Mechanochemical Synthesis of Carvedilol Cocrystals Utilizing Hot Melt Extrusion Technology

Gasper J. Fernandes, Mahalaxmi Rathnanand, Vijay Kulkarni

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Purpose: To improve the solubility of carvedilol by preparing cocrystals utilizing solvent-free, continuous technology hot melt extrusion. Methods: Cocrystals of carvedilol and nicotinamide were formed in 1:2 ratio using hot melt extrusion (HME) by altering the parameters associated with the temperature of barrels and screw speed of the shaft. The product was characterized by DSC, PXRD, and FTIR, while the morphology was determined by SEM. Saturation solubility studies and dissolution rate were compared with carvedilol. Results: The processing parameters in HME significantly affected the cocrystallization which improved on changing the temperature and screw speed (cocrystals were formed when the temperature was set above the eutectic melting point). The obtained carvedilol cocrystals showed a distinct difference in morphological characteristics as compared to pure drug. The cocrystals showed the presence of additional peaks in DSC thermograph as well as band shifts in infrared spectrum. The powder XRD of cocrystals showed the difference in the 2θ values as compared with carvedilol indicating an interaction between carvedilol and nicotinamide. The saturation solubility studies and in vitro dissolution studies showed of cocrystals showed an increase in solubility and drug release, respectively, in 0.1N HCl. Conclusion: Hence, cocrystallization utilizing HME marks an important advantage over other conventional techniques. A single step, continuous process, scalable, and solvent-free HME process proved to be the best method to produce cocrystals on a larger scale with maximum yield. However, to further decrease the number of manufacturing steps, efforts are being made to combine crystallization and formulation in a single step.

Original languageEnglish
JournalJournal of Pharmaceutical Innovation
DOIs
Publication statusAccepted/In press - 01-01-2018

Fingerprint

Technology
Solubility
Niacinamide
Temperature
Fourier Transform Infrared Spectroscopy
Crystallization
Powders
Freezing
carvedilol
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science
  • Drug Discovery

Cite this

@article{50c9af58a57c4c08992dbe51a6f46cdc,
title = "Mechanochemical Synthesis of Carvedilol Cocrystals Utilizing Hot Melt Extrusion Technology",
abstract = "Purpose: To improve the solubility of carvedilol by preparing cocrystals utilizing solvent-free, continuous technology hot melt extrusion. Methods: Cocrystals of carvedilol and nicotinamide were formed in 1:2 ratio using hot melt extrusion (HME) by altering the parameters associated with the temperature of barrels and screw speed of the shaft. The product was characterized by DSC, PXRD, and FTIR, while the morphology was determined by SEM. Saturation solubility studies and dissolution rate were compared with carvedilol. Results: The processing parameters in HME significantly affected the cocrystallization which improved on changing the temperature and screw speed (cocrystals were formed when the temperature was set above the eutectic melting point). The obtained carvedilol cocrystals showed a distinct difference in morphological characteristics as compared to pure drug. The cocrystals showed the presence of additional peaks in DSC thermograph as well as band shifts in infrared spectrum. The powder XRD of cocrystals showed the difference in the 2θ values as compared with carvedilol indicating an interaction between carvedilol and nicotinamide. The saturation solubility studies and in vitro dissolution studies showed of cocrystals showed an increase in solubility and drug release, respectively, in 0.1N HCl. Conclusion: Hence, cocrystallization utilizing HME marks an important advantage over other conventional techniques. A single step, continuous process, scalable, and solvent-free HME process proved to be the best method to produce cocrystals on a larger scale with maximum yield. However, to further decrease the number of manufacturing steps, efforts are being made to combine crystallization and formulation in a single step.",
author = "Fernandes, {Gasper J.} and Mahalaxmi Rathnanand and Vijay Kulkarni",
year = "2018",
month = "1",
day = "1",
doi = "10.1007/s12247-018-9360-y",
language = "English",
journal = "Journal of Pharmaceutical Innovation",
issn = "1872-5120",
publisher = "Springer New York",

}

Mechanochemical Synthesis of Carvedilol Cocrystals Utilizing Hot Melt Extrusion Technology. / Fernandes, Gasper J.; Rathnanand, Mahalaxmi; Kulkarni, Vijay.

