Solution thermodynamics and solubilization behavior of diclofenac sodium in binary mixture of Transcutol-HP and water.

Solution thermodynamics and solubilization behavior of diclofenac sodium (DS) in binary mixture of Transcutol-HP and water is not reported in the literature so far. Therefore, the aim of the present study was to investigate the solution thermodynamics and solubilization behavior of DS in mono-solvents and various Transcutol-water mixtures at 298.15-333.15 K. The mole fraction solubility of DS was determined by shake flask method and thermodynamic parameters (enthalpies and entropies) were calculated with the help of the modified Apelblat model. The experimental solubility data of DS in all sample matrices was found to be correlated well with the modified Apelblat model with correlation coefficients of 0.9950-0.9990. Absolute relative deviation was found to be less than 3% in most of the Transcutol-water mixtures at each temperature studied. The mole fraction solubility of DS was observed to be highest in pure Transcutol (0.139 at 298.15 K) as compared to pure water and other Transcutol-water mixtures. The enthalpies and entropies for DS dissolution were observed as positive values for all cosolvent mixtures which indicated that the dissolution of DS is endothermic and an entropy-driven process. Based on solubility data, DS was considered as sparingly soluble in pure water and freely soluble in Transcutol. These results indicated that Transcutol could be used as an alternate of ethanol, propylene glycol and polyethylene glycol to enhance aqueous solubility of DS. These preliminary studies could be useful in formulation development of DS especially in terms of liquid dosage forms and injectable formulations.

Protective effects of Ocimum sanctum on lipid peroxidation and antioxidant status in streptozocin-induced diabetic rats.

The antioxidant effects of Ocimum sanctum in experimental streptozocin-induced diabetic rats was evaluated in this study. Streptozocin, 55 mg kg(-1) body weight, was injected intraperitoneally once daily for 30 days to induce diabetes mellitus in rats. Streptozocin-induced diabetic rats were orally treated with an aqueous extract of O. sanctum once daily for 30 days. After the experimental period, thiobarbituric acid reacting substances (TBARS) and antioxidant enzymes such as catalase, superoxide dismutase (SOD) and glutathione peroxidase were measured. Administration of O. sanctum to streptozocin-induced diabetic rats for 30 days significantly reduced the plasma level of TBARS and improved the status of the antioxidant enzymes catalase, SOD and glutathione peroxidase in vital organs such as the liver and kidney. These results confirmed that the Indian medicinal plant O. sanctum has a protective effect and it may be useful in controlling complications resulting from diabetes.

Anti-inflammatory and antioxidant activity of Ficus carica Linn. leaves.

Ficus carica Linn. (Moraceae) is commonly known as edible fig. The leaves, roots, fruits and latex of the plant are medicinally used in different diseases. The leaves are claimed to be effective in various inflammatory conditions like painful or swollen piles, insect sting and bites. However, there has been no report on anti-inflammatory and antioxidant activity of F. carica leaves. Therefore the aim of this study was to evaluate the anti-inflammatory and antioxidant activity of F. carica leaves. Our study validated the traditional claim with pharmacological data. Anti-inflammatory and antioxidant activity of the drug could be due to the presence of steroids and flavanoids, respectively, which are reported to be present in the drug. Furthermore, the anti-inflammatory activity of the drug could be due to its free radical scavenging activity. Further work is also required to isolate and characterise the active constituents responsible for the anti-inflammatory activities.

High-performance thin layer chromatographic quantification of bioactive psoralen and daidzein in leaves of Ficus carica L.

This study was undertaken to quantify psoralen and daidzein by high-performance thin layer chromatography (HPTLC). The methanolic extract of 10 mg mL(-1) concentration solution was prepared for HPTLC quantification of psoralen and daidzein. HPTLC aluminium-backed plates coated with 0.2 mm layers of silica gel 60 F(254) were used as the stationary phase. The working standard solution of psoralen and daidzein was applied along with the test sample solution by means of Camag Linomat IV sample applicator. R (f) values of psoralen and daidzein were found to be 0.60 and 0.88, whilst as their percentage values in methanolic extract were found to be 3.02% and 5.64% (w/w), respectively. A simple quantitative estimation method of psoralen and daidzein by HPTLC is reported that can be used for the quality control of marketed preparations containing Ficus carica. However, further study is warranted to isolate and quantify active constituents present in the leaves of F. carica by sophisticated techniques.

