Genome-Wide Supported Risk Variants in MIR137, CACNA1C, CSMD1, DRD2, and GRM3 Contribute to Schizophrenia Susceptibility in Pakistani Population

OBJECTIVE: Schizophrenia is a chronic neuropsychiatric disease afflicting around 1.1% of the population worldwide. Recently, MIR137, CACNA1C, CSMD1, DRD2, and GRM3 have been reported as the most robustly emerging candidates involved in the etiology of schizophrenia. In this case control study, we performed an association analysis of rs1625579 (MIR137), rs1006737, rs4765905 (CACNA1C), rs10503253 (CSMD1), rs1076560 (DRD2), rs12704290, rs6465084, and rs148754219 (GRM3) in Pakistani population. METHODS: Schizophrenia was diagnosed on the basis of the Diagnostic and Statistical Manual of Mental Disorders 4th ed (DSM-IV). Detailed clinical information, family history of all patients and healthy controls were collected. RFLP based case control association study was performed in a Pakistani cohort of 508 schizophrenia patients and 300 healthy control subjects. Alleles and genotype frequencies were calculated using SPSS. RESULTS: A significant difference in the genotype and allele frequencies for rs4765905, rs1076560 and rs6465084 were found between the patients and controls (p=0.000). CONCLUSION: This study provides substantial evidence supporting the role of CACNA1C, GRM3 and DRD2 as schizophrenia susceptibility genes in Pakistani population.

Formulation development and evaluation of diltiazem HCl sustained release matrix tablets using HPMC K4M and K100M

The aim of this study was to develop a sustained release hydrophilic matrix tablet of Diltiazem HCl and evaluates the effect of formulation variables [e.g. lubricant, binder, polymer content and viscosity grades of HPMC] on drug release. Twelve different formulations [F1-F12] were prepared by direct compression. The results of the physical parameters and assay were found to be within the acceptable range. Rate of drug release was found to be slow as the fraction of the polymer was increased from 20-50%. The drug release rate from tablets containing K4M was effectively controlled by increasing the talc concentration, whereas the burst effect was reduced by increasing binder content. The drug release was higher with K4M as compare to K100M. Model-dependent and independent methods were used for data analysis and the best results were observed for K4M in Higuchi [R[2]=0.9903-0.9962] and K100M in Baker and Lonsdale [R[2]=0.9779-0.9941]. The release mechanism of all formulations was non-Fickian. F7 [50% K4M, 2% talc, 10% Avicel PH101] and F11 [40% K100M] were very close to targeted release profile. F12 [50% K100M] exhibited highest degree of swelling and lowest erosion. The f[1] and f[2] test were performed taking F11 as a reference formulation