Bulletin of Faculty of Pharmacy, Cairo University最新文献

Two simple and sensitive visible spectrophotometric methods (A and B) were developed for the determination of alogliptin in bulk and in its tablet dosage forms. The methods use the reaction of alogliptin with picric acid (method A) or 2,4 dinitrophenol (method B) in the chloroform medium. The complex of alogliptin with picric acid (method A) or 2,4 dinitrophenol (method B) showed λ_max at 415 nm and 430 nm respectively. The different conditions affecting the formation and stability of the complexes were optimized. The methods were validated statistically according to ICH. The calibration curve is linear over the concentration range of 10–60 μg ml⁻¹ and 10–50 μg ml⁻¹ for methods A and B, respectively. The proposed methods were successfully applied for the assay of alogliptin in tablets with good recoveries. Interference was not observed from common tablet excipients.

The interactions of poorly aqueous soluble endothelin receptor antagonist bosentan (BOS) with hydroxypropyl-β-cyclodextrin (HPβCD) were assessed in presence and absence of an amino acid l-arginine (ARG), to improve its physicochemical properties. Initially, the phase solubility studies conducted in distilled water followed by thermodynamic investigations demonstrated an A_L type of solubility profile and an enthalpy driven exothermic complexation process, respectively, in all cases. The analytical evidences for the formation of lyophilized binary and ternary complexes in solid state were generated and confirmed by differential scanning calorimetry (DSC), Fourier transformation infrared spectroscopy (FTIR), X-ray powder diffractometry (XPRD) and scanning electron microscopy (SEM). The solubility and dissolution of binary and ternary complexes were significantly improved upon complexation as compared to BOS alone, supported by decreased log P values of the complexes. However, the complexation efficiency of ternary system was found to be higher than binary, justifying the addition of ARG as an auxiliary substance to reduce the workable amount of HPβCD during formulation.

Two chromatographic methods have been established and validated for simultaneous determination of mixture of Dimenhydrinate (DMH) and Cinnarizine (CIN) in their pharmaceutical formulation and in presence of Cinnarizine impurity (1-(Diphenylmethyl) piperazine); CIN impurity. The first method was TLC-densitometric one, depends on separation and quantitation of DMH, CIN and CIN impurity on TLC silica gel 60 F₂₅₄ plates, using chloroform:methanol:glacial acetic acid:ammonia solution (9.5:0.5:0.1:0.1, by volume) as a developing system followed by densitometric measurement at 235 nm. Linear relationships were obtained in the range of 0.2–2, 0.4–1.6 and 0.1–1 μg/band for DMH, CIN and CIN impurity, respectively. The studied components were well resolved from each other with significantly different R_f values of 0.35, 0.52 and 0.04 for DMH, CIN and CIN impurity, respectively. The second method was RP-HPLC, separation on C8 column using 0.05 M KH₂PO₄ (pH = 3):methanol (35:65, v/v) as the mobile phase at a flow rate of 1 mL/min and DAD detection at 240 nm. Linear relationships were obtained in the ranges of 3–30, 2–20 and 1–10 μg/mL, with significantly different R_t values of 3.27, 6.95 and 2.87 min for DMH, CIN and CIN impurity, respectively. The developed methods were validated according to ICH guidelines demonstrating good accuracy and precision. The results were statistically compared with those obtained by reported HPLC method and no significant difference was obtained.

Atopic dermatitis (AD) is the most prevalent chronic disease that affects the skin and is featured by inflammation of the skin. Treatment of AD is entirely focused on to limit the itching, skin repairing as well as reducing the inflammation whenever required. A number of therapeutic agents are available for the treatment of AD. However, topical delivery to the skin has been a consistent challenge for researchers, because of the barrier nature of skin. The present review explores the novel nano-sized formulations of various actives researched for AD therapy via topical route. Feasibility of various nano-carrier systems such as elastic vesicles, nanoemulsions, lipid nanoparticles, polymeric micelles and dendritic nanoparticles has been elaborated. The write up traces the pre-clinical and clinical aspects of the nano-formulations. Nano-formulations are found to be an emerging modality for the treatment of AD as they offer targeted delivery, better penetration, enhanced therapeutic efficacy and decreased systemic side effects.