In: Journal of Pharmaceutical Innovation, 01.01.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mechanochemical Synthesis of Carvedilol Cocrystals Utilizing Hot Melt Extrusion Technology

AU - Fernandes, Gasper J.

AU - Rathnanand, Mahalaxmi

AU - Kulkarni, Vijay

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Purpose: To improve the solubility of carvedilol by preparing cocrystals utilizing solvent-free, continuous technology hot melt extrusion. Methods: Cocrystals of carvedilol and nicotinamide were formed in 1:2 ratio using hot melt extrusion (HME) by altering the parameters associated with the temperature of barrels and screw speed of the shaft. The product was characterized by DSC, PXRD, and FTIR, while the morphology was determined by SEM. Saturation solubility studies and dissolution rate were compared with carvedilol. Results: The processing parameters in HME significantly affected the cocrystallization which improved on changing the temperature and screw speed (cocrystals were formed when the temperature was set above the eutectic melting point). The obtained carvedilol cocrystals showed a distinct difference in morphological characteristics as compared to pure drug. The cocrystals showed the presence of additional peaks in DSC thermograph as well as band shifts in infrared spectrum. The powder XRD of cocrystals showed the difference in the 2θ values as compared with carvedilol indicating an interaction between carvedilol and nicotinamide. The saturation solubility studies and in vitro dissolution studies showed of cocrystals showed an increase in solubility and drug release, respectively, in 0.1N HCl. Conclusion: Hence, cocrystallization utilizing HME marks an important advantage over other conventional techniques. A single step, continuous process, scalable, and solvent-free HME process proved to be the best method to produce cocrystals on a larger scale with maximum yield. However, to further decrease the number of manufacturing steps, efforts are being made to combine crystallization and formulation in a single step.

AB - Purpose: To improve the solubility of carvedilol by preparing cocrystals utilizing solvent-free, continuous technology hot melt extrusion. Methods: Cocrystals of carvedilol and nicotinamide were formed in 1:2 ratio using hot melt extrusion (HME) by altering the parameters associated with the temperature of barrels and screw speed of the shaft. The product was characterized by DSC, PXRD, and FTIR, while the morphology was determined by SEM. Saturation solubility studies and dissolution rate were compared with carvedilol. Results: The processing parameters in HME significantly affected the cocrystallization which improved on changing the temperature and screw speed (cocrystals were formed when the temperature was set above the eutectic melting point). The obtained carvedilol cocrystals showed a distinct difference in morphological characteristics as compared to pure drug. The cocrystals showed the presence of additional peaks in DSC thermograph as well as band shifts in infrared spectrum. The powder XRD of cocrystals showed the difference in the 2θ values as compared with carvedilol indicating an interaction between carvedilol and nicotinamide. The saturation solubility studies and in vitro dissolution studies showed of cocrystals showed an increase in solubility and drug release, respectively, in 0.1N HCl. Conclusion: Hence, cocrystallization utilizing HME marks an important advantage over other conventional techniques. A single step, continuous process, scalable, and solvent-free HME process proved to be the best method to produce cocrystals on a larger scale with maximum yield. However, to further decrease the number of manufacturing steps, efforts are being made to combine crystallization and formulation in a single step.

UR - http://www.scopus.com/inward/record.url?scp=85056168184&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056168184&partnerID=8YFLogxK

U2 - 10.1007/s12247-018-9360-y

DO - 10.1007/s12247-018-9360-y

M3 - Article

AN - SCOPUS:85056168184

JO - Journal of Pharmaceutical Innovation

JF - Journal of Pharmaceutical Innovation

SN - 1872-5120

ER -