Itraconazole

The objective of the present research work is to formulate and evaluate Itraconazole antifungal gel. Itraconazole is an imidazole derivative and used for the treatment of local and systemic fungal infection. The oral activity of Itraconazole is not much proven to be efficient as it has many side effects. This formulation is made for better patient compliance and to reduce the dose of the drug. The gel was formulated by changing the polymer ratio. Various formulation (F1, F2, F3, F4) were developed by using a suitable polymer (carbopol 971p and noveonAA1). The formulation was evaluated for, spreadability, extrudability and viscosity in vitro drug release study. Viscosity studies of various formulations revealed that formulation F4 was better to compare to others. From among all the developed formulation, F4 shows better drug diffusion, did good Rheological properties. pH of the F4 formulation is sufficient enough to treat the skin infections. Results indicated that the concentration of carbopol 971p and noveon AA1 significantly affects drug release and rheological properties of the gel. It was concluded that formulation F4 was the best formulation among this formulation. Hence formulation F4 has shown the better results compared to other batches.

The aim of the present study was to formulate and evaluate self micro emulsifying drug delivery system to enhance the solubility of the BCS class II drug, i.e. itraconazole. SMEDDS of the model drug were prepared using castor oil and benzyl alcohol as oil phase, tween 80 as surfactant and poly ethylene glycol 400 and ethanol as co-solvents. The prepared SMEDDS were characterized by SEM and zeta potential. SMEDDS were evaluated for globule size, stability studies, dispersibility test and in vitro drug release. SEM photograph showed that globules were smooth and spherical in shape. The particle size and zeta potential of prepared formulation was found to be between 8-16 µm and -11.5 to -55.6 respectively. Stability of itraconazole drug was found to depending on the amount of castor oil present in the formulation. As concentration of castor oil in the formulation increases, so the stability. In vitro drug release of the formulations was carried out in pH 1.2 buffer for 2 hours. Formulation F6 showed 98.50% drug release at the end of 2 hours. It was concluded that the SMEDDS prepared seem to promising carriers for enhancing the bioavailability and the solubility of poorly water soluble drug.

A simple, precise, and rapid high performance liquid chromatography (HPLC) method for the determination of ketoconazole level in human plasma using itraconazole as an internal standard (IS) was developed and validated. 0.25 ml plasma samples containing ketoconazole were mixed with 15 µg of the IS. After adding 0.25 ml acetonitrile, the mixture was vortexed for two minutes and then centrifuged for 10 minutes at 16000 rpm at room temperature. The clear supernatant was transferred into an auto-sampler vial, and 100 µl was injected into the HPLC system with a run time of 10 min. The compounds of interest were efficiently separated on 4.6 x 150 mm, Symmetry Shield TMRP18 5-µm steel column, using a Guard Pak pre-column module with    Radial-Pak C18 5-µm insert, and detected using Waters 2475 multi λ fluorescence detector with an the excitation and emission wavelengths set at 260 and 375 nm, respectively. The mobile phase consisted of 0.02 M potassium dihydrogen phosphate (pH = 6.0, adjusted with 0.1 M sodium hydroxide) and acetonitrile (40:60, v:v), and was delivered at a flow rate of 1.0 ml/min. No interference from blank plasma or commonly used drugs was observed; and the detection limit of ketoconazole was 0.1 µg/ml. The relationship between ketoconazole concentration in plasma and peak area ratio of ketoconazole /IS was linear (r2 ≥ 0.9979) in the range of 0.1– 20 µg/ml. Intra- and inter-day coefficients of variation (CV) were ≤ 8.1%  and  ≤ 9.7%, respectively, with corresponding biases of ≤ -13% and ≤ 0.9%, respectively. Mean extraction recovery of ketoconazole and IS were ≥ 85% and 92%, respectively. Using the method, ketoconazole was found to be stable for 48 hrs at -20°C (≥ 95%) in processed samples and for 8 weeks at -20°C (100%) in unprocessed samples. Key words: Ketoconazole, Itraconazole, Human plasma, HPL

This study investigated the spherical agglomeration of itraconazole for enhanced drug dissolution rate and bioavailability at various polymers percentage like 0.2%, 0.4%and 0.6% with Soluplus®, HPMC and PEG-4000 by simple stirring at 900 r.p.m. (The spherical agglomerates(SA) were dried powdered and with method followed by characterized by differential scanning calorimetry and X-ray powder diffraction. The SAs of itraconazole were also evaluated by drug content study, solubility study and in-vitro dissolution study. The pharmacokinetic studies of the formulations and pure itraconazole were evaluated i.e. Cmax, Tmax and AUC   in vivo study by pharmacokinetic model on wistar rats.

The present study deals with the formulation and evaluation of egg albumin based delayed release microspheres of itraconazole, which is drug of choice for systemic fungal infections. The study was undertaken in order to achieve the best possible drug-polymer (egg albumin) ratio to get delayed drug release using natural biodegradable polymer. The preparation of microsphere was done by using heat denaturation technique. The prepared microspheres were evaluated on various parameters like the size, morphology, micromeritic properties, percent drug entrapment, in-vitro dissolution studies and the scanning electron microscopy (SEM).The in vitro dissolution studies were carried out for 10 hrs. at pH 6.8 which showed that the drug release for the batch EA4 (drug: polymer ratio – 1:4) was 87.02 ± 5.89 after 10 hrs. The hypothesis of this research work i.e delayed drug release using natural biodegradable polymer was well supported by results of its evaluation.

  Itraconazole, a poorly water soluble antimycotic agent, is promising agent for various diseases. To improve the solubility of itraconazole, the inclusion compound of Itraconazole with β-cyclodextrin was prepared by spray drying, solvent evaporation, kneading, lyophilization, physical mixture method and characterized by solubility, scanning electron microscopy, differential scanning calorimetry, FTIR and dissolution study. DSC and FTIR confirmed the formation of complex. The solubility of the prepared complex was found to be improved. Itraconazole complex by spray drying method and Itraconazole showed 95.65 % and 80.55% of drug release at the end of 48 h in dissolution study. It was concluded that the complex of itraconazole may be of potential use for improving the solubility of itraconazole and hence its bioavaibility.