A crystal engineering design to enhance the solubility, dissolution, stability and micrometric properties of omeprazole via Co-crystallization techniques

Abstract

Introduction: Omeprazole, a proton-pump inhibitor used in peptic ulcers, gastro-oesophageal-reflux disorder, Zollinger-Ellison syndrome and in H.pylori infections. The omeprazole is unstable at acidic pH, undergoes degradation in stomach. To prevent the degradation in stomach, dosage forms are supplied as enteric-coated tablets or granules encapsulated in gelatin capsules. The efficiency of such dosage forms depends upon the extent of coating, solubility of coating material, type of dosage forms; in addition this it is insoluble in water, having poor bioavailability. To overcome these major drawbacks of omeprazole, an novel technique: co-crystallization was attempted, to produce a stable, enhancement in solubility and improved micromeritic properties of omeprazole. Co-crystals consists of API and a stoichiometric amount of a pharmaceutically acceptable co-crystal former. Pharmaceutical Co-crystals are non-ionic supramolecular complexes and can be used to address physical property issues such as solubility, stability and bioavailability in pharmaceutical development without changing the chemical composition of the API. Co-crystal is a crystalline entity formed by two different or more molecular entities where the intermolecular interactions are weak forces like hydrogen bonding and π-π stacking. Materials and methods: As omeprazole is unstable in acidic pH, very hygroscopic character, photosensitive and thermolebility in nature, Anti solvent addition method was used for preparation of crystals. Poly Vinyl Pyrrolidone is taken as co-former, magnesium chloride and sodium bicarbonate as basic substances. Further prepared crystals were characterized by Powder X-ray Diffractometer (PXRD), Differential scanning colorimeter (DSC), Fourier Transformation Infra-red Spectroscopy (FTIR).Moreover they were studied for melting point determination, flow property studies (micromeritic properties), dissolution studies, solubility test and stability tests. Results and discussion: FTIR revealed that there is no formation of hydrogen bonding between drug and co-former; hence it states that co-crystals are not formed, but XRD and DSC states that there is a formation of some physical interaction, partial crystalline and amorphous form which is a new crystal lattice. Conclusion: Formed crystals produce moderate improvement in micromeritic properties, solubility, stability and dissolution behaviour of drug. Thus physicochemical properties of omeprazole were improved via crystal engineering technique-co-crystallization.