DARU, Journal of Pharmaceutical Sciences
Volume:8 Issue: 4, winter 2000

Partial phase diagrams were constructed at 25°C to investigate the phase behaviour of systems composed of soybean lecithin, water, sodium salicylate, alcohol and isopropyl myristate. The lecithins used were the commercially available soy bean lecithins, namely E200 and E170 (phosphatidyl choline purities greater than 95% and 68-72% respectively). The cosurfactants employed were n-propanol, 2-propanol and n-butanol and these were used at lecithin/alcohol weight ratios (Km) of 1:1 and 1.5:1. At a given Km, the aqueous phase consisted of a 2% w/w sodium salicylate solution. Phase diagrams showed the area of existence of a stable isotropic region along the surfactant/oil axis (i.e., reverse microemulsion area). The extension of the microemulsion domain was influenced by the purity of surfactant, the lecithin/alcohol weight ratios and the kind of the alcohol.

The available theoretical and empirical models for expression a solute solubility in a binary solvent system as a function of the solvent concentration have been compared by the accuracy and predictability points of view. In order to evaluate the accuracy of the equations with different number of curve fitting parameters, 3 to 7 parameter models from the considered methods were employed using whole data points in each set. In addition, a minimum number of 3 and/or 5 data point were used to calculate the model parameters from which the whole data points in each set was predicted. Using the whole data in a set, it became evident that no single model was superior in all aspects of accuracy. However, one of the models in which the number of data expressed as percentage of all data points in all sets was adhered best whereas another model was the best when the percent overall average error for all the set was used as a measure of accuracy. When a minimum number of data in a set was employed to estimate model constants for evaluating the predictability, it became apparent that those produced accurate results when the whole data points did not yield satisfactory predictions and other models were superior in this respect.

In this research, several formulations containing, an anti emetic agent (Metoclopramide hydrochloride), a hydrophilic polymer (hydroxypropylmethylcellulose) and a hydrophobic polymer (ethylcellulose 10 cP) were prepared by direct compression. Different factors such as: the effect of different ratios of the polymers, particle size, pressure force and differences of release in acidic and distilled water as media were investigated. After developing the ideal formulation, the effect of changing the ratio of drug in core: coating on the formulation was investigated. Coating of tablets with ethylcellulose, changed the release mechanism of drug and shifted it to near zero order release. The results showed that except when matrices were coated with ethylcellulose, drug release was proportioned to the square root of time, which might be due to the change of release pattern from matrix to reservoir system.

The mechanical strength of different material composite beams were assessed. All tablets were subjected to three-point bending test. For the preparation of tablets, the material of the lower layer was initially put in the die and compacted by a certain pressure. The second material was then put upon the first layer. Modulus of elasticity of the selected materials were used to interpret the behaviour of the top and bottom layers of the different materials composite tablets. Determination of the strength at the highest and lowest point of different material composite beams, showed that if the material with higher modulus of elasticity was placed at the lower layer, the value of compressive strength (σc) obtained from exerting fracture load at the higher point, was more than the value obtained at the lower point (i.e. tensile strength, σf). On the other hand, if the material of higher modulus of elasticity E, was located at the top surface, the stress value at the lower layer (σf) was more than its value at the higher layer (i.e. σc). The range of σc/σf was 1/3, if number of components (n) was much more than one. Inversely, when ‘n’ was less than 1, the value for σc/σf was near 3.

Altered functions of mesangial cells induced by high glucose concentrations are thought to play an important role in the pathogenesis of diabetic nephropathy. We therefore investigated the effect of high glucose (39.2 mM) alone and in combination with taurine (500 µM) or vitamin E (100 µM) in serum free medium (RPMI 1640) on the proliferative growth response and turnover of type IV collagen by human glomerular mesangial cells (GMC). The results showed that the high glucose level decreases the proliferation of the GMC which is reversed by taurine and vitamin E. In order to control the osmotic effects of high glucose, the GMC were also cultured in the presence of manitol. Manitol had no effect on the proliferation of GMC. Furthermore, the results showed that addition of vitamin E or taurine to media containing high glucose could reverse and normalize the collagen turn-over by the cultured mesangial cells. These results suggest that taurie and vitamin E may function as endogenous agents in the kidney to limit the development of glomerulosclerosis in diabetic renal disease.

Various diester analogues of nifedipine in which the ortho nitrophenyl group at position 4 were replaced by 3-chloro-1H-2-indolyl substituent, were synthesized and evaluated as calcium antagonists on guinea-pig ileal smooth muscle. Nifedipine was used as a standard. Compound 6f was found to be the most active.

The preparation of 1-anthroyl nitrile as a useful labeling reagent for derivatization of hydroxysteroids is reported. This compound was prepared by some modifications in the literature procedure including the usage of copper cyanide instead of the expensive trimethylsilyl cyanide for conversion of 1-anthroyl chloride to 1-anthroyl nitrile and conducting the conversion of anthracene-1-carboxylic acid to 1-anthroyl chloride at 40°C instead of 110°C to avoid the formation of impurities. Derivatization of cortisol and prednisolone by 1-anthroyl nitrile resulted in effective separation of these compounds by HPLC with a detection limit of about 20 pg.

The interaction of hamalol with calf-thymus DNA was investigated at physiological pH with drug/DNA (phosphate) molar ratio(r) of 1/40. Fourier transform infrared difference spectroscopy were used to establish correlations between spectral changes and drug binding mode, sequence selectivity, DNA conformation and structural properties of harmalol-DNA complexes in aqueous solution. Spectroscopic results indicated that harmalol is a weak intercalator with affinity for A-T rich regions. At low drug concentration (r=1/40), the A-T region is the main target of drug intercalation.

Carnosol was isolated form the aerial parts of Salvia eremophila Boiss and full assignments of ¹H and ¹³C-NMR spectral data are presented.