Dissolution and bioavailability improvement of bioactive apigenin using solid dispersions prepared by different techniques.

Apigenin (APG) is a poorly soluble bioactive compound/nutraceutical which shows poor bioavailability upon oral administration. Hence, the objective of this research work was to develop APG solid dispersions (SDs) using different techniques with the expectation to obtain improvement in its in vitro dissolution rate and in vivo bioavailability upon oral administration. Different SDs of APG were prepared by microwave, melted and kneaded technology using pluronic-F127 (PL) as a carrier. Prepared SDs were characterized using "thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier transform infra-red (FTIR) spectrometer, powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM)". After characterization, prepared SDs of APG were studied for in vitro drug release/dissolution profile and in vivo pharmacokinetic studies. The results of TGA, DSC, FTIR, PXRD and SEM indicated successful formation of APG SDs. In vitro dissolution experiments suggested significant release of APG from all SDs (67.39-84.13%) in comparison with control (32.74%). Optimized SD of APG from each technology was subjected to in vivo pharmacokinetic study in rats. The results indicated significant improvement in oral absorption of APG from SD prepared using microwave and melted technology in comparison with pure drug and commercial capsule. The enhancement in oral bioavailability of APG from microwave SD (319.19%) was 3.19 fold as compared with marketed capsule (100.00%). Significant enhancement in the dissolution rate and oral absorption of APG from SD suggested that developed SD systems can be successfully used for oral drug delivery system of APG.

Multi-Layer Self-Nanoemulsifying Pellets: an Innovative Drug Delivery System for the Poorly Water-Soluble Drug Cinnarizine.

Beside their solubility limitations, some poorly water-soluble drugs undergo extensive degradation in aqueous and/or lipid-based formulations. Multi-layer self-nanoemulsifying pellets (ML-SNEP) introduce an innovative delivery system based on isolating the drug from the self-nanoemulsifying layer to enhance drug aqueous solubility and minimize degradation. In the current study, various batches of cinnarizine (CN) ML-SNEP were prepared using fluid bed coating and involved a drug-free self-nanoemulsifying layer, protective layer, drug layer, moisture-sealing layer, and/or an anti-adherent layer. Each layer was optimized based on coating outcomes such as coating recovery and mono-pellets%. The optimized ML-SNEP were characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), in vitro dissolution, and stability studies. The optimized ML-SNEP were free-flowing, well separated with high coating recovery. SEM showed multiple well-defined coating layers. The acidic polyvinylpyrrolidone:CN (4:1) solution presented excellent drug-layering outcomes. DSC and XRD confirmed CN transformation into amorphous state within the drug layer. The isolation between CN and self-nanoemulsifying layer did not adversely affect drug dissolution. CN was able to spontaneously migrate into the micelles arising from the drug-free self-nanoemulsifying layer. ML-SNEP showed superior dissolution compared to Stugeron® tablets at pH 1.2 and 6.8. Particularly, on shifting to pH 6.8, ML-SNEP maintained > 84% CN in solution while Stugeron® tablets showed significant CN precipitation leaving only 7% CN in solution. Furthermore, ML-SNEP (comprising Kollicoat® Smartseal 30D) showed robust stability and maintained > 97% intact CN within the accelerated storage conditions. Accordingly, ML-SNEP offer a novel delivery system that combines both enhanced solubilization and stabilization of unstable poorly soluble drugs.

Development and validation of bioanalytical UHPLC-UV method for simultaneous analysis of unchanged fenofibrate and its metabolite fenofibric acid in rat plasma: Application to pharmacokinetics.

