Pharm. 2012; 436(1-2):403-9. DOI: 10.1016/j.ijpharm.2012.06.045. View

18.

Lima A, Pinho L, Chaker J, Sa-Barreto L, Marreto R, Gratieri T . Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products. Pharmaceutics. 2020; 12(8). PMC: 7464369. DOI: 10.3390/pharmaceutics12080779. View

19.

Padrela L, de Azevedo E, Velaga S . Powder X-ray diffraction method for the quantification of cocrystals in the crystallization mixture. Drug Dev Ind Pharm. 2011; 38(8):923-9. DOI: 10.3109/03639045.2011.633263. View

20.

Dhumal R, Kelly A, York P, Coates P, Paradkar A . Cocrystalization and simultaneous agglomeration using hot melt extrusion. Pharm Res. 2010; 27(12):2725-33. DOI: 10.1007/s11095-010-0273-9. View