Reliability evaluation of the design space of the granulation process of mefenamic acid tablets using a bootstrap resampling technique.

The design space of the granulation process of mefenamic acid tablets, based on Box and Behnken design datasets, was described by a response surface method incorporating multivariate spline interpolation. The reliability of the optimal solutions and the acceptance ranges were evaluated by a bootstrap (BS) resampling technique. The distribution of the BS optimal solutions was almost symmetrical; however, several solutions, which were quite different from the original solution, were mixed.

Effect of an experimental design for evaluating the nonlinear optimal formulation of theophylline tablets using a bootstrap resampling technique.

The optimal solutions of theophylline tablet formulations based on datasets from 4 experimental designs (Box and Behnken design, central composite design, D-optimal design, and full factorial design) were calculated by the response surface method incorporating multivariate spline interpolation (RSM(S)). Reliability of these solutions was evaluated by a bootstrap (BS) resampling technique. The optimal solutions derived from the Box and Behnken design, D-optimal design, and full factorial design dataset were similar.

Prediction of the aqueous solvation free energy of organic compounds by using autocorrelation of molecular electrostatic potential surface properties combined with response surface analysis.

Several quantitative structure-property relationship (QSPR) approaches have been explored for the prediction of aqueous solubility or aqueous solvation free energies, DeltaG(sol), as crucial parameter affecting the pharmacokinetic profile and toxicity of chemical compounds. It is mostly accepted that aqueous solvation free energies can be expressed quantitatively in terms of properties of the molecular surface electrostatic potentials of the solutes. In the present study we have introduced autocorrelation molecular electrostatic potential (autoMEP) vectors in combination with nonlinear response surface analysis (RSA) as alternative 3D-QSPR strategy to evaluate the aqueous solvation free energy of organic compounds.

Linear and nonlinear 3D-QSAR approaches in tandem with ligand-based homology modeling as a computational strategy to depict the pyrazolo-triazolo-pyrimidine antagonists binding site of the human adenosine A2A receptor.

The integration of ligand- and structure-based strategies might sensitively increase the success of drug discovery process. We have recently described the application of Molecular Electrostatic Potential autocorrelated vectors (autoMEPs) in generating both linear (Partial Least-Square, PLS) and nonlinear (Response Surface Analysis, RSA) 3D-QSAR models to quantitatively predict the binding affinity of human adenosine A3 receptor antagonists. Moreover, we have also reported a novel GPCR modeling approach, called Ligand-Based Homology Modeling (LBHM), as a tool to simulate the conformational changes of the receptor induced by ligand binding.

Evaluation of the reliability of nonlinear optimal solutions in pharmaceuticals using a bootstrap resampling technique in combination with Kohonen's self-organizing maps.

The response surface method incorporating multivariate spline interpolation (RSM-S) is a powerful technique for the formulation optimization of pharmaceuticals. However, no satisfactory method has been developed to evaluate the reliability of the optimal solution. We integrated bootstrap (BS) resampling and Kohonen's self-organizing maps (SOM) into RSM-S using the formulation optimization of theophylline tablets as the model experiment.

Bootstrap re-sampling technique to evaluate the optimal formulation of theophylline tablets predicted by non-linear response surface method incorporating multivariate spline interpolation.

Optimal solutions of theophylline tablet formulations were derived from three types of experimental datasets, composed of different numbers of data-points using the response surface method incorporating multivariate spline interpolation (RSM(S)). The reliability of these optimal solutions was evaluated by a bootstrap re-sampling technique. Different levels of three causal factors were used as factors of response surface analysis: the lactose/cornstarch ratio (X(1)), the amount of carmellose calcium (X(2)), and the amount of hydroxypropylcellulose (X(3)).

Application of QSAR analysis to organic anion transporting polypeptide 1a5 (Oatp1a5) substrates.

Organic anion transporting polypeptide 1a5, Slco1a5 (previously called Oatp3, Slc21a7) is a multispecific transmembrane transport protein that belongs to the OATP/SLCO superfamily of solute carriers. It is expressed in several epithelial barriers such as the small intestine and the choroid plexus where it might play an important role in the disposition of numerous endogenous and exogenous organic compounds. Since the molecular basis of the multispecificity of Oatp1a5 is not known and the three-dimensional structure not solved yet, we used three-dimensional quantitative structure-activity relationship (3D-QSAR) techniques to obtain topological information on the substrate binding site of the protein.