A simple, precise, selective and fast ultra-high performance liquid chromatography (UHPLC-UV) method has been developed and validated for the simultaneous determination of a lipid regulating agent fenofibrate and its metabolite fenofibric acid in rat plasma. The chromatographic separation was carried out on a reversed-phase Acquity® BEH C18 column using methanol-water (65:35, v/v) as the mobile phase. The isocratic flow was 0.3 ml/min with rapid run time of 2.5 min and UV detection was at 284 nm. The method was validated over a concentration range of 100-10000 ng/ml (r2 â©¾ 0.9993). The selectivity, specificity, recovery, accuracy and precision were validated for determination of fenofibrate/fenofibric acid in rat plasma. The lower limits of detection and quantitation of the method were 30 and 90 ng/ml for fenofibrate and 40 and 100 ng/ml for fenofibric acid, respectively. The within and between-day coefficients of variation were less than 5%. The validated method has been successfully applied to measure the plasma concentrations in pharmacokinetics study of fenofibrate in an animal model to illustrate the scope and application of the method.

Hepatoprotective activity of Lepidium sativum seeds against D-galactosamine/lipopolysaccharide induced hepatotoxicity in animal model.

BACKGROUND: Fulminant hepatic failure (FHF) is clinical syndrome with very poor prognosis and high mortality there is urgent need for the development of safe and non-toxic hepatoprotective agents for the adequate management of hepatitis. Hepatoprotective effect of the Lepidium sativum ethanolic extract (LSEE) was assessed by D-galactosamine-induced/lipopolysaccharide (400 mg/kg and 30 µg/kg) liver damage model in rats. METHODS: Hepatoprotective activity of LSEE (150 and 300 mg/kg) and silymarin on D-GalN/LPS induced FHF in rat was assessed using several liver function enzyme parameters. Antioxidant properties as antioxidant stress enzymes were assessed in hepatic Liver as well as mRNA expression of cytokines genes such as TNF-α, IL-6, and IL-10 and stress related genes iNOS and HO-1 were determined by RT-PCR. Protein expression of apoptotic genes were evaluated through western blot. MPO and NF-κB DNA-binding activity was analyzed by ELISA. The magnitude of hepatic impairment was investigated through histopathological evaluation. RESULTS: Marked amelioration of hepatic injuries by attenuation of serum and lipid peroxidation has been observed as comparable with silymarin (25 mg/kg p.o). D-GalN/LPS induced significant decrease in oxidative stress markers protein level, and albumin. LSEE significantly down-regulated the D-GalN/LPS induced pro-inflammatory cytokines TNFα and IL-6 mRNA expression in dose dependent fashion about 0.47 and 0.26 fold and up-regulates the IL-10 by 1.9 and 2.8 fold, respectively. While encourages hepatoprotective activity by down-regulating mRNA expression of iNOS and HO-1. MPO activity and NF-κB DNA-binding effect significantly increased and was mitigated by LSEE in a dose-dependent style as paralleled with silymarin. CONCLUSION: Our data suggests that pretreatment of LSEE down regulates the caspase 3 and up-regulates the BCl2 protein expression. The above findings revealed that Lepidium sativum has significant hepatoprotective activity.

Hepatoprotective effect of Commiphora myrrha against d-GalN/LPS-induced hepatic injury in a rat model through attenuation of pro inflammatory cytokines and related genes.

