Glaucoma is a common progressive eye disorder and the treatment strategies will benefit from nanoparticulate delivery systems with high drug loading and sustained delivery of intraocular pressure lowering agents. Niosomes have been reported as a novel approach to improve drug low corneal penetration and bioavailability characteristics. Along with this, poor entrapment efficiency of hydrophilic drug in niosomal formulation remains as a major formulation challenge. Taking this perspective into consideration, DORZOLAMIDE niosomes were prepared employing two different loading methodologies (passive and remote loading methods) and the effects of various formulation variables (lipid to drug ratio, cholesterol percentage, drug concentration, freeze/thaw cycles, TPGS content, and external and internal buffer molarity and pH) on encapsulation efficiency were assessed. Encapsulation of DORZOLAMIDE within niosomes increased remarkably by the incorporation of higher cholesterol percentage as well as increasing the total lipid concentration. Remote loading method showed higher efficacy for drug entrapment compared to passive loading technique. Incorporation of TPGS in bilayer led to decrease in EE; however, retarded drug release rate. Scanning electron microscopy (SEM) studies confirmed homogeneous particle distribution, and spherical shape with smooth surface. In conclusion, the highest encapsulation can be obtained using phosphate gradient method and 50% cholesterol in Span 60 niosomal formulation.

Objectives: Evaluation of the effectiveness and safety of sublingual timolol 0.5% and DORZOLAMIDE 2%. Methods: A randomized, double-masked, placebo controlled study of 120 normal human subjects was carried out in Ghaem Hospital - Mashhad. Volunteers were randomized to receive a single drop of either timolol, DORZOLAMIDE or placebo sublingually and IOP measurement were obtained before, 1 hour, and 2 hours after instillation of the drug.Results: The IOP was reduced by a mean of 3.97± 2.07mmHg (21.34%) 2 hours after sublingual timolol instillation (P<0.001). Sublingual DORZOLAMIDE and placebo had no ocular hypotensive effect. Conclusion: Sublingual timolol is an effective agent in lowering IOP and maybe an alternative to topical medication in glaucoma. This method of administration in glaucoma needs further study.

Purpose: Thermal analysis (TGA, DTG and DTA) and differential scanning calorimetry (DSC) have been used to study the thermal behavior of terazosin HYDROCHLORIDE (TER). Methods: Thermogravimetric analysis (TGA/DTG), differential thermal analysis (DTA) and differential scanning calorimetry (DSC) were used to determine the thermal behavior and purity of the used drug. Thermodynamic parameters such as activation energy (E*), enthalpy (DH*), entropy (DS*) and Gibbs free energy change of the decomposition (DG*) were calculated using different kinetic models.Results: The purity of the used drug was determined by differential scanning calorimetry (99.97%) and specialized official method (99.85%) indicating to satisfactory values of the degree of purity. Thermal analysis technique gave satisfactory results to obtain quality control parameters such as melting point (273oC), water content (7.49%) and ash content (zero) in comparison to what were obtained using official method: (272oC), (8.0%) and (0.02%) for melting point, water content and ash content, respectively.Conclusion: Thermal analysis justifies its application in quality control of pharmaceutical compounds due to its simplicity, sensitivity and low operational costs. DSC data indicated that the degree of purity of terazosin HYDROCHLORIDE is similar to that found by official method.

Purpose: An improved and economical method has been described for the synthesis of erlotinib HYDROCHLORIDE, as a useful drug in treatment of non-small-cell lung cancer.Methods: Erlotinib HYDROCHLORIDE was synthesized in seven steps starting from 3, 4-dihydroxy benzoic acid. In this study, we were able to modify one of the key steps which involved the reduction of the 6-nitrobenzoic acid derivative to 6-aminobenzoic acid derivative. An inexpensive reagent such as ammonium formate was used as an in situ hydrogen donor in the presence of palladium/charcoal (Pd/C) instead of hydrogen gas at high pressure.Results: This proposed method proceeded with 92% yield at room temperature. Synthesis of erlotinib was completed in 7 steps with overall yield of 44%.Conclusion: From the results obtained it can be concluded that the modified method eliminated the potential danger associated with the use of hydrogen gas in the presence of flammable catalysts. It should be mentioned that the catalyst was recovered after the reaction and could be used again.

