Theoretical explanation for the pharmaceutical incompatibility through the cooperativity effect of the drug-drug intermolecular interactions in the phenobarbital∙∙∙paracetamol∙∙∙H2O complex.

In order to reveal the essence of the pharmaceutical incompatibility, the cooperativity effects of the drug-drug intermolecular π∙∙∙π and H∙∙∙O H-bonding interactions involving hydration were evaluated in the phenobarbital∙∙∙paracetamol∙∙∙H2O complex at the M06-2X/6-311++G** and MP2/6-311++G** levels. The thermodynamic cooperativity effects were also investigated by the statistical thermodynamic method. The results show that the π∙∙∙π stacking ternary complexes with the moderate anti-cooperativity effects are dominant in controling the aggregation process of phenobarbital, paracetamol, and H2O, as is confirmed by the atoms-in-molecules (AIM) and reduced density gradient (RDG) analyses. Therefore, it can be inferred that the anti-cooperativity effect plays an important role in forming the pharmaceutical incompatibility, and thus a deduction on the formation process of the pharmaceutical incompatibility between phenobarbital and paracetamol, with the hydration effect, is given. Several valuable models that relate the features of molecular surface electrostatic potentials or their statistical parameters, such as the surface areas, average values ([Formula: see text]), variances ([Formula: see text], [Formula: see text] and [Formula: see text]), and product of [Formula: see text] and electrostatic balance parameter (ν) ([Formula: see text]ν), to the values of the cooperativity effects were predicted. The formation of the pharmaceutical incompatibility is a thermodynamic cooperativity process driven by the enthalpy change. Graphical abstract Anti-cooperativity effect plays an important role in forming the pharmaceutical incompatibility.

Potency fingerprint of herbal products Danshen injection for their quality evaluation.

The fingerprint technique has been studied frequently as a useful strategy for quality of traditional Chinese medicine. A novel potency fingerprint that can quantitatively analyze the antioxidant activity of individual constituent and provide the total antioxidant activities of the samples has been developed by high-performance liquid chromatography coupled with ultraviolet and pyrogallol-luminol chemiluminescence detection (HPLC-diode array detection (DAD)-PLD). Hierarchical clustering analysis has been used as a powerful pattern recognition tool to identify and classify Danshen injection from different factories. In addition, the combination use of the chromatographic fingerprint and potency fingerprint with principal component analysis was applied to quality control of Danshen injection. The results demonstrated that the proposed potency fingerprint was a useful means to control the quality and to clarify the possible mechanism of action of herbal products.

Pharmacological interventions for the treatment of neonatal jaundice.

In the neonate, hyperbilirubinaemia is usually due to a combination of an increased bilirubin load and decreased bilirubin elimination. Despite an understanding of the enzymatic pathways leading to bilirubin production and elimination, very few pharmacological interventions to prevent hyperbilirubinaemia are utilized and the mainstay of treatment remains phototherapy. Previously studied pharmacological agents such as D-penicillamine, phenobarbital and clofibrate may yet prove useful. Recent clinical trials using metalloporphyrins to inhibit heme catabolism and bilirubin production provides a novel pharmacological intervention for the treatment of neonatal jaundice. The safety and efficacy of these therapies will need to be confirmed prior to widespread use.

Effect of nonionic surfactant on transport of surface-active and non-surface-active model drugs and emulsion stability in triphasic systems.

The effect of surfactant concentration on transport kinetics in emulsions using surface-active (phenobarbital, barbital) and non- surface-active (phenylazoaniline, benzocaine) model drugs is determined. Mineral oil was chosen as the oil phase and the nonionic surfactant polyoxyethylene-10-oleyl-ether (Brij 97) was chosen as the emulsifier. Model drug transport in the triphasic systems was investigated using side-by-side diffusion cells mounted with hydrophilic dialysis membranes (molecular weight cutoffs 1 kd and 50 kd) and a novel bulk equilibrium reverse dialysis bag technique. Emulsion stability was determined by droplet size analysis as a function of time, temperature, and the presence of model drugs, using photon correlation spectroscopy. Mineral oil/water (O/W) partition coefficients and aqueous solubilities were determined in the presence of surfactant. The transport rates of model drugs in emulsions increased with an increase in Brij 97 micellar concentrations up to 1.0% wt/vol and then decreased at higher surfactant concentrations. The transport profiles of the model drugs appeared to be governed by model drug O/W partition coefficient values and by micellar shape changes at higher surfactant concentrations. Total transport rates of phenobarbital and barbital were faster than those of phenylazoaniline and benzocaine. Excess surfactant affected the transport rates of the model drugs in the emulsions depending on drug surface activity and lipophilicity.

Mathematical modeling of surface-active and non-surface-active drug transport in emulsion systems.

Mathematical models were developed for the prediction of surface-active and non- surface-active drug transport in triphasic (oil, water, and micellar) emulsion systems as a function of micellar concentration. These models were evaluated by comparing experimental and simulated data. Fick's first law of diffusion with association of the surface-active or complexation nature of the drug with the surfactant was used to derive a transport model for surface-active drugs. This transport model assumes that the oil/water (O/W) partitioning process was fast compared with membrane transport and therefore drug transport was limited by the membrane. Consecutive rate equations were used to model transport of non-surface-active drugs in emulsion systems assuming that the O/W interface acts as a barrier to drug transport. Phenobarbital (PB) and barbital (B) were selected as surface-active model drugs. Phenylazoaniline (PAA) and benzocaine (BZ) were selected as non- surface-active model drugs. Transport studies at pH 7.0 were conducted using side-by-side diffusion cells and bulk equilibrium reverse dialysis bag techniques. According to the surface-active drug model, an increase in micellar concentration is expected to decrease drug-transport rates. Using the Microsoft EXCEL program, the non-surface-active drug model was fitted to the experimental data for the cumulative amount of the model drug that disappeared from the donor chamber. The oil/continuous phase partitioning rates (k1) and the membrane transport rates (k2) were estimated. The predicted data were consistent with the experimental data for both the surface-active and non- surface-active models.