CONTEXT: Commiphora myrrha (Burseraceae), a shrub resembling a small tree, has been used for several centuries for the treatment of various diseases. OBJECTIVE: This study investigates the hepatoprotective activity of C. myrrha ethanol extract against d-galactosamine/lipopolysaccharide (d-GalN/LPS)-induced acute hepatic injury in an animal model. MATERIALS AND METHODS: Rats were pretreated with ethanolic extract C. myrrha (250 and 500 mg/kg; p.o.) for 7 d prior to the induction of an acute phase response by d-GalN/LPS. Animals were sacrificed 24 h after d-GalN/LPS (800 mg/kg and 50 µg/kg i.p.) administration for the biochemical and histological analyses. RESULTS: The administration of d-GalN/LPS increased plasma aminotransferases (174.47 ± 4.5761 and 260.96 ± 1.9839 µkat/l) and total bilirubin levels (1.012 ± 0.0288 mg/dl), which were attenuated by C. myrrha treatment. Hepatic lipid peroxidation activity and nitric oxide content also increased, while the antioxidant activity measured by GSH (0.76 nmol/g protein), SOD (81.91 U/mg protein), and CAT (15.78 U/mg protein) was reduced. Commiphora myrrha provided significant restoration of GSH (0.815 nmol/gm protein), SOD (140.57 U/mg protein), and CAT (27.02 U/mg protein) levels. Furthermore, the acute phase response elicited by d-GalN/LPS administration enhanced mRNA expressions of TNF-α, IL-6, IL-10, iNOS-2, and HO-1, which were ameliorated by C. myrrha treatment. DISCUSSION AND CONCLUSION: These findings indicate that C. myrrha considerably reduces the oxidative stress of d-GalN/LPS-induced hepatic injury via multiple pathways including adown regulation of inflammatory mediators and cytokines. Such a property might be sufficient to combat cellular damage caused by various conditions that resemble fulminant hepatitis and could be of a potential clinical application.

Rapid and sensitive bioanalytical stability-indicating method for quantification of talinolol, a selective ß1 adrenoceptor antagonist in lipid based formulations using ultrafast UHPLC systems.

The current study evaluates the ultra high performance liquid chromatography (UHPLC) method for the quantification of talinolol in lipid-based formulations. A simple, rapid, reliable and precise reversed phase UHPLC method has been developed and validated according to the regulatory guidelines, which was composed of isocratic mobile phase; acetonitrile and phosphate buffer saline (pH 4.5) with a flow rate of 0.4 mL/min, and column HSS C18 (2.1 x 50 mm, 1.8 µm). The detection was carried out at 245 nm. The developed UHPLC method was found to be rapid (1.8 min run time), selective with high resolution of talinolol peak (0.88 min) from different lipid matrices and highly sensitive (limit of detection and lower limit of quantification were 0.14 ppm and 0.5 ppm, respectively). The linearity, accuracy and precision were determined as acceptable over the concentration range of 0.5-100 ppm for talinolol. The results showed that the proposed UHPLC method can be used for the estimation of talinolol in lipid-based formulation by indicating its purity and stability with no interference of excipients or related substances of active pharmaceutical ingredient.

Design of lipid-based formulations for oral administration of poorly water-soluble drug fenofibrate: effects of digestion.

Lipid-based drug carriers are likely to have influence on bioavailability through enhanced solubilization of the drug in the gastrointestinal tract. The study was designed to investigate the lipid formulation digestibility in the simulated gastro intestinal media. Fenofibrate was formulated in representative Type II, IIIA, IIIB and IV self-emulsifying/microemulsifying lipid delivery systems (SEDDS and SMEDDS designed for oral administration) using various medium-chain glyceride components, non-ionic surfactants and cosolvents as excipients. Soybean oil was used only as an example of long-chain triglycerides to compare the effects of formulation with their counterparts. The formulations were subjected to in vitro digestion specifically to predict the fate of the drug in the gastro intestinal tract after exposure of the formulation to pancreatic enzymes and bile. In vitro digestion experiments were carried out using a pH-stat maintained at pH 7.5 for 30 min using intestinal fluids simulating the fed and fasted states. The digestion rate was faster and almost completed in Type II and IIIA systems. Most of the surfactants used in the studies are digestible. However, the high concentration of surfactant and/or cosolvent used in Type IIIB or IV systems lowered the rate of digestion. The digestion of medium-chain triglycerides was faster than long-chain triglycerides, but kept comparatively less drug in the post digestion products. Medium-chain mixed glycerides are good solvents for fenofibrate as rapidly digested but to improve fenofibrate concentration in post digestion products the use of long-chain mixed glycerides are suggested for further investigations.

The studies of phase equilibria and efficiency assessment for self-emulsifying lipid-based formulations.

