Antioxidant and hepatoprotective effects of silymarin phytosomes compared to milk thistle extract in CCl4 induced hepatotoxicity in rats.

Milk thistle extract is a well-known hepatoprotectant with low bioavailability (20-50%). The objective of the present study is to prepare and characterize silymarin phytosomes and to test the hepatoprotective effect of the phytosomes in CCl4 induced liver injury in rats compared to milk thistle extract. Phytosomes were prepared using lecithin from soybeans and from egg yolk. The prepared phytosomes were examined using scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy (H(1)NMR). The loading efficiency was >85% in all phytosomal formulations. Formula P2 (with the molar ratio of soybean lecithin to silybin 1:1) and P4 (with the molar ratio of egg-yolk lecithin to silybin 0.25:1) exhibited significantly (p < 0.05) faster release than milk thistle extract. The in vivo study revealed that phytosomes significantly (p < 0.05) decreased glutamic pyruvic transaminase and super oxide dismutase activities compared to milk thistle extract.

Formulation of microemulsion gel systems for transdermal delivery of celecoxib: In vitro permeation, anti-inflammatory activity and skin irritation tests.

The aim of this study was to develop suitable microemulsion gel systems for transdermal delivery that could assist dissolution enhancement of poorly water soluble celecoxib and thus improve its skin permeability. Long term oral administration of celecoxib causes serious gastrointestinal adverse effects, which makes it a good candidate for transdermal formulations, yet its low water solubility (4 mg/L) makes this challenging. Ternary phase diagrams were constructed using isopropyl myristate and oleic acid as oils, Tween 80 as surfactant, and Cremophor RH40 as cosurfactant. Microemulsion areas were identified and two systems each of 36 formulas were prepared and assessed for visual inspection, spreadability, pH measurements, and droplet size analysis. Drug release and in vitro permeation of celecoxib from microemulsion formulas through semi-permeable membranes and excised abdominal rabbit skin, respectively, were carried out and compared to celecoxib cream. In all tested formulas, celecoxib was released and permeation was at a higher rate than that from the corresponding cream. The optimized formula (F12) was found to be superior to all other formulas. This formula increased the permeation rate of celecoxib up to 11 times compared to that of the cream. Its stability was retained after one year of storage under ambient conditions and its anti-inflammatory effect was significantly higher than that of celecoxib cream and the oral commercial formula. Skin irritancy and histopathological investigation of rat skin revealed its safety. The results revealed that the developed microemulsion gel has great potential for transdermal delivery of celecoxib.

Comparative study on the different techniques for the preparation of sustained-release hydrophobic matrices of a highly water-soluble drug.

The objective of the present study was to control the release of freely water-soluble salbutamol sulphate (SS) over a prolonged period of time by embedding the drug into slowly eroding waxy matrix materials such as Precirol® ATO5, Compritol® 888 ATO, beeswax, paraffin wax, carnauba wax, and stearyl alcohol. The matrices were prepared by either direct compression or hot fusion techniques. The compatibility of the drug with the various excipients was examined using differential scanning calorimetry (DSC). A factorial design was employed to study the effect of polymer type, polymer concentration (15% and 35%), and filler type (Avicel® PH101 and dibasic calcium phosphate dehydrate (DCP) on the in vitro drug release at 6 h. Results of DSC confirmed drugexcipient compatibility. Increasing the polymer ratio resulted in a significant retardation of drug release. The use of DCP resulted in significant retardation and incomplete drug release while the use of Avicel did not. The hot fusion method was found to be more effective than the direct compression method in retarding SS release. A Precirol formulation, prepared using the hot fusion technique, had the slowest drug release, releasing about 31.3% of SS over 6 h. In contrast, Compritol, prepared using the direct compression technique, had the greatest retardation, providing sustained release of 59.3% within 6 h. A hydrophobic matrix system is thus a useful technique for prolonging the release of freely water-soluble drugs such as salbutamol sulphate.

Characterization and evaluation of tenoxicam coprecipitates.

Tenoxicam is a nonsteroidal anti-inflammatory drug belonging to the oxicam group. The drug is slightly soluble in water. In a trial to increase its dissolution, different commonly used excipients were selected to prepare coprecipitates with tenoxicam. The coprecipitates were prepared using the solvent evaporation method, and the ratio used was 1:3 drug to additive. The prepared coprecipitates were subjected to a dissolution study, and they were characterized using infrared (IR) and differential scanning calorimetry (DSC) techniques. Dissolution profiles of most of the prepared coprecipitates demonstrated higher dissolution than pure tenoxicam. The characteristic peaks of tenoxicam in the IR spectrum disappeared in the spectra of all the prepared coprecipitates except those prepared with sodium chloride, for which the IR spectrum was identical to that of the pure drug. The characteristic peaks of tenoxicam disappeared in the DSC thermograms of the coprecipitates under study, indicating a change in structure from pure tenoxicam. Characterization of the coprecipitates by IR and DSC techniques revealed structural changes in the prepared coprecipitates from the plain drug, which may account for increased dissolution rates.