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AAPS PharmSciTech

, 20:28 | Cite as

In Situ Cocrystallization of Dapsone and Caffeine during Fluidized Bed Granulation Processing

  • Valerio TodaroEmail author
  • Zelalem Ayenew Worku
  • Lucio Mendes Cabral
  • Anne Marie Healy
Research Article

Abstract

Different pharmaceutical manufacturing processes have been demonstrated to represent feasible platforms for the production of pharmaceutical cocrystals. However, new methods are needed for the manufacture of cocrystals on a large scale. In this work, the suitability of the use of a fluidized bed system for granulation and concomitant cocrystallization was investigated. Dapsone (DAP) and caffeine (CAF) have been shown to form a stable cocrystal by simple solvent evaporation. DAP is the active pharmaceutical ingredient (API) and CAF is the coformer. In the present study, DAP-CAF cocrystals were produced through liquid-assisted milling and the product obtained was used as a cocrystal reference. The granulation of DAP and CAF was carried out using four different experimental conditions. The solid-state properties of the constituents of the granules were characterised by differential scanning calorimetry (DSC) and x-ray powder diffraction (PXRD) analysis while the granule size distribution and morphology were investigated using laser diffraction and scanning electron microscopy (SEM), respectively. DAP-CAF cocrystal granules were successfully produced during fluidized bed granulation. The formation of cocrystals was possible only when the DAP and CAF were dissolved in the liquid phase and sprayed over the fluidized solid particles. Furthermore, the presence of polymers in solution interferes with the cocrystallization, resulting in the amorphization of the DAP and CAF. Cocrystallization via fluidized bed granulation represents a useful tool and a feasible alternative technique for the large scale manufacture of pharmaceutical cocrystals for solid dosage forms.

KEY WORDS

cocrystals fluidized bed granulation ball milling pharmaceutical processing 

Abbreviations

DAP

Dapsone

CAF

Caffeine

API

Active pharmaceutical ingredient

DSC

Differential scanning calorimetry

PXRD

Powder x-ray diffraction

SEM

Scanning electron microscopy

BCS

Biopharmaceutics Classification System

FBG

Fluidized bed granulation

MCC

Microcrystalline cellulose

PVP

Polyvinylpyrrolidone

HPMC

Hydroxypropyl methylcellulose

EXP

Experimental conditions

SI

Stability index

FRI

Flow rate index

AIF

Angle of internal friction

ffc

Flow function coefficient

CBD

Conditioned bulk density

Notes

Funding

This publication has emanated from research supported in part by a research grant from Science Foundation Ireland (SFI) and is co-funded under the European Regional Development Fund under Grant Number 12/RC/2275.

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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Valerio Todaro
    • 1
    Email author
  • Zelalem Ayenew Worku
    • 1
  • Lucio Mendes Cabral
    • 2
  • Anne Marie Healy
    • 1
  1. 1.Synthesis and Solid State Pharmaceutical Centre, School of Pharmacy and Pharmaceutical SciencesTrinity College DublinDublinIreland
  2. 2.Department of Drugs and Pharmaceutics, Faculty of PharmacyFederal University of Rio de JaneiroRio de JaneiroBrazil

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