The study was designed to build up a database for the evaluation of the self-emulsifying lipid formulations performance. A standard assessment method was constructed to evaluate the self-emulsifying efficiency of the formulations based on five parameters including excipients miscibility, spontaneity, dispersibility, homogeneity, and physical appearance. Equilibrium phase studies were conducted to investigate the phase changes of the anhydrous formulation in response to aqueous dilution. Droplet size studies were carried out to assess the influence of lipid and surfactant portions on the resulted droplet size upon aqueous dilution. Formulations containing mixed glycerides showed enhanced self-emulsification with both lipophilic and hydrophilic surfactants. Increasing the polarity of the lipid portion in the formulation leaded to progressive water solubilization capacity. In addition, formulations containing medium chain mixed glycerides and hydrophilic surfactants showed lower droplet size compared with their long chain and lipophilic counterparts. The inclusion of mixed glycerides in the lipid formulations enormously enhances the formulation efficiency.

Novel self-nanoemulsifying drug delivery systems (SNEDDS) for oral delivery of cinnarizine: design, optimization, and in-vitro assessment.

Due to its extreme lipophilicity, the oral delivery of cinnarizine (CN) encounters several problems such as poor aqueous solubility and pH-dependent dissolution, which result in low and erratic bioavailability. The current study aims to design self-nanoemulsifying drug delivery systems (SNEDDS) of CN that circumvent such obstacles. Equilibrium solubility of CN was determined in a range of anhydrous and diluted lipid-based formulations. Dynamic dispersion tests were carried out to investigate the efficiency of drug release and magnitude of precipitation that could occur upon aqueous dilution. Droplet sizes of selected formulations, upon (1:1,000) aqueous dilution, were presented. The optimal formulations were enrolled in subsequent dissolution studies. The results showed that increasing lipid chain length and surfactant lipophilicity raised the formulation solvent capacity, while adding co-solvents provoked a negative influence. The inclusion of mixed glycerides and/or hydrophilic surfactants improved the drug release efficiency. Generally, no significant precipitation was observed upon aqueous dilution of the formulations. Five formulations were optimal in terms of their superior self-emulsifying efficiency, drug solubility, dispersion characteristics, and lower droplet size. Furthermore, the optimal formulations showed superior dissolution profile compared to the marketed (Stugeron®) tablet. Most importantly, they could resist the intensive precipitation observed with the marketed tablet upon shifting from acidic to alkaline media. However, SNEDDS containing medium-chain mixed glycerides showed the highest drug release rate and provide great potential to enhance the oral CN delivery. Accordingly, the lipid portion seems to be the most vital component in designing CN self-nanoemulsifying systems.

Enhanced Dissolution of Luteolin by Solid Dispersion Prepared by Different Methods: Physicochemical Characterization and Antioxidant Activity.

Luteolin (LT) is a poorly soluble bioactive compound that suffered bioavailability problems after oral administration. Hence, the aim of the proposed research work was to formulate and investigate various solid dispersions (SDs) of LT in order to enhance its dissolution and bioactivity. LT-SD was prepared using polyethylene glycol 4000 (PEG 4000) as a carrier at the mass ratios of 1:1, 1:2, and 1:4. LT-SD was prepared using different methods including fusion (FU), solvent evaporation (SE), and microwave irradiation (MI) methods. The prepared LT-SD was duly characterized in terms of differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), infrared (IR) spectroscopy, and nuclear magnetic resonance (NMR) and evaluated for dissolution and in vitro antioxidant activity. The results of DSC, XRD, SEM, IR, and NMR suggested the formation of LT-SD. After 90 min of the dissolution study, the results displayed that the % release of LT from prepared SD was significantly higher compared with the pure LT and its physical mixture dispersion (PMD). LT-SD prepared using the MI method displayed the maximum release of LT (i.e., 97.78 ± 4.41%) at a 1:2 mass ratio of LT:PEG 4000. The LT-SD prepared using the SE method displayed the maximum release of 93.78 ± 3.98% at a mass ratio of 1:4 of LT:PEG 4000. The SD prepared by the MI method showed enhanced dissolution due to higher aqueous solubility and the reduction of particle size. The solid-state characterization studies (DSC, XRD, SEM, IR, and NMR studies) suggested the morphological conversion of LT into the amorphous form from the crystalline state. The results of the antioxidant study revealed that the formation LT-SD displayed significantly higher radical scavenging activity than the pure LT. Therefore, SD obtained using PEG 4000 could be a potential strategy for maximizing the solubility, in vitro dissolution, and therapeutic efficacy of LT.

