pharmaceutical co-crystal technique
DESCRIPTION
TRANSCRIPT
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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 TECHNOLOGY
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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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