HPTLC densitometric analysis of arbutin in bulk drug and methanolic extracts of Arctostaphylos uva-ursi.

A high-performance thin layer chromatographic densitometric method for the analysis of arbutin was developed and validated in the present investigation. Arbutin was separated on aluminium-backed silica gel 60 F(254) plates with methanol : chloroform (3:7)% (v/v) as the mobile phase. This system was found to give a compact spot of arbutin at a retention factor (R(f)) value of 0.32 ± 0.02. The limit of detection and limit of quantification were found to be 35.42 and 106.26 ng/spot, respectively. The proposed method with a high degree of precision and accuracy was employed for the analysis of arbutin in the bulk drug and methanolic extract of Arctostaphylos uva-ursi.

A new HPTLC densitometric method for analysis of swertiamarin in Enicostemma littorale and commercial formulations.

A high-performance thin layer chromatographic densitometric method for the analysis of swertiamarin in 60% methanolic extract of Enicostemma littorale and commercial formulations has been developed and validated in this study. Swertiamarin was separated on aluminium-backed silica gel 60 F254 plates using ethyl acetate : methanol : water (77 : 15 : 8)% v/v as the mobile phase. This system was found to give a compact spot of swertiamarin at R(f) value 0.36 ± 0.01. The limit of detection and limit of quantification were found to be 31.25 and 103.12 ng spot⁻¹, respectively. The proposed method was employed with a high degree of precision and accuracy for the estimation of swertiamarin in methanolic extract of Enicostemma littorale and in commercial formulations.

Pharmacokinetics of a losartan potassium released from a transdermal therapeutic system for the treatment of hypertension.

Monolithic transdermal therapeutic systems (TTS) were developed for sustained antihypertensive effect of losartan potassium using the polymers Eudragit E 100 and polyvinyl pyrrolidone VA 64. The developed formulations (polymeric films) were evaluated for physical characteristics, ex vivo (histopathology) and in vivo (pharmacokinetic studies). Pharmacokinetic parameters, such as C(max), t(max), and AUC were estimated. The transdermal formulation in the present study was found to enhance the relative bioavailability of losartan potassium by 2.2 times with reference to an oral delivery. The increased bioavailability might be due to elimination of hepatic first pass metabolism. Thus, the transdermal formulation F3E with polymeric composition of Eudragit E 100 and polyvinyl pyrrolidone VA 64 (5:3) was found to provide prolonged steady state concentrations of losartan potassium with minimal fluctuations and improved bioavailability.

Effect of vitamin C on lipidperoxidation and antioxidant status in tamoxifen-treated breast cancer patients.

BACKGROUND: Vitamin C is a water-soluble chain-breaking antioxidant that has beneficial effects on lipid-metabolizing enzymes. In the present study, the level of thiobarbituric acid (TBA) substances and antioxidant enzymes such as catalase, superoxide dismutase (SOD), glutathione peroxidase and glutathione-S-transferase were assayed. METHODS: The level of TBA substances and antioxidant enzymes was determined in plasma and RBC hemolysates, respectively, in 60 postmenopausal women with breast cancer. RESULTS: The data obtained from the study revealed that the levels of TBA and the antioxidant enzymes catalase, SOD, glutathine peroxidase and glutathine-S-transferse were significantly normalized by vitamin C treatment in the RBC hemolysate. CONCLUSION: The results compared vitamin C-treated breast cancer patients with normal individuals and showed that co-administration of vitamin C is more beneficial in breast cancer patients treated with tamoxifen.

Production, characterization, in vitro and ex vivo studies of babchi oil-encapsulated nanostructured solid lipid carriers produced by a hot aqueous titration method.