Simultaneous separation of antihyperlipidemic drugs by green ultrahigh-performance liquid chromatography-diode array detector method: Improving the health of liquid chromatography.

Statins in combination with fibrates show beneficial effects on the lipoprotein profile of patients because they have positive complimentary effects on lipid profile. A new green ultrahigh-performance liquid chromatography-diode array detector method for simultaneous analysis of simvastatin (SMV) and fenofibrate (FNF) in standard form, marketed formulations, and self-emulsifying drug delivery system formulations was developed and validated in the present investigation. The method utilized C18 as stationary phase and a combination of methanol:water (8:2) as an eluent. It was found that selected eluent provided short run time (2.5 minutes), better peak symmetry and satisfactory values of other chromatographic parameters such as resolution (Rs=2.325), capacity factor (k, 3.0 and 4.2 for SMV and FNF, respectively), selectivity (α =1.4), and number of theoretical plates (N, 4265 and 5285 for SMV and FNF, respectively). An excellent linear relationship (r2 0.998 and 0.997 for SMV and FNF, respectively) was observed for linear regression data for the calibration plots. The developed system was validated for accuracy, precision, robustness (˃ 2% for both drugs) and recovery (98-102% for both drugs). Results obtained from the statistical treatment of the values obtained for different parameters proved that the method is suitable, reproducible, and selective for the simultaneous analysis of SMV and FNF in bulk, marketed, and self-emulsifying drug delivery system formulations. The replacement of commonly applied toxic solvents with innocuous and environmentally benign solvents provides a better option than the more toxic processes in drug analysis.

GC-MS-based Metabolomic Profiling of Thymoquinone in Streptozotocin-induced Diabetic Nephropathy in Rats.

*Diabetic nephropathy is a common complication of diabetes mellitus and one of the major etiologies of end-stage renal disease. Specific therapeutic interventions are necessary to treat such complications. The present study was designed to investigate the metabolomic changes induced by thymoquinone for the treatment of diabetic nephropathy, using a rodent model. Rats were divided into three different groups (n = 6 each): control, diabetic, and thymoquinone- treated diabetic groups. Metabolites in serum samples were analyzed via gas chromatography-mass spectrometry. Multiple changes were observed, including those related to the metabolism of amino acids and fatty acids. The correlation analysis suggested that treatment with thymoquinone led to the reversal of diabetic nephropathy that was associated with modulations in the metabolism and proteolysis of amino acids, fatty acids, glycerol phospholipids, and organic acids. In addition, we explored the mechanisms linking the metabolic profiling of diabetic nephropathy, with a particular emphasis on the potential roles of increased reactive oxygen species production and mitochondrial dysfunctions. Our findings demonstrated that metabolomic profiling provided significant insights-into the basic mechanisms of diabetic nephropathy and the therapeutic effects of thymoquinone.

Influence of the microwave technology on solid dispersions of mefenamic acid and flufenamic acid.