DORZOLAMIDE ophthalmic drop is one of the most common glaucoma medications but it has a short residence time in the eye. The aim of this study is to develop ocular DORZOLAMIDE HCl nanoliposomes (DRZ – nanoliposomes) and to evaluate their potential use for the treatment of ocular hypertension. Nanoliposomes were prepared using Reverse-phase evaporation vesicle (REV) and thin layer hydration (TLH) method with 7: 3 and 7: 4 molar ratios of phosphatidy lcholine: cholesterol. The physicochemical properties of the formulations were investigated. Formulations with 7: 4 lipid ratios were evaluated in terms of drug release, physical stability and ex-vivo permeation through the excised albino rabbit cornea. The rabbits in groups of 6 were treated with selected DRZ – nanoliposomes or DORZOLAMIDE solution or marketed dorzolamid preparation (Biosopt® ) and intraocular pressure (IOP) was monitored. Formulations with 7: 4 molar ratio entrapped greater amount of drug compared to those with 7: 3 lipid components ratio. DRZ – nanoliposomes with 7: 4 lipid ratio showed more transcorneal permeation than DORZOLAMIDE solution (p<0. 05); and the formulation prepared by TLH method exhibited higher permeability than that prepared by REV method (p<0. 05). The selected DRZ – nanoliposomes showed greater IOP lowering activity and a more prolonged effect compared to DORZOLAMIDE solution and Biosopt® . DRZ – nanoliposomes prepared by TLH method with 7: 4 ratios showed promising results as a candidate for the treatment of ocular hypertension.

Background and Objective: Central Serous Chorioretinopathy (CSCR) is a common retinal disorder. The aim of this study was to evaluate the effectiveness of 2% DORZOLAMIDE eye drops in accelerating the recovery from acute CSCR. Methods: This single-blind non-randomized clinical trial included a total of 45 patients with acute CSCR. The case group (26 people who received 2% Dorsolamide eye drops twice a day for three weeks) and the control group (19 people) were studied. CSCR improvement rates were evaluated and compared by fundoscopic examination and Optical Coherence Tomography (OCT) images before and three weeks after the intervention. Findings: The two groups were homogeneous in terms of age, sex, and baseline visual acuity. Patients in DORZOLAMIDE group showed a significant reduction in central macular thickness as measured by OCT for both the right (-180.36±152.74 µm, p<0.001) and left (-161.87±144.08 µm, p=0.004) eyes compared to control group. Moreover, 84.6% of patients in DORZOLAMIDE group and 21% in the control group recovered from CSCR. CSCR recurred in two male patients in the control group, while no relapse was observed in DORZOLAMIDE group within one month following treatment. Conclusion: Our findings suggest that the use of 2% DORZOLAMIDE eye drops twice daily for three weeks significantly reduces central macular thickness, disease duration, one-month recurrence, and the need for laser treatment in patients with CSCR.

Purpose: In this work a numerical method, based on the use of spectrophotometric data coupled to partial least squares (PLS) regression and net analyte preprocessing combined with classical least square (NAP/CLS) multivariate calibration, is reported for the simultaneous determination of metformin HYDROCHLORIDE (MET), gliclazide (GLZ) and pioglitazone HYDROCHLORIDE (PIO) in synthetic samples and combined commercial tablets.Methods: Spectra of MET, GLZ and PIO were recorded at concentrations within their linear ranges (5-25 mg/ml, 0.5-8 mg/ml and 0.5-3 mg/ml respectively) and were used to compute a total of 25 synthetic mixtures involving 15 calibration and 10 validation sets between wavelength range of 200 and 400 nm in 0.1N HCl. The suitability of the models was decided on the basis of root mean square error (RMSE) values of calibration and validation data.Results: The analytical performances of these chemometric methods were characterized by relative prediction errors and recovery studies (%) and were compared with each other. These two methods were successfully applied to pharmaceutical formulation, tablet, with no interference with excipients as indicated by the recovery study results. Mean recoveries of the commercial formulation set together with the figures of merit (calibration sensitivity, selectivity, limit of detection, limit of quantification etc.) were estimated.Conclusion: The proposed methods are simple, rapid and can be easily used as an alternative analysis tool in the quality control of drugs and formulation.