An aqueous dispersion of solid fat nanoparticles of babchi oil (BOSLN) was prepared by means of the hot water titration method. Surface morphology was determined by HR-TEM which revealed a fairly spherical shape of the formulations. Further they were evaluated for in vitro drug release characteristics and ex vivo skin permeation profile, zeta potential and particle diameter, rheological measures and droplet size distribution. Highest values for steady state flux (Jss), permeability coefficient (Kp) and enhancement ratio (Er) were observed for formulation, BOSLN3 comprised of oil [10% v/v; BO (3.33%), CAT (6.67%)], Tween 80 (9.25% v/v), transcutol-P (28.75% v/v) and distilled water (53% v/v). These results suggest that the studied SLN might be promising vehicles for babchi oil in the management of psoriasis.

Enhanced anti-inflammatory effects of celecoxib from a transdermally applied nanoemulsion.

The aim of the present study was to evaluate the enhanced anti-inflammatory effects of celecoxib (CXB) from a transdermally applied nanoemulsion. The anti-inflammatory effects of an optimized nanoemulsion formulation were compared with those of conventional CXB gel and nanoemulsion gel on carrageenan-induced paw edema in rats. These tests were compared using the Dunnett test of one-way analysis of variance (ANOVA). The % inhibition value after 24 h application was significant for optimized formulation C2 (85.4%) compared with CXB gel and nanoemulsion gel (p < 0.05). These results suggest that nanoemulsions can be successfully used to enhance the anti-inflammatory effects of CXB.

Effect of Labrasol on self-nanoemulsification efficiency of ramipril nanoemulsion.

The purpose of the present investigation was to evaluate the capacity of Labrasol as surfactant for self-nanoemulsification efficiency of ramipril nanoemulsion formulation. Based on the solubility profile of ramipril, Sefsol-218, Labrasol and Carbitol were selected as oil phase, surfactant and cosurfactant, respectively. Based on the stability profile of ramipril, standard buffer solution of pH 5.0 was selected as an aqueous phase for the development of ramipril nanoemulsion formulation. Nanoemulsion formulations of ramipril were developed using an aqueous phase titration method. Pseudoternary phase diagrams were constructed to identify the nanoemulsion region. Selected formulations were subjected to different thermodynamic stability tests using centrifugation, heating cooling cycles and freeze thaw cycles. The formulations which were stable at thermodynamic stability tests were taken for self-nanoemulsification efficiency test. No creaming, cracking, coalescence or phase inversion was observed on most of the formulations upon thermodynamic stability tests. All the formulations passed self-nanoemulsification tests in grade C, D and E but not in grade A and B. Because none of the formulation passed self-nanoemulsification efficiency test in grade A and B, it was concluded that Labrasol is not suitable as surfactant for oral or self nanoemulsifying drug delivery system of ramipril.

Potential of nanoemulsions for intravenous delivery of rifampicin.

The aim of the present study was to develop, characterize and evaluate nanoemulsion formulations for intravenous delivery of rifampicin (RIF). Different oil-in-water (o/w) nanoemulsions were prepared by the aqueous phase titration method. Prepared nanoemulsions were subjected to thermodynamic stability tests for phase separation, creaming, cracking, coalescence or phase inversion and dispersibility test for dilution capacity. Nanoemulsion formulations which passed these tests were characterized in terms of droplet size, viscosity, entrapment efficiency, homogeneity and pH. The selected formulations were subjected to in vitro dissolution studies using a dissolution apparatus-XXIII in dialysis bag. Best results were obtained with the formulation which consisted of 150 mg of RIF, 15% w/w of Sefsol 218, 18.75% w/w of Tween 80, 6.25% w/w of Tween 85 and 60% w/w of normal saline. The optimized formulation was also subjected to stability studies according to the ICH guidelines. The formulation was found to be stable for more than19 months. These results indicated the potential of nanoemulsions for intravenous delivery of RIF.

Skin permeation mechanism of aceclofenac using novel nanoemulsion formulation.