The present studies were undertaken to develop solvent-free solid dispersions (SDs) for poorly soluble anti-inflammatory drugs mefenamic acid (MA) and flufenamic acid (FFA) in order to enhance their in vitro dissolution rate and in vivo anti-inflammatory effects. The SDs of MA and FFA were prepared using microwaves irradiation (MW) technique. Different carriers such as Pluronic F127® (PL), Eudragit EPO® (EPO), polyethylene glycol 4000 (PEG 4000) and Gelucire 50/13 (GLU) were used for the preparation of SDs. Prepared MW irradiated SDs were characterized physicochemically using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infra-red (FT-IR) spectroscopy, powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The physicochemical characteristics and drug release profile of SDs were compared with pure drugs. The results of DSC, TGA, FT-IR, PXRD and SEM showed that SDs were successfully prepared. In vitro dissolution rate of MA and FFA was remarkably enhanced by SDs in comparison with pure MA and FFA. The SDs of MA and FFA prepared using PEG 400 showed higher drug release profile in comparison with those prepared using PL, EPO or GLU. The dissolution efficiency for MA-PEG SD and FFA-PEG SD was obtained as 61.40 and 59.18%, respectively. Optimized SDs were also evaluated for in vivo anti-inflammatory effects in male Wistar rats. The results showed significant % inhibition by MA-PEG (87.74% after 4 h) and FFA-PEG SDs (81.76% after 4 h) in comparison with pure MA (68.09% after 4 h) and pure FFA (55.27% after 4 h) (P<0.05). These results suggested that MW irradiated SDs of MA and FFA could be successfully used for the enhancement of in vitro dissolution rate and in vivo therapeutic efficacy of both drugs.

Effects of Paeonia emodi on hepatic cytochrome P450 (CYP3A2 and CYP2C11) expression and pharmacokinetics of carbamazepine in rats.

Herbal medicines, dietary supplements, and other foods may pharmacokinetically and/or pharmacodynamically interact with carbamazepine (CBZ), which could lead to potential clinical consequences. Paeonia emodi (PE) is one of the herbs used as complementary therapy in the treatment of epileptic patients in some cultures, and may also be co-administered with CBZ. This study evaluates the effects of PE on the pharmacokinetics of CBZ and determines a possible mechanism of interaction. Rats were administered vehicle saline or PE (200mg/kg, p.o. daily for 7days), then administered a single CBZ dose (80mg/kg, p.o.) on day 7. Plasma samples were analyzed for CBZ concentrations using a sensitive reversed-phase high-performance liquid chromatography (RP-HPLC) assay. Pharmacokinetic parameters were calculated using non-compartmental analysis. The co-administration of PE with CBZ resulted in increased plasma maximum concentration (Cmax), area under the curve (AUC0-∞), and half-life (T½), by 14.61%, 48.12%, and 43.72%, respectively. The calculated oral clearance (CL/F) was reduced by 33.54%, while the volume of distribution (Vss) was unaffected. The PE extract also showed a significant potential to reduce CYP3A and CYP2C protein expression by approximately 50%. Therefore, a reduction in the metabolic capacity responsible for CBZ clearance appears to be the mechanism behind this herb-drug interaction. Consequently, the concomitant administration of PE and CBZ should be viewed cautiously. Further studies are needed to determine the clinical relevance of these observations.

Oral bioavailability enhancement and hepatoprotective effects of thymoquinone by self-nanoemulsifying drug delivery system.

Thymoquinone (TQ) is a poorly water soluble bioactive compound which shows poor oral bioavailability upon oral administration. Due to poor aqueous solubility and bioavailability of TQ, various self-nanoemulsifying drug delivery systems (SNEDDS) of TQ were developed and evaluated for enhancement of its hepatoprotective effects and oral bioavailability. Hepatoprotective and pharmacokinetic studies of TQ suspension and TQ-SNEDDS were carried out in rat models. Different SNEDDS formulations of TQ were developed and thermodynamically stable TQ-SNEDDS were characterized for physicochemical parameters and evaluated for drug release studies via dialysis membrane. Optimized SNEDDS formulation of TQ was selected for further evaluation of in vivo evaluation. In vivo hepatoprotective investigations showed significant hepatoprotective effects for optimized TQ-SNEDDS in comparison with TQ suspension. The oral administration of optimized SNEDDS showed significant improvement in in vivo absorption of TQ in comparison with TQ suspension. The relatively bioavailability of TQ was enhanced 3.87-fold by optimized SNEDDS in comparison with TQ suspension. The results of this research work indicated the potential of SNEDDS in enhancing relative bioavailability and therapeutic effects of natural bioactive compounds such as TQ.

