Pharmaceutical Co-crystal technique

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CO-CRYSTAL TECHNIQUE

PRESENTED BY MANOJ KUMAR AMITY UNIVERSITY


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.


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.


• 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.


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.


TYPE OF SOLID FORM


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.


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.


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


• Grinding method

• Slurry Conversion method Solvent

Crystal

Stirring at R.T.

Decantation Drying PXRD


SUPERCRITICAL FLUID TECHNOLOGY


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


EVALUATION METHODS

• PXRD (Powder X-rays diffraction study)

• IR- Spectroscopic

• Scanning Electron Microscope

• Percentage Yield


• Determination Of Melting Point

• Solubility Analysis

• Compatibility Studies (IR Spectroscopy)

• In vitro drug release studies-


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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Pharmaceutical Co-crystal technique

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