The aim of the present study was to investigate the skin permeation mechanism of aceclofenac using a novel nanoemulsion formulation. An optimized oil-in-water nanoemulsion of aceclofenac was prepared by the spontaneous emulsification method. The optimized nanoemulsion contained 2% w/w aceclofenac, 10% w/w Labrafil, 5% w/w Triacetin, 35.33% w/w Tween 80, 17.66% w/w Transcutol P and 32% w/w distilled water. The skin permeation mechanism was evaluated by FTIR spectroscopy, DSC thermography, activation energy measurement and histopathological examination. FTIR spectra of skin treated with the nanoemulsion formulation indicated breaking of the hydrogen bond network at the head of ceramides. DSC thermograms indicated that intracellular transport could be a possible mechanism of permeation enhancement and that permeation occurred due to the extraction of SC lipids by the nanoemulsion. The significant decrease in activation energy for aceclofenac permeation across rat skin indicated that the SC lipid bilayers were significantly disrupted (p < 0.05). Photomicrography of skin showed disruption and extraction of lipid bilayers as distinct voids and empty spaces visible in the epidermal region. Overall these findings indicated that nanoemulsions can be successfully used to enhance skin permeation of drugs.

Development and evaluation of a microemulsion formulation for transdermal delivery of terbinafine.

The aim of the present study is to develop and evaluate microemulsion formulations for Terbinafine (TB) with a view to enhance its permeability through the skin and provide release for 24 h. Various o/w microemulsions were prepared by the spontaneous emulsification method. Oleic acid was chosen as the oil phase, Caprylo caproyl macrogol-8- glyceride (Labrasol S) and purified diethylene glycol monoethyl ether (Transcutol P) were used as surfactant and cosurfactant, respectively, on the basis of solubility studies. Pseudoternary phase diagrams were constructed to obtain the concentration range of oil, surfactant, cosurfactant, and water for microemulsion formulation. The optimized microemulsion consisted of 2% w/w TB, 8% w/w oleic acid, 31% w/w labrasol S, 31% w/w transcutol P, and 30% w/w distilled water. Permeability parameters like Jss and Kp were found to be significantly higher for formulation F4 as compared to other formulations (P < 0.05). Microbiological studies of TB in microemulsion showed better anti-fungal activity against Candida albicans and Aspergillus flavus as compared to marketed product (P < 0.05).

Formulation and evaluation of once-a-day transdermal gels of diclofenac diethylamine.

The present study was undertaken to prepare and evaluate transdermal gels of diclofenac diethylamine (DDEA) containing penetration enhancers such as olesan oil and dimethyl sulfoxide (DMSO). Transdermal gels were prepared using different polymers such as carbopol-940, polyvinyl alcohol (PVA), hydroxy propyl methyl cellulose-K(4) M, hydroxy propyl cellulose-M, and sodium carboxy methyl cellulose. The formulated gels were subjected to physicochemical studies, in vitro release studies and in vitro skin permeations studies and were evaluated for drug content, viscosity, extrudability, spreadability, and pH. The in vitro release studies of prepared gels were performed using specially designed Fites cell and in vitro skin permeation studies were performed using keshary-chien diffusion cell through rat skin. Selected formulations were evaluated for their antiinflammatory activity using the carrageenan-induced paw edema in rats. The carbopol-940 and PVA gels containing 10% DMSO showed best in vitro skin permeation of DDEA. In vivo study for the selected formulation showed a sustained reduction in inflammation in the carrageenan induced paw edema in rats. The efficacies of carbopol-940 and PVA gels were also compared with that of the marketed Voveran gel,(R) and it was found that carbopol and PVA gels produced better results than the Voveran gel. (c) 2006 Prous Science. All rights reserved.

Extreme torsion of the pregnant uterus.

Extreme uterine torsion of 180 degrees at term is a rare obstetric event and raises several critical management considerations. We report such a case detected at laparotomy for a repeat Caesarean section. The existing literature on uterine torsion is reviewed and a plan of management is suggested, based on previous reports and our own experience.