The cognitive and behavioral symptoms of nonverbal learning disabilities (NLD) have been described by previous investigators. Nevertheless, we know far less about the potential genetic contributions that may predispose a child to have NLD. An endophenotype model was investigated in 5 samples of children ages 9 to 15 years: NLD (n = 32); reading disorders (RD; n = 59); participants with a psychiatric diagnosis but without a learning disability (n = 55); typically developing controls (n = 31); and children with velocardiofacial syndrome (VCFS), a chromosomal deletion syndrome that has been proposed as being an exemplar of NLD (VCFS + NLD; n = 20). Based on a family genetic interview, the authors' data suggest that children with NLD, RD, or a psychiatric diagnosis have a higher prevalence rate of attention-deficit/hyperactivity disorder (ADHD) and substance abuse/dependence. Psychiatric controls and children with NLD--but not children with RD-- showed higher prevalence rates of familial bipolar disorder.

Purpose: To enhance the solubility and dissolution profile of simvastatin (SIM) through cocrystallization with varying ratios of nicotinamide (NIC) using various co-methods. Materials and Methods: Twelve SIM:NIC co-crystal formulations (F01-F12) were prepared using dry grinding, slurry, liquid-assisted grinding, and solvent-evaporation methods, and their properties compared. Optimized formulations were selected on the basis of dissolution profiles and solubility for in vivo studies. The angle of repose, Carr Index and Hausner ratio were calculated to evaluate flow properties. Differential light scattering (DLS) was used to estimate particle-size distribution. Scanning electron microscopy (SEM) was employed to evaluate surface morphology. Thermal analyses and Fourier-transform infrared (FTIR) spectroscopy were used to determine the ranges of thermal stability and physical interaction of formulated co-crystals. X-ray powder diffraction (XPD) spectroscopy was used to determine the crystalline nature. Solubility and dissolution studies were undertaken to determine in vitro drug-release behaviors. Results: Micromeritic analyses revealed the good flow properties of formulated co-crystals. DLS showed the particle size of co-crystals to be in the nanometer range. SEM revealed that the co-crystals were regular cubes. Thermal studies showed the stability of co-crystals at >300°C. FTIR spectroscopy revealed minor shifts of various peaks. XPD spectroscopy demonstrated cocrystal formation. The formulations exhibited an improved dissolution profile with marked improvements in solubility. In vivo studies showed a 2.4-fold increase in C max whereas total AUC (0-∞) was increased 4.75-fold as compared with that of SIM tablets. Conclusion: Co-crystallization with NIC improved the solubility and dissolution profile and, hence, the bioavailability of the poorly water-soluble drug SIM.

The purpose of current study was to improve the solubility and dissolution profile of BCS class-II drug Glipizide using glutaric acid as a coformer via various cocrystallization techniques i.e., dry grinding, liquid-assisted grinding, slurry, and solvent evaporation. Fourier Transform Infrared Spectroscopy (FTIR) was performed to determine the interaction between components of glipizide-glutaric acid (GPZ-GLU) cocrystals. Powder X-ray Diffraction (PXRD) studies confirmed the crystalline nature of formulated cocrystals. Scanning Electron Microscopy (SEM) revealed cylindrical to rectangular shape of cocrystals. Flow properties of GPZ-GLU cocrystals were evaluated by micromeritics analysis. Size and surface morphology was determined by zeta sizer analysis and optical microscopy. Differential scanning calorimetry (DSC) and Thermogravimetric (TGA) analysis were performed to determine the melting points as well as thermal stability of pure components and formulated GPZ-GLU cocrystals. In vitro drug release studies were carried out using dissolution apparatus-II. GPZ-GLU cocrystals showed higher drug release at pH 6.8 as compared to pH 1.2. However, percent drug release of optimum formulations at pH 6.8 was determined as; 24-92.2% (F3) and 12.0-93.5% (F7). Solubility studies revealed improved solubility as compared to the pure drug in water i.e., 53 folds and 54.27 folds from F3 and F7 cocrystals, respectively. Finally, it was concluded that glutaric acid has improved the solubility and dissolution profile of glipizide. However, many cocrystal formers have been reported in the literature that can be used to enhance the physicochemical properties as well as the bioavailability of poorly soluble drugs via cocrystallization technique.

Purpose: To synthesize anticonvulsant drug derivatives that target protease-activated receptor generated epileptic seizures.Method: Varieties of carbamazepine-based Schiff bases were designed with different aldehydes and ketones, and evaluated for in silico computer-aided drug design prediction of absorption, distribution, metabolism and excretion (ADME), and potential drug targets. The resultant compounds were synthesized and characterized by various spectroscopic techniques, including FTIR, 1H-NMR and 13CNMR, analysis. Thereafter, they were screened for antimicrobial, antioxidant and anticonvulsant potential.Results: Prominent anti-protease potential was shown by C7 and C3 compounds and the order of activity was C7 > C3 > C5 > C2 > C6 > C4 > C2 > C1 (p < 0.05). The anticonvulsant activity of C7 and C5 was comparable with the standard drug; C3, C4, C6 and C8 had mild activity while C1 and C4 showed the least activity. The synthesized compounds exhibited significant (p < 0.05) antioxidant potential (rank order: C3 > C4 > C5 > C7 > C8 > C6 > C1 > C2) and antimicrobial activity against S.aureus and B. bronchiseptica (rank order: C5 > C2 > C8 > C1 > C4 > C3 > C7).Conclusion: Synthesized derivatives retained their potential for anticonvulsant and antitrypsin activity, unlike their mother moiety, i.e., carbamazepine. The additional antibacterial activity effectively treats neurological disorders associated with bacterial infections.

Purpose: To synthesize anticonvulsant drug derivatives that target protease-activated receptor generated epileptic seizures.Method: Varieties of carbamazepine-based Schiff bases were designed with different aldehydes and ketones, and evaluated for in silico computer-aided drug design prediction of absorption, distribution, metabolism and excretion (ADME), and potential drug targets. The resultant compounds were synthesized and characterized by various spectroscopic techniques, including FTIR, 1H-NMR and 13CNMR, analysis. Thereafter, they were screened for antimicrobial, antioxidant and anticonvulsant potential.Results: Prominent anti-protease potential was shown by C7 and C3 compounds and the order of activity was C7 > C3 > C5 > C2 > C6 > C4 > C2 > C1 (p < 0.05). The anticonvulsant activity of C7 and C5 was comparable with the standard drug; C3, C4, C6 and C8 had mild activity while C1 and C4 showed the least activity. The synthesized compounds exhibited significant (p < 0.05) antioxidant potential (rank order: C3 > C4 > C5 > C7 > C8 > C6 > C1 > C2) and antimicrobial activity against S.aureus and B. bronchiseptica (rank order: C5 > C2 > C8 > C1 > C4 > C3 > C7).Conclusion: Synthesized derivatives retained their potential for anticonvulsant and antitrypsin activity, unlike their mother moiety, i.e., carbamazepine. The additional antibacterial activity effectively treats neurological disorders associated with bacterial infections.