Selective detection of azelnidipine in pharmaceuticals via carbon dot mediated spectrofluorimetric method: A green approach.

A spectrofluorimetric method using fluorescent carbon dots (CDs) was developed for the selective detection of azelnidipine (AZEL) pharmaceutical in the presence of other drugs. In this study, N-doped CDs (N-CDs) were synthesized through a single-step hydrothermal process, using citric acid and urea as precursor materials. The prepared N-CDs showed a highly intense blue fluorescence emission at 447 nm, with a photoluminescence quantum yield of ~21.15% and a fluorescence lifetime of 0.47 ns. The N-CDs showed selective fluorescence quenching in the presence of all three antihypertensive drugs, which was used as a successful detection platform for the analysis of AZEL. The photophysical properties, UV-vis light absorbance, fluorescence emission, and lifetime measurements support the interaction between N-CDs and AZEL, leading to fluorescence quenching of N-CDs as a result of ground-state complex formation followed by a static fluorescence quenching phenomenon. The detection platform showed linearity in the range 10-200 µg/ml (R2 = 0.9837). The developed method was effectively utilized for the quantitative analysis of AZEL in commercially available pharmaceutical tablets, yielding results that closely align with those obtained from the standard method (UV spectroscopy). With a score of 0.76 on the 'Analytical GREEnness (AGREE)' scale, the developed analytical method, incorporating 12 distinct green analytical chemistry components, stands out as an important technique for estimating AZEL.

Stability-Indicating HPTLC Method for Simultaneous Estimation of Flurbiprofen and Chloramphenicol in Ophthalmic Solution.

A specific, accurate and reproducible stability-indicating high performance thin layer chromatography (HPTLC) method was developed for the estimation of flurbiprofen and chloramphenicol in the presence of their degradation products. Degradation studies of both the drugs were carried out in acidic, alkaline, neutral, oxidative, photolytic and thermal stress conditions. Separation was performed on thin layer chromatography plate precoated with silica gel 60 F254 using ethyl acetate : n-hexane : methanol : tri-ethyl amine (5 : 4 : 2 : 0.5, v/v/v/v). Spots at retention factor 0.29 and 0.62 were recognized as flurbiprofen and chloramphenicol, respectively, and were quantified through densitometric measurements at wavelength 267 nm. Method was found to be linear over the concentration range 12-60 ng/spot with correlation coefficient of 0.9997 for flurbiprofen and 200-1,000 ng/spot with correlation coefficient of 0.9977 for chloramphenicol. The proposed method was applied to the estimation of flurbiprofen and chloramphenicol in commercial ophthalmic formulation. The developed HPTLC method can be applied for routine analysis of flurbiprofen and chloramphenicol in the presence of their degradation products in their individual as well as combined pharmaceutical formulations.

Development of controlled release osmotic pump tablet of glipizide solid dispersion.

PURPOSE: To develop controlled release osmotic pump tablets (COPT) of glipizide (GZ) solid dispersion (SD). METHODS: In elementary osmotic pump (EOP) tablets, an osmotic core with the drug is surrounded by a semi-permeable membrane which is drilled with a delivery orifice. COPT tablets eliminate the need of drilling process as controlled release can be achieved by the presence of osmogen in the coating. Poorly water soluble drug molecule cannot give satisfactory drug release hence GZ solid dispersion was prepared in the present study. The SDs having different ratio of drug to Poloxamer (PXM) 188 were prepared by hot melt method and optimized by solubility study, drug content estimation and in vitro dissolution study. Effect of two independent variables, amount of osmogen (potassium chloride) and hydrophilic polymer (polyethylene oxide WSR 303), were investigated using 3(2) factorial design. Core and coated tablets were evaluated for pharmacotechnical parameters. In-vitro drug release profiles of COPT tablets were compared with marketed with push-pull osmotic pump tablet, Glucotrol XL. RESULTS: Prepared core and coated tablets showed acceptable pharmacotechnical parameters. Drug release was directly proportional to initial level of hydrophilic polymer, but inversely related to the osmogen, confirming osmotic mechanism. Zero order drug release pattern was achieved which was comparable to marketed product. CONCLUSION: Novel oral controlled release of glipizide was successfully achieved by incorporating glipizide solid dispersion into osmotic system.

Effect of Boerhaavia diffusa in experimental prostatic hyperplasia in rats.

