Oral delivery strategies for the controlled release of cimetidine

It is advantageous to develop controlled release dosage forms utilising site-specific delivery or gastric retention for those drugs with frequent or high dosing regimes. Cimetidine is a potent and selective H2 -reception antagonist used in the treatment of various gastrointestinal disorders and localisation in the upper gastrointestinal tract could significantly improve the drug absorption. Three strategies were undertaken to prepare controlled release systems for the delivery of cimetidine to the GI tract. Firstly, increasing the contact time of the dosage form with the mucus layer which coats the gastrointestinal tract, may lead to increased gastric residence times. Mucoadhesive microspheres, by forming