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  • Title: Solid state manipulation of lornoxicam for cocrystals--physicochemical characterization.
    Author: Nijhawan M, Santhosh A, Babu PR, Subrahmanyam CV.
    Journal: Drug Dev Ind Pharm; 2014 Sep; 40(9):1163-72. PubMed ID: 23829186.
    Abstract:
    CONTEXT: Lornoxicam is an analgesic and anti-inflammatory drug of choice and belongs to Class II (low solubility) of BCS (Biopharmaceutical Classification System). Thus bioavailabilities problems are predominant. OBJECTIVE: Through crystal engineering approach, a method was developed for obtaining multi-component cocrystals of lornoxicam using pharmaceutically acceptable compounds as guests. MATERIALS AND METHODS: Lornoxicam guest-free form was obtained from solution crystallization. Supramolecular synthon approach indicated that lornoxicam was in orthorhombic form. Further presence of intermolecular hydrogen bonding with layered structures was identified. Solvent drop grinding method permitted the formation of cocrystals of lornoxicam with catechol, resorcinol, benzoic acid, hydroxyquinone and 2,4 dihydroxy benzoic acid, all are capable of forming hydrogen bonding. RESULTS AND DISCUSSION: Lornoxicam cocrystals exhibited the difference in melting points and decomposition characteristics. The analysis of infrared (IR) indicated the shifting of characteristic bands of lornoxicam. The XPRD (X-Ray Powder Diffraction) pattern indicated the crystallinity of cocrystals and significant difference in 2θ value of intense peaks. Differential scanning calorimetry spectra of cocrystals denoted the changes in fusion endotherms, which are in agreements with melting points. The pH solubility profile of lornoxicam showed sigmoidal curve, which substantiated the pKa-dependent solubility. Lornoxicam cocrystals also exhibited a similar pH-solubility profile. Thus pairing of lornoxicam and coformers in the solution at high pH media was assumed. The in vitro dissolution studies of cocrystals were conducted at pH 4.0. The rapid rate of dissolution of cocrystals was observed in initial 10 min. The extent of dissolution was enhanced by 20% on account of cocrystallization. CONCLUSION: The lornoxicam cocrystals were obtained with improved physicochemical characteristics.
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