Development of self-nanoemulsifying drug delivery systems for the enhancement of solubility and oral bioavailability of fenofibrate, a poorly water-soluble drug.

BACKGROUND: Self-nanoemulsifying drug delivery systems (SNEDDS) have become a popular formulation option as nanocarriers for poorly water-soluble drugs. The objective of this study was to investigate the factor that can influence the design of successful lipid formulation classification system (LFCS) Type III SNEDDS formulation and improve the oral bioavailability (BA) of fenofibrate. MATERIALS AND METHODS: LFCS Type III SNEDDS were designed using various oils, water-soluble surfactants, and/or cosolvents (in considering the polarity of the lipids) for the model anticholesterol drug, fenofibrate. The developed SNEDDS were assessed visually and by measurement of the droplet size. Equilibrium solubility of fenofibrate in the SNEDDS was conducted to find out the maximum drug loading. Dynamic dispersion studies were carried out (1/100 dilution) in water to investigate how much drug stays in solution after aqueous dispersion of the formulation. The BA of SNEDDS formulation was evaluated in the rat. RESULTS: The results from the characterization and solubility studies showed that formulations containing mixed glycerides were highly efficient SNEDDS as they had higher solubility of the drug and produced nanosized droplets. The dispersion studies confirmed that SNEDDS (containing polar mixed glycerides) can retain >98% drug in solution for >24 hours in aqueous media. The in vivo pharmacokinetics parameters of SNEDDS formulation in comparison with pure drug showed significant increase in C max and AUC0- t , ~78% and 67%, respectively. The oral BA of fenofibrate from SNEDDS in rats was ~1.7-fold enhanced as compared with the BA from pure drug. CONCLUSION: Fenofibrate-loaded LFCS Type III SNEDDS formulations could be a potential oral pharmaceutical product for administering the poorly water-soluble drug, fenofibrate, with an enhanced oral BA.

Momordica charantia polysaccharides mitigate the progression of STZ induced diabetic nephropathy in rats.

Diabetic nephropathy (DN) has become a primary cause of end-stage kidney disease. Several complex dynamics converge together to accelerate the advancement of DN. The present investigation was postulated to explore the mechanism of reno-protective nature of Momordica Charantia polysaccharides (MCP) by evaluating the anti-hyperglycemic, anti-lipidemic as well as markers for oxidative stress and antioxidant proficiency in streptozotocin (STZ)-induced diabetic rats. The oral administration of MCP showed a significant normalization in the levels of kidney function test in the STZ-induced diabetic rats. The levels of blood urea nitrogen (BUN), urea protein and creatinine increased by 316.58%, 195.14% and 800.97% respectively, in STZ-induced diabetic rats when compared with normal rats. MCP treatment also illustrated a significant improvement in glutathione peroxidase, superoxide dismutase and catalase levels, with a significant decline in MDA in diabetic kidneys. Immunoblots of heme-oxygenase 1 (HO-1) and Nrf2 of MCP treated diabetic rats showed a significant up-regulation of HO-1 and Nrf2 protein. Histological and ultra-structural observations also reveal that MCP efficiently protects the kidneys from hyperglycemia-mediated oxidative damage. These findings illustrate that the reno-protective nature of MCP mitigates the progression of STZ induced DN in rats by suppression of oxidative stress and amelioration of the HO-1/Nrf2 pathway.

Antioxidant Potential and In Situ Analysis of Major and Trace Element Determination of Ood-saleeb, a Known Unani Herbal Medicine by ICP-MS.

