• 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 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
• 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
2- It can enhance the solubility of poorly water soluble
3- It can also enhance the bioavailability due to increased
4- Co-crystal formation technique may be used for
TYPE OF SOLID FORM
CO-FORMERS• Co-formers are the most important components of the
• The co-crystal formation is based on the structure of the
• 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
• The co-crystal formation is also depend on the selection
• Selection of solvents depend on the solubility of drug
• Some example of solvents used in co-crystal formation
like-ethanol, methanol, acetonitrile and others organic