Fabrication and Optimization of Novel Lornoxicam Matrix Tablets Using 3-Factor 3-Level Box-Behnken Statistical Design: Invitro and Invivo Evaluation.

In the present study efforts have been made to prepare sustained release matrix tablets of Lornoxicam. Matrix tablets were prepared by direct compression method by using Hydroxypropyl methyl cellulose K15 (HPMC- K15), Ethyl cellulose (EC) and Sodium carboxy methyl cellulose (Na-CMC) as polymers in different concentrations. A 3-factor 3- level Box-Behnken statistical design was used as an optimization tool having total of 17 experimental runs with 5 central points. All three polymers were selected as independent variables while %age drug release at various time intervals and hardness were used as dependant variables. In vivo studies were conducted on human plasma using Tenoxicam as internal standered. All the detections were made on SYKNM HPLC. Foriour Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetery (DSC) studies were conducted and no chemical interaction was found between drug and polymers. The drug release mechanism was mainly governed by non-fickian (anomalous) diffusion and zero-order (case II) transport diffusion. Regression analysis was performed on dissolution data obtained with the selected response variables and polynomial models were constructed. Polynomial models were further validated using one way ANOVA and results indicated that all the polymers used have significant effect on selected response (p>0.05). Contour plots and three dimensional response surface curves were drawn. In- vivo studies were conducted on two tablet formulation indicating slow and sustained release of the drug from matrix. From Behnken design it is possible to successfully formulate and optimize Lornoxicam sustained release matrix tablets with three polymers (HPMC- K15, EC and Na-CMC) in combination.

Recognition of DNA-arginine photoadduct by anti-DNA autoantibodies in systemic lupus erythematosus.

BACKGROUND & OBJECTIVES: Studies have been carried out to synthesize and characterize the photoconjugate between positively charged amino acid, arginine and DNA fragments and their role in the induction of anti-DNA antibodies. METHODS: Calf thymus DNA fragments of about 200 base pairs (bp) were covalently crosslinked with arginine under UV light. The amino acid was found to be covalently photoconjugated to DNA and resulted in the formation of a crosslink. The photoadduct was characterized by various physicochemical methods. RESULTS: Photoaddition of arginine to 200 bp DNA rendered the nucleic acid conformer thermodynamically more stable than the native form. After systematic characterization of the photoadduct, it was used as an antigen for the generation of antibodies in experimental animals. The photoadducts were found to be immunogenic in rabbits, inducing high titre antibodies. The DNA-arginine photoadduct showed higher binding with SLE sera known to have high level of anti-DNA antibodies. INTERPRETATION & CONCLUSION: Naturally occurring anti-DNA autoantibodies were found to recognize DNA-arginine photoadduct. The recognition of DNA-arginine photoadduct by anti-DNA autoantibodies points to the role of modified DNA in the induction of anti-DNA antibodies in autoimmune disorders.