Solid state investigations of selected drugs for physicochemical properties

Abstract

Cocrystal approach is used to modify the physicochemical properties of drugs, particularly hydrophobic drugs or Class II drugs of Biopharmaceutics Classification System (BCS). Cocrystals exhibit higher solubility, rapid dissolution and enhanced bioavailability than the crystalline drugs. Hence, cocrystals of a drug address the intellectual property issues by extending the life cycle of APIs. In this abstract, two poorly water-soluble drugs, namely lornoxicam and irbesartan, were reported for solid state investigation. Lornoxicam is used for anti-inflammatory and analgesic activities. Lornoxicam belongs to Class II of BCS and tmax is nearly 2.5 h. Rapid onset and increased extent of bioavailability are desirable for analgesics of this type. Hence, it is suitable drug for solid state manipulation. Lornoxicam single crystal was obtained from acetonitrile. It exhibited zwitter ionic state and formed orthorhombic crystal system. The lornoxicam molecules formed zigzag tapes. Lornoxicam is weakly basic (pKa is 4.7) and several GRAS approved acid coformers can be utilized for preparing cocrystals. Based on the approach of and#61508;pKa values (and#61508;pKa and#61603; 3), lornoxicam and 15 coformers were chosen to prepare cocrystals. Solvent assisted grinding was adopted. Characterization of cocrystals with melting points indicated the formation of five cocrystals. Lowering of melting points is observed. Coformers, such as catechol, resorcinol, hydroquinone, benzoic acid and 2.4 dihydroxy benzoic acid, were able to interact with lornoxicam, which facilitated the formation of cocrystals. FTIR studies showed significant changes in the O-H, N-H, and CO-NH band transitions in five lornoxicam cocrystals. The DSC exhibited changes in the characteristic endothermic melting transitions followed by decomposition by five cocrystals. Powder XRD pattern of lornoxicam cocrystals indicated the presence of additional peaks and shifting of pure drug peaks indicating crystallinity changes. Thus, formation of cocrystals was confirmed. newline