CO-CRYSTAL TECHNIQUE

PRESENTED BY
MANOJ KUMAR
AMITY

UNIVERSITY
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 INTRODUCTION

• Out of the 40% or more NCEs being generated,

nearly 60% of them are poorly water soluble.

• These poorly water soluble drugs having slow drug

absorption leads to inadequate and variable
bioavailability and gastrointestinal mucosal toxicity.

• Therefore, enhancing the aqueous solubility of poorly

water soluble drugs is a major challenge for the
pharmaceutical researchers.

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 PHARMACEUTICAL CO-CRYSTAL
• Pharmaceutical co-crystals can be defined as crystalline
materials comprised of an API and one or more unique
co-crystal formers, which are solids at room
temperature.

• Co-crystals can be constructed through several types

of interaction, including hydrogen bonding, π-stacking,
and Van der Waals forces.

• The first known co-crystal Quinhydrone, was studied

by Friedrich Wöhler in 1844.

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• Co-crystals can be divided into:
1- Co-crystal anhydrates
2-Co-crystal hydrates (solvates)
3-Anhydrates of co-crystals of salts
4-Hydrates (solvates) of co-crystals of salts.

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 ADVANTAGES OF CO-CRYSTAL

1- It is a stable crystalline form as compared to amorphous

solid.
2- It can enhance the solubility of poorly water soluble
drugs.
3- It can also enhance the bioavailability due to increased
solubility.
4- Co-crystal formation technique may be used for
purification steps.

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TYPE OF SOLID FORM

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 CO-FORMERS-
• Co-formers are the most important components of the
co-crystal.
• The co-crystal formation is based on the structure of the
co-formers.
• The solubility of co-crystal is also depends on the
solubility of the co-formers.
• Some examples like ascorbic acid, gallic acid,
nicotinamide, citric acid , aglutamic acid, histidine,
urea, saccharine, glycine,tyrosine,valine.

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 SOLVENTS-
• Solvents are also important ingredients of co-crystal
formation.
• The co-crystal formation is also depend on the selection
of solvents.
• Selection of solvents depend on the solubility of drug
and co-formers.
• Some example of solvents used in co-crystal formation
like-ethanol, methanol, acetonitrile and others organic
solvents.

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 METHODS OF CO-CRYSTAL
PREPARATION-
1-SOLUTION METHODS-
• Evaporative co-crystallization
• Cooling crystallization
• Reaction crystallization
2-GRINDING METHOD
• Neat/Dry grinding method
• Liquid assisted grinding method
3-ANTISOLVENT METHOD
4-SLURRY CONVERSION METHOD
5-SUPERCRITICAL FLUID
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• Grinding method

• Slurry Conversion method

Solvent

Crystal

Stirring at R.T.

Decantation Drying PXRD

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SUPERCRITICAL FLUID TECHNOLOGY

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STEPS INVOLVED IN FORMATION OF
CO-CRYSTAL-
• Selection of API
• Selection of co-former
• Empirical and theoretical guidance
• Co-crystal screening
• Co-crystal characterization
• Co-crystal performation

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 EVALUATION METHODS

• PXRD (Powder X-rays diffraction study)

• IR- Spectroscopic

• Scanning Electron Microscope

• Percentage Yield

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• Determination Of Melting Point

• Solubility Analysis

• Compatibility Studies (IR Spectroscopy)

• In vitro drug release studies-

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 MARKETED PREPARATION-
• Pharmaceutical co-crystals of carbamazepine
(Tegretol® )
• Pharmaceutical co-crystals of fluoxetine
hydrochloride (Prozac® )
• Pharmaceutical co-crystals of itraconazole
(Sporanox® )
• Pharmaceutical co-crystals of sildenafil (Viagra® )
• Co-crystal of melamine and cyanuric acid
• Co-crystals of theophylline
• Co-crystals of aceclofenac
• Co-crystal of 5-nitrouracil
• Co-crystals of indomethacin
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