OBJECTIVE: Present investigation was undertaken to study the effectiveness of hydroalcoholic extract of roots of Boerhaavia diffusa in experimental benign prostatic hyperplasia (BPH) in rats using various animal models. MATERIALS AND METHODS: BPH in rats was induced by subcutaneous injection of testosterone (5 mg/kg) daily for 28 days. Rats were divided in to five groups (six rats each). A negative control group received arachis oil (1 ml/kg s.c.) and four groups were injected testosterone. These four groups were further divided into reference group (finasteride 1 mg/kg), model group (testosterone), study group A (B. diffusa 100 mg/kg), and study group B (B. diffusa 250 mg/kg). On the 29(th) day, rats were sacrificed and body weight, prostate weight, bladder weight, and serum testosterone level were measured and histological studies were carried out. Further in vitro analysis of B. diffusa extract on contractility of isolated rat vas deferens and prostate gland, produced by exogenously administered agonists were carried out. All results were expressed as mean ± SEM. 0 Data were analyzed by one-way analysis of variance followed by Tukey's test. RESULTS: B. diffusa (100 mg/kg) treatment for 28 days resulted in significant inhibition of prostate growth (P < 0.05). Drug extract did not have significant change on serum testosterone level. Histopathological analysis of prostate gland supported above results. Results of in vitro experiment suggest that extracts had attenuated the contractile responses of isolated vas deferens and prostate gland to exogenously applied agonists. CONCLUSION: The results suggested that treatment with B. diffusa may improve symptoms of disease and inhibit the increased prostate size. In vitro study implies that herbal extracts has the machinery to produce beneficial effect on prostatic smooth muscle, which would relieve the urinary symptoms of disease. B. diffusa could be a potential source of new treatment of prostatic hyperplasia.

Formulation and optimization of ethosomes for transdermal delivery of ropinirole hydrochloride.

The present study focuses on the formulation of ethosomal gel of ropinirole hydrochloride (ropinirole HCl), an anti-Parkinsonian drug, for delivery as a carrier for transdermal application. The ethosomes were prepared using different concentrations of phospholipids (2-5 % w/v), ethanol (20-50 % w/v), ropinirole HCl (5 % w/v) and water. They were optimized using 3(2) full factorial designs to study the effect of independent variables, concentrations of ethanol and lecithin on dependent variables, entrapment efficiency and in-vitro drug release at 24 hrs. The drug release profile exhibited Higuchi's and zero order kinetics. From the regression analysis, it was observed that independent variables had significant effect on response variables. Formulations were optimized using contour plot and response surface plot. The optimized formulation was found to be RS10 containing 30 % w/v ethanol and 4% w/v lecithin. The optimized formulation was evaluated for assay, particle characteristics, zeta potential, skin retention and stability. Ethosomal gel was prepared by incorporation of optimized ethosomal suspension into gel base. The ethosomal gel was characterized for physical appearance, pH, content uniformity, rheological behaviour, skin-retention, in-vitro and in-vivo drug release and stability. From the results it can fairly be concluded that ethosomes are capable of delivering ropinirole hydrochloride into systemic circulation by transdermal route. The amounts thus delivered are also equitable to those delivered orally and are delivered at a rate slow enough to achieve longer blood levels.

Design and evaluation of herbal hepatoprotective formulation against paracetamol induced liver toxicity.

AIM: To isolate and identify the quercetin from polyherbal hepatoprotective formulation. Polyherbal formulations were developed by using five bioactive fractionated extracts of Butea monosperma, Bauhinia variegata and Ocimum gratissimum for treatment of liver disorders by exploiting the knowledge of traditional system of medicine and evaluated for hepatoprotective activity using acute liver toxicity model of paracetamol induced liver damage in rats. METHODS: Major active fractions were isolated by solvent fractionation and quantified by HPTLC method. Two polyherbal tablet formulations were developed by the wet granulation method using microcrystalline cellulose, aerosil and other excipients and subjected for physicochemical evaluation to assess physical stability followed by pharmacological screening. The prepared tablets were finally subjected to stability testing to assess its shelf-life. The rats were monitored for change in liver morphology, biochemical parameters like serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP) and total bilirubin for polyherbal tablet formulation at 50 mg/kg and polyherbal tablet formulation at 100 mg/kg. RESULTS: Active principle was isolated, quantified by HPTLC and characterized with IR. Both formulations showed significant hepatoprotective activity. The histological studies were also support the biochemical parameters. From the results of biochemical analysis and histopathological studies, it can be accomplished that polyherbal tablet formulation at 100 mg/kg can be effectively formulated into a suitable dosage form with added benefit of no side effects for control and cure of chronic ailments like liver disorders. A comparative histopathological study of liver exhibited almost normal architecture as compared to toxicant group. CONCLUSION: Biochemical marker showed improved results for polyherbal tablet formulation at 100 mg/kg. Polyherbal tablet formulation contains a potent hepatoprotective agent suggested to be a flavone concentrated in polyherbal formulation which may find clinical application in amelioration of paracetamol induced liver damage.

