Analysis of calcium channel blocking dihydropyridines by high performance liquid chromatography.

Nine dihydropyridine calcium blockers have been analyzed by HPLC .Symultaneous analysis has been performed both using different isocratic conditions and linear gradient method . The influence of pH and ionic strength of the mobile phase on separation mechanism is discussed. Moreover, the separation ability of original compounds from daylight degradation products has been studie

Inhibition of butyrylcholinesterase by organophosphorus compounds: a quantitative structure-activity analysis.

Quantitative structure-activity relationships have been formulated for the interactions of a variety of inhibitors with butyrylcholinesterase. The parameters KQ, k2 and ki are found to be strongly dependent on molar refractivity as well as on the inductive effect of the leaving group --SR' in structures of the RO (X) P (O) SR' type. A model for the interaction of organophosphorus compounds is presented which gives a consistent view of the binding step, acylation and overall inhibition

Quantitative structure-activity relationships in a set of antimuscarinic agents.

Quantitative structure-activity relationships (QSAR) have been formulated for the interactions of a set of antimuscarinic agents. The antagonistic activity is found to be dependent on hydrophobic-lipophilic character and steric requirements of substituents R1 and R2 in structures of type R1R2N--CH2--CH2--+NR3R4R5. Moreover, it is shown that the incumbrance of R3, R4 and R5 groups and their polar effects on the onium ending greatly affect the antagonistic activity. A binding model which suggests new avenues for exploration is presented

Penetration enhancement of ibuprofen from supersaturated solutions through human skin.

Systematic investigations on the diffusion of ibuprofen (IBU) from supersaturated solutions through human epidermis are reported. Significant flux enhancement was obtained from supersaturated solutions compared to the saturated solution. Hydroxypropyl methylcellulose (HPMC), when used as an additive was found to be effective in maintaining the high activity state at high degrees of saturation (DS). The increase in the flux was proportional to the DS. In the presence of 2-hydroxypropyl-beta-cyclodextrin (CD) at DS 2 and 3 a lower flux was observed compared to HPMC. At DS 5 a higher flux enhancement was found suggesting that CD might act as a penetration enhancer at certain CD/drug ratios. Studies on the mechanism of stabilisation of HPMC and CD on IBU crystallisation from supersaturated systems showed that HPMC acts as a growth inhibitor and habit modifier whereas CD does not influence the crystallisation process

Combined effect of hydroxypropylmethylcellulose and hydroxypropyl-beta-cyclodextrin on physicochemical and dissolution properties of celecoxib

Investigation on the influence of hydroxypropyl methylcellulose (HPMC) on solubility and dissolution properties of celecoxib/hydroxypropyl-β-cyclodextrin system was carried out, with the ultimate goal of enhancing the drug bioavailability. 1H-NMR and 13C-NMR spectroscopy were first performed to elucidate the type of interactions between celecoxib (CEL) and hydroxypropyl-β-cyclodextrin (HP-β-CD). Then, solubility studies in the absence and in the presence of HPMC were carried out in aqueous solution. After heating in autoclave of CEL/HP-β-CD/HPMC suspensions a synergistic increasing effect on the aqueous solubility of CEL was observed. In fact, the presence of both HP-β-CD (0.05 M) and HPMC (0.25% w/v) gave rise to a 330-fold CEL solubility increase, whereas the cyclodextrin alone provided a 34-fold increase. Gibbs free energy values calculated from phase solubility data were all negative, indicating the spontaneous nature of CEL solubilization, and they decreased in the presence of HPMC, demonstrating that the solubilization conditions became more favorable. CEL/HP-β-CD and CEL/HP-β-CD/HPMC solid systems (physical mixtures and coevaporated products) were characterized by differential scanning calorimetry and infrared spectroscopy. Results suggested that the coevaporation method yields a high degree of amorphous entities and indicated the formation of a CEL/HP-β-CD complex in the coevaporated products. The positive effect of HPMC is particularly evident when looking at the CEL dissolution rate from the binary and ternary solid systems. Specifically, the percent of CEL dissolved after 10 min. resulted 84.21% for ternary coevaporated product and 50.18% for binary coevaporated product with respect to 13.10% for the drug alone

Chromatographic indexes on immobilized artificial membranes for the prediction of transdermal transport of drugs.

A set of 12 drugs, consisting of structurally unrelated neutral, basic, acidic and amphoteric compounds, was examined by high performance liquid chromatrography (HPLC) on a model of fluid membrane bilayers, the immobilized artificial membrane (IAM) column. The logarithms of chromatographic capacity factors extrapolated to 100\% aqueous phase at pH 5.5 (log kw) were measured and compared to the n-octanol/water partition coefficients (log P). The scale derived from the IAM system was different from the lipophilicity scale expressed by the log P, due to the peculiar capability of phospholipids to well accommodate the ionized form of some molecules and show additive or repulsive extra-interactions when particular structural motifs on the molecule are present. The relationship between log P and log kw previously obtained for compounds interacting on IAM phase by a uniquely lipophilicity-based mechanism, allowed us to calculate, from log P, the values of log kw expected for the drugs considered. These values were subtracted from the log kw experimentally determined and the differences were assumed to quantify the amount of extra-interactions (hydrogen bond and electrostatic interactions) with phospholipids (delta log kw). The coefficients of permeability through the human skin (Kp) for the compounds considered did not correlate with either log kw or log P values. However, the Kp values correlated well with the delta log kw values indicating that the higher the ability of a molecule to cross the skin barrier, the lower its component of interaction with phospholipids not accounted for by lipophilicity-based interactions