Neuropathy is the least understood and most devastating complication associated with diabetes. Diabetic neuropathy develops in patients despite of regular therapy, indicating that marketed drugs has minimal effect on pathways leading to the development and progression of these complications. Present study was aimed to evaluate natural compounds for their ability to interfere with pathways leading to the development of diabetes mediated neurological complications and compare their efficacy with marketed anti-diabetic drugs. Anti-diabetic potential of ascorbic acid, gallic acid, quercetin, ellagic acid, cinnamic acid, caffeine and piperine was predicted by evaluating in-silico interaction energy (kcal/mol) of these compounds with insulin receptor, peroxisome proliferator-activated receptor gamma-γ and dipeptidyl peptidase-4 proteins. Ascorbic acid, gallic acid, quercetin and ellagic acid showed excellent in-vitro antioxidant activity in DPPH radical scavenging and inhibition of lipid peroxidation assay, which was 1.5–3 folds better than the marketed drugs. Quercetin, gallic acid, cinnamic acid, piperine and caffeine efficiently prevented H₂O₂ induced genotoxicity, which commercial drugs failed to prevent. Further, quercetin, ellagic acid, caffeine and ascorbic acid were 3–4.7 folds better than marketed drugs in inhibiting α-amylase activity. Herbal molecules and rosiglitazone showed comparable results for glucose uptake, which may be attributed to enhanced GLUT4 translocation into primary neuronal culture under hyperglycemic conditions. In conclusion, currently available marketed anti-diabetic drugs have minimal effect on the pathways leading to diabetic neuropathy and supplementing diabetic therapeutics with quercetin, ascorbic acid, caffeine and ellagic acid may be better suited to counter diabetic neuropathy through inhibiting oxidative stress, genotoxicity and improving neuronal glucose utilization.

Pyrrolidine dithiocarbamate (PDTC), a low-molecular-weight thiol antioxidant, possesses neuroprotection; however, its possible modulatory effect in Parkinson’s disease (PD) has not been tested. Male Wistar rats were injected with rotenone to induce PD-like symptoms. Histopathological findings showed that striatal neurons were degenerated following rotenone administration, an effect that was accompanied by behavioral deficits. Furthermore, rotenone decreased striatal dopamine (DA) and glutamate and prominently increased serotonin, GABA, glutathione (GSH), thiobarbituric acid reactive substances (TBARS), and myeloperoxidase (MPO) levels. Daily treatment with PDTC protected against rotenone induced changes at the microscopic level, decreased the extent of motor dysfunctions, and markedly increased DA and suppressed glutamate levels. It also reduced TBARS, GSH, and MPO. Whereas, rotenone neither affected striatal caspase-3 activity nor tumor necrosis factor-α level, PDTC treatment reduced the later. The current study reveals the effectiveness of PDTC against rotenone-induced PD via enhancement of DA, as well as antioxidant and anti-inflammatory properties.

Voriconazole is second-generation triazole used for the treatment of fungal infections but has serious unwanted adverse effects, which could be reduced by topical semisolid dosage form. Major drawbacks of topical semisolid products are poor patient compliance, cross contamination; gels are easily rubbed off by clothing and during day-to-day activities, physical instability. The purpose of the present work was to fabricate 0.5% w/w voriconazole transdermal spray for fungal infection. The transdermal spray was generated by using a film forming polymers like Eudragit RLPO and ethyl cellulose (1:2 ratios) along with eutectic camphor: menthol (1:1) mixture used as a penetration enhancer. The formulation optimized by constrained 3² factorial design. Regression analysis and response surface methodology were used to optimize the effect of polymers and formulate checkpoint batch based on overlay plots. The transdermal spray was subjected to evaluate parameters related to formulation and containers. The concentration of Eudragit RLPO and ethyl cellulose was showed influence on viscosity as well as t₅₀. Diffusion study was showed 75% of voriconazole transport with 65.8 μgcm⁻² h⁻¹ fluxes. Penetration enhancers’ had shown an increase in 1.68 fold of the penetration of voriconazole through the formulation. The study was concluded that fabricated film forming voriconazole transdermal spray formulations penetrate to the deep layer of the skin and was feasible to treat the dermatological fungal infection. This delivery platform is opened a wide range of treatment of fungal infection as compared to conventional formulations.

