1. PHARMACEUTICAL CO-CRYSTAL TECHNIQUE
STUDENTNAME:- ABHISHEKBORKAR
CLASS- B- PHARM3RD YEAR
SHRADDHAINSTITUTEOF PHARMACYKONDALA ZAMBRE, WASHIM-444505

2. INTRODUCTION
• 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.

3. PHARMACEUTICAL CO-CRYSTAL
• 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.

4. ADVANTAGES OF COCRYSTAL
• 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.

5. TYPES

6. CO-FORMERS
• HE 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.

7. SOLVENTS
• 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.

8. METHOD OF CO-CRYSTAL PREPARATION SOLUTION METHODS
• EVAPORATIVE CO-CRYSTALLIZATION
• COOLING CRYSTALLIZATION
• GRINDING METHOD
• NEAT/DRY GRINDING METHOD
• LIQUID ASSISTED GRINDING METHOD
• ANTISOLVENT METHOD
• SLURRY CONVERSION METHOD
• SUPERCRITICAL FLUID TECHNOLOGY

9. STEPS INVOLVED IN PREPARATION
• SELECTION OF API
• SELECTION OF CO-FORMER
• EMPIRICAL AND THEORETICAL GUIDANCE
• CO-CRYSTAL SCREENING
• CO-CRYSTAL CHARACTERIZATION
• CO-CRYSTAL PERFORMANCE

10. • SYNTHON :PART /CONSTITUENT OF API AND COFORMER
INVOLVED IN INTERMOLECULAR INTERACTION
• SYNTHONS EXIST IN TWO DISTINCT CATEGORIES:
• SUPRAMOLECULAR HOMO- SYNTHONS THAT ARE
COMPOSED OF IDENTICAL COMPLEMENTARY FUNCTIONAL
GROUPS SUCH AS CARBOXYLIC ACID DIMERS (ASPIRIN)
• SUPRAMOLECULAR HETERO- SYNTHONS COMPOSED OF
DIFFERENT BUT COMPLEMENTARY FUNCTIONAL GROUPS
SUCH AS ACID–WEAKLY BASIC NITROGEN (ASPIRIN–
MELOXICAM) AND ACID–AMIDE (ASPIRIN–
CARBAMAZEPINE)

11. •EVALUATION METHODS
• PXRD (POWDER X-RAYS DIFFRACTION STUDY)
• IR- SPECTROSCOPIC
• SCANNING ELECTRON MICROSCOPE
• PERCENTAGE YIELD
• DETERMINATION OF MELTING POINT
• SOLUBILITYANALYSIS
• COMPATIBILITY STUDIES (IR SPECTROSCOPY)
• IN VITRO DRUG RELEASE STUDIES

12. •MARKETED FORMULATION
• 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

13. THANK YOU ….