1. CO-CRYSTAL TECHNIQUE
PRESENTED BY
MANOJ KUMAR
AMITY
UNIVERSITY
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2. 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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3. 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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4. • 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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5. 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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6. TYPE OF SOLID FORM
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7. 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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8. 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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9. METHODS OF CO-CRYSTAL
PREPARATION1-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 TECHNOLOGY
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10. • Grinding method
• Slurry Conversion method
Solvent
Crystal
Stirring at R.T.
Decantation
Drying
PXRD
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11. SUPERCRITICAL FLUID TECHNOLOGY
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12. 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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14. EVALUATION METHODS
• PXRD (Powder X-rays diffraction study)
• IR- Spectroscopic
• Scanning Electron Microscope
• Percentage Yield
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15. • Determination Of Melting Point
• Solubility Analysis
• Compatibility Studies (IR Spectroscopy)
• In vitro drug release studies-
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16. 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
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• Co-crystals of indomethacin
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