Antiurolithiatic activity of saponin rich fraction from the fruits of Solanum xanthocarpum Schrad. & Wendl. (Solanaceae) against ethylene glycol induced urolithiasis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: A well-known traditional herb Solanum xanthocarpum is widely used in India for the management of different ailments including urolithiasis. This study was designed to rationalize the use of Solanum xanthocarpum in kidney stone and to investigate its mechanism of action. MATERIALS AND METHODS: The saponin rich fraction prepared from fruits of Solanum xanthocarpum (SXS) was evaluated for antiurolithiatic activity by in vitro and in vivo studies. In ethylene glycol (EG, 0.75% in drinking water for 28 days) induced urolithiasis model, two different experimental doses (20 mg/kg and 40 mg/kg, p.o., for 28 days) of saponin rich fraction were selected by dose fixation study. After 28 days, various biochemical parameters were measured in urine, serum and kidney homogenate. Kidneys were also subjected to histopathological analysis. RESULTS: In vitro calcium oxalate crystal (CaOx) nucleation as well as aggregation was inhibited in artificial urine solution by SXS. The lithogenic treatment caused polyuria, damage renal function and oxidative stress, manifested as increased malondialdehyde, depleted reduced glutathione and decreased antioxidant enzyme catalase activities of the kidneys, which were prevented by simultaneous administration with SXS. Lithogenic treatment also caused crystalluria, hyperoxaluria, hypercalciuria, hypocitrauria, and hypomagnesaemia. Deposition of CaOx in renal tissue and cellular injury were seen in histopathology. Co-administration of SXS had potential to prevent these pathological changes due to lithogenic treatment. Moreover, SXS raised level of glycosaminoglycan, a stone inhibitor macromolecule found in urine which decreased. CONCLUSION: The antiurolithiatic activity in Solanum xanthocarpum is mediated possibly through the inhibition of CaOx crystal formation and its effect on the urinary concentration of stone-forming constituents and nephrolithiasis inducing factors and this study rationalizes its medicinal use in urolithiasis.

Formulation and in vivo hypoglycemic effect of glipizide solid dispersion.

The present study was carried out with a view to enhance dissolution rate of poorly water-soluble drug glipizide (GZ) (BCS class II) using polyethylene glycol (PEG) 6000, PEG 8000 and poloxamer (PXM) 188 as carriers. Solid dispersions (SDs) were prepared by melting method using different ratios of glipizide to carriers. Phase solubility study was conducted to evaluate the effect of carrier on aqueous solubility of glipizide. SD was optimized by drug content estimation and in vitro dissolution study and optimised SD was subjected to bulk characterization, Scanning electron microscopy (SEM), Fourier transformation infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and X-ray diffraction study (XRD). Preclinical study was performed in mice to study the decrease in blood glucose level from prepared SD compared with pure drug. Due to high solubility and drug release, PXM 188 in weight ratio of 1:2 was optimized. Decrease in blood glucose level in mice from SD was significantly higher (p < 0.05) compared to pure glipizide. Thus, solid dispersion technique can be successfully used for the improvement of the dissolution profile of GZ.

Protective effect of aqueous extract of Oroxylum indicum Linn. (root bark) against DNBS-induced colitis in rats.

OBJECTIVE: Aqueous root extract of Oroxylum indicum was evaluated in rats against dinitrobenzene sulfonic acid (DNBS) induced colitis. MATERIALS AND METHODS: Rats were pre-treated orally for seven days and continued for four days after the induction of colitis with OI(aq) (100, 200, and 400 mg/kg) or vehicle. Colitis was induced by intracolonic instillation of 25 mg of DNBS per rat dissolved in 50% alcohol and 4 days later, the colonic mucosal damage was analyzed along with food intake, body weight, colon weight, spleen weight, histological damage, myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, reduced glutathione (GSH), and nitric oxide levels in colonic tissue homogenate. RESULTS: Significant reduction in gross damage area, weight loss and increase in colonic and spleen weight were evident in test substance-pretreated animals' dose dependently as compared to vehicle treated control. These effects were confirmed biochemically by a reduction in colonic myeloperoxidase activity, malondialdehyde levels, nitric oxide levels, and increase in reduced glutathione (GSH) levels. Furthermore, microscopic examination revealed diminution of inflammatory cell infiltration and submucosal edema in colon segments of rats treated with OI(aq). CONCLUSION: The results demonstrate the protective effect of OI(aq) in the animal model of acute colitis possibly through an antioxidant, anti-lipoperoxidative or due to reduction in nitric oxide generation.

Determination of gatifloxacin and ornidazole in tablet dosage forms by high-performance thin-layer chromatography.

A simple and sensitive high-performance thin-layer chromatography (HPTLC) method has been developed for the quantitative estimation of gatifloxacin and ornidazole in its combined dosage forms. Gatifloxacin and ornidazole were chromatographed on silica Gel 60 F(254) TLC plate using n-butanol:methanol:ammonia (6 M) (8:1:1.5 v/v) as the mobile phase and scanned at 302 nm using a Camag TLC Scanner 3. The R(f) value of gatifloxacin and ornidazole was found to be 0.21 +/- 0.02 and 0.76 +/- 0.04, respectively. The linearity of gatifloxacin and ornidazole were in the range of 100 - 500 ng/spot and 250 - 1250 ng/spot, respectively. The limit of detection was found to be 40 ng/spot for gatifloxacin and 100 ng/spot for ornidazole. The proposed method was applied for the determination of gatifloxacin and ornidazole in combined dosage forms.