Ultrasonic Processing Technique as a Green Preparation Approach for Diacerein-Loaded Niosomes
In this study, the feasibility of ultrasonic processing (UP) technique as green preparation method for production of poorly soluble model drug substance, diacerein, loaded niosomes was demonstrated. Also, the effects of different surfactant systems on niosomes’ characteristics were analyzed. Niosomes were prepared using both the green UP technique and traditional thin-film hydration (TFH) technique, which requires the use of environmentally hazardous organic solvents. The studied surfactant systems were Span 20, Pluronic L64, and their mixture (Span 20 and Pluronic L64). Both the production techniques produced well-defined spherical vesicles, but the UP technique produced smaller and more monodisperse niosomes than TFH. The entrapment efficiencies with the UP method were lower than with TFH, but still at a feasible level. All the niosomal formulations released diacerein faster than pure drug, and the drug release rates from the niosomes produced by the UP method were higher than those from the TFH-produced niosomes. With UP technique, the optimum process conditions for small niosomal products with low PDI values and high entrapment efficiencies were obtained when 70% amplitude and 45-min sonication time were used. The overall results demonstrated the potency of UP technique as an alternative fast, cost-effective, and green preparation approach for production of niosomes, which can be utilized as drug carrier systems for poorly soluble drug materials.
Physicochemical characterization and dissolution study of solid dispersions of diacerein with polyethylene glycol 6000
Objective: Diacerein (DCN) is a new anti-inflammatory analgesic and antipyretic drug developed specially for the treatment of osteoarthritis. DCN is a poorly water-soluble drug with relatively low bioavailability. Therefore, the purpose of this study was to enhance the solubility and dissolution of DCN by complexation with polyethylene glycol 6000 (PEG). Methods: Solid dispersions (SDs) of DCN were prepared in weight ratios of 60:40, 40:60, 20:80, and 5:95 by the melting method using PEG as carrier. These SDs were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy to ascertain whether there were any physicochemical interactions between drug and carrier that could affect dissolution. Solubility and dissolution studies were conducted with pure DCN, physical mixtures (PMs) and SDs. Results and discussion: Solubility studies indicated that PEG significantly increased the solubility of DCN in water. The Gibbs free energy (ΔGtr°) values were negative, indicating the spontaneous nature of DCN solubilization. Phase solubility studies indicated complex with a possible stoichiometry of 1:1. Conclusion: FTIR, DSC and PXRD studies indicate that there is no chemical interaction between DCN and PEG in solid state. In contrast to slow dissolution rate of pure DCN, the dispersion of drug in PEG considerably enhanced the dissolution rate. Even PMs of DCN prepared with PEG also showed better dissolution profiles compared with that of DCN, indicating the solubilization effect of PEG. Therefore, it is concluded that the preparation of SDs of DCN with PEG provides a promising way to increase its solubility and dissolution rate.
Electrophysiological Studies of Penticainide (CM 7857), a New Antiarrhythmic Agent, in Mammalian Myocardium
The intracellular electrophysiologic properties of a new antiarrhythmic substance, penticainide, were studied in isolated rabbit, dog, and guinea pig myocardial preparations superfused or perfused with oxygenated Tyrode's solution. “Therapeutic” concentrations of penticainide (1.5 to 3 x 10-5 M) had little effect on sinus node automaticity; sinoatrial conduction was slightly delayed. In atrial, Purkinje and ventricular fibers, amplitude, and maximal rate of rise of phase 0 (dV/dtmax) were decreased by penticainide; Purkinje-ventricle conduction velocity was depressed. Penticainide did not significantly modify action potential duration (APD) of rabbit atria and dog ventricle and reduced APD and effective refractory period (ERP) of dog Purkinje and guinea pig ventricular fibers. Penticainide reduced APD heterogeneity of Purkinje-ventricle junction with a preferential effect at the gate and decreased tension amplitude of perfused papillary muscle in dog heart. The effect of penticainide on dV/dtmax was voltage and rate dependent; the resting block was weak. Thus, penticainide is a class 1 antiarrhythmic agent with properties of class 1B agents such as APD reduction and properties of class 1C agents such as slow recovery kinetic of rate-dependent block.