The purpose of this study was to investigate the effect of polymer and surfactant concentration on drug loading and in vitro drug release of micro particulate drug delivery system of Losartan potassium (LST). Microparticles were prepared by O/O solvent emulsification method. A 3² full factorial design was used to derive statistical equation and construct contour plots to predict responses. The independent variables selected were polymer concentration (A), surfactant concentration (B). Dependent variables were percentage drug loading (Y1) and percentage drug release at 12 h (Y2). The in vitro drug release profile of prepared microparticles was compared with marketed tablet formulation. The release profile of microparticles was found to be sustained as compared to the marketed formulation. The drug loading was found to be in the range of 15.32% (F6) to 22.27% (F5). FT-IR analysis revealed no drug excipient interference. The morphology of evaluated microparticles at −1 level was found to be spherical and smooth in nature while at higher level +1 it was found to be rough, irregular, with erosion, cracks and wrinkles on the surface. In XRD analysis crystalline pattern of pure LST was changed to amorphous pattern when converted to microparticles.

In this search, three selective spectrophotometric and TLC-densitometric methods have been developed and validated for quantitative determination of Pyrazinamide (PYN) and its impurity, Pyrazine-2-carboxylic acid (PYA). The proposed methods are third derivative spectrophotometric (Method I), first derivative of ratio spectra spectrophotometric (Method II), mean centering of ratio spectra spectrophotometric (MCR) (Method III) and TLC-densitometric (Method IV). In method (I); ³D amplitudes at 276.2 and 274.6 nm were measured and used for determination of PYN and PYA, respectively. In method (II); PYN was determined by measuring the ¹DD peak amplitude at 225.8 nm using 30 µg mL⁻¹ of PYA as a divisor; on the other hand PYA was determined by measuring this amplitude at 245.2 nm using 18 µg mL⁻¹ of PYN as a divisor. For method (III); the amplitudes of the mean centered ratio spectra at 268.4 and 268.8 nm were used for PYN and PYA, respectively. On the other hand, the forth method is TLC-densitometric method at which the chromatographic separation was achieved using silica gel 60 F₂₅₄ TLC plates and mixture of methylene chloride: methanol: ammonia solution (7:3:0.1, by volume) as a developing system followed by UV-scanning at 275 nm.

The proposed methods were successfully applied for determination of the PYN in its pharmaceutical formulation. Also they were statistically compared with the reported method using student’s-t and F-tests and there was no significant difference between them regarding both accuracy and precision.

Objectives

This study was done to estimate the potential neuroprotective role of potassium channel openers in cerebral ischemia–reperfusion (IR) injury in streptozotocin (STZ) induced type-I diabetic rats (T1DR).

Methods

Potassium channel openers – cromakalim, cinnarizine and nicorandil; potassium channel blocker –glibenclamide, insulin (as an antidiabetic standard), telmisartan (as an anti-hypertensive standard agent) and vitamin E (as an antioxidant and antiapoptotic standard agent) were given for 3 days in streptozotocin (45 mg/kg i.v.) induced type I diabetic rats along with middle cerebral artery occlusion. After 24 h of surgery, plasma glucose, neurobehavioral score, cerebral infarct volume, blood pressure and caspase-3 levels were measured to evaluate the mechanism of potassium channel openers (KCOs) for neuroprotection.

Results

Following STZ administration and ischemia–reperfusion, blood sugar, neurobehavioral score, cerebral infarct volume and caspase-3 levels were significantly high in diabetic-IR groups. Treatment with cromakalim, cinnarizine, nicorandil, insulin and vitamin E significantly reduce neurobehavioral score while nicorandil and vitamin E significantly reduced cerebral infarct volume. Caspase-3 levels were significantly reduced by cromakalim and nicorandil treated animals. Except insulin and glibenclamide, none of the agents significantly reduce plasma glucose levels.

Conclusion

Treatment of ischemic stroke with potassium channel openers in T1DR is neuroprotective. Inhibition of apoptosis may contribute to their neuroprotective effects after stroke in T1DR.