Prediction of permeability of FD-4 through porous poly (2-hydroxyethyl methacrylate) membrane by multiple linear regression and artificial neural network.

The aim of this study was to predict the permeability through porous poly (2-hydroxyethyl methacrylate) (pHEMA) membranes of fluorescein isothiocyanate-labeled dextran molecular weight 4400 (FD-4) as a model of peptide and protein drug movement. Homogeneous standard membranes were prepared by redox polymerization. Permeability data were predicted by an artificial neural network (ANN) as a function of polymerization factors, and the accuracy was compared with that of conventional multiple linear regression (MLR). Good linearity was observed with each model, with the correlation coefficient of a leave-one-out cross-validation (Rcross) being 0.857 for the MLR model and 0.876 for the ANN model. The mean bias and mean accuracy for the ANN were somewhat smaller than those of the MLR. The ANN method provides an accurate quantitative approximation of the permeability coefficient of FD-4, as judged by conventional MLR, and could be applied to prediction of the non-linear relation between polymerization factors and the permeability of FD-4.

Factors affecting release rate of diltiazem hydrochloride from poly (2-hydroxyethyl methacrylate) matrices.

Sustained release diltiazem hydrochloride (DIL) formulation is widely used over 110 countries worldwide, and is among the drugs recommended as a first-line therapy in the major guidelines for the management of hypertension. In search for a most suitable controlled release formulation of DIL, we investigated poly (2-hydroxyethyl methacrylate) matrix (pHEMA matrix) synthesized by photopolymerization. Factors affecting the release rate of DIL from pHEMA matrices were investigated, focusing on the internal structure of the matrices. The effects of the porosity (epsilon), the fractal dimensions (Df) and the microscopic viscosity (eta matrix) of the matrices on the release rate of DIL were investigated on the basis of the linear least square equation as well as the Higuchi's equation. A relation between the actual value and predicted value based on the linear least square equation exhibited a fairly good linearity (r=0.979). Furthermore, the release rate of DIL was represented based on the Higuchi's equation including the values of epsilon, Df and eta matrix. It is likely that the release rate of DIL from pHEMA matrices is mainly controlled by epsilon and Df, but eta matrix was less effective.

[The reduction in the local anesthetic dose required for a caudal epidural block in infants and children using a Teflon cannula].

We investigated the spread of mepivacaine mixed with a radio-opaque substance in caudal epidural anesthesia for hernioplasty in 37 patients aged from 3 months to 5 years. All patients were placed in the left lateral position. Conventional caudal epidural anesthesia was performed on one group of patients (Group C) using a 23 gauge needle (25 mm in length). This new method was also performed on another group (Group N) using a 23 gauge Teflon cannula (63 mm in length), which was introduced as close to the S1 segment as possible. The volume for 9 segmental anesthesia (7.0 +/- 2.3 ml) was determined by following Takino's formula: Volume (ml.segmental-1) = 0.067 x [body weight (kg)] + 0.06. The amount was injected from the S1 in Group N patients, and the cephalad spread of the anesthetic reached Th12.8 +/- 0.8 on left side, and L1.1 +/- 0.7 on right side. When the volume for 13 segmental anesthesia (11.5 +/- 2.8 ml) was injected in Group C patients, the cephalad spread of the anesthetic reached Th12.6 +/- 1.2 on the left side, and Th12.5 +/- 1.1 on the right side. In conclusion, we detected no significant difference between Group C and Group N in the cephalad spread of the anesthetic. The required dose of local anesthetic for caudal epidural anesthesia using the Teflon cannula was about two-third the volume of that used for the conventional local anesthetic method.