The intention of the present research work was to investigate the antioxidant activity and trace element analysis of Ood-saleeb, a known herbal medicine. Preliminary screening of phytochemicals showed that the extract of Ood-saleeb had flavonoids and phenolics. The significant activities in all antioxidant assays were observed in the extract of Ood-saleeb in comparison with the standard antioxidant with respect to dose of Ood-saleeb. Incredible activities to scavenge reactive oxygen species were also observed by the extract of Ood-saleeb. The IC50 values of all factors were determined using ascorbic acid as a standard. The inductive coupled plasma-mass spectroscopy (ICP-MS) was employed for the estimation of trace elements in Ood-saleeb extract. The concentrations of up to 18 elements were detected successfully. Silicon was found in high concentration (85.3 µg/g) while lithium was in low concentration (3 ng/g). The trace elements in the sample were found at different percentage levels which play a key role in the treatment of diseases.

Sinapic acid mitigates gentamicin-induced nephrotoxicity and associated oxidative/nitrosative stress, apoptosis, and inflammation in rats.

AIMS: In this study, the renoprotective functions of sinapic acid (SA), a polyphenol, on gentamicin-induced nephrotoxicity and the pathway that mediates this function were examined. MAIN METHODS: Kidney function markers (serum urea, uric acid, creatinine, LDH, and γ-GGT) and histopathological examinations of the kidney were used to evaluate gentamicin-induced nephrotoxicity. Oxidative stress markers (lipid peroxidation and total protein), renal nitrosative stress (nitric oxide), antioxidant enzymes (catalase and NP-SH), inflammation markers (NF-κB [p65], TNF-α, IL-6, and myeloperoxidase [MPO]), and apoptotic markers (caspase 3, Bax, and Bcl-2) were also assessed. KEY FINDINGS: SA (10 and 20mg/kg) pretreatment along with gentamicin restored kidney function, upregulated antioxidant levels, and downregulated lipid peroxidation and nitric oxide levels, resulting in significant decreases in oxidative and nitrosative stress. Gentamicin promoted the upregulation of renal cytokines (TNF-α and IL-6), nuclear NF-κB (p65) expression, NF-κB-DNA binding activity, and MPO activity were significantly down regulated upon SA pretreatment. Furthermore, SA pretreatment downregulated caspase 3 and Bax protein expressions and upregulated Bcl-2 protein expression. SA pretreatment also mitigated the magnitude of histological damage and reduced neutrophil infiltration in renal tubules. SIGNIFICANCE: These outcomes indicated that SA pretreatment mitigates renal impairment and structural injuries via the downregulation of oxidative/nitrosative stress, inflammation, and apoptosis in the kidney.

Dissolution improvement of solid self-emulsifying drug delivery systems of fenofibrate using an inorganic high surface adsorption material.

Solidification of lipid formulations using adsorbents is a recent technique attracting great interest due to its favourable properties including flexibility in dose division, reduction of intra-subject and inter-subject variability, improvement in efficacy/safety profile and enhancement of physical/ chemical stability. The current study aims to convert liquid self-emulsifying/nanoemulsifying drug delivery systems (SEDDS/SNEDDS) into solid SEDDS/SNEDDS and to assess how adsorption of the drug onto an inorganic high surface area material, NeusilinR grade US2 (NUS2), affects its in vitro dissolution performance. Lipid formulation classification systems (LFCS) Type III formulations were designed for the model anti-cholesterol drug fenofibrate. NUS2 was used to solidify the SEDDS/SNEDDS. Particle size and SEM analyses of solid SEDDS/SNEDDS powder were carried out to investigate the adsorption efficiency. In vitro dissolution studies were conducted to compare the developed formulations with the marketed product. The results of characterization studies showed that the use of 50% (m/m) adsorbent resulted in superior flowability and kept the drug stable is amorphous state. Dissolution studies allow the conclusion that the formulation containing a surfactant of higher water solubility (particularly, Type IIIB SNEDDS) has comparably faster and higher release profiles than Type IIIA (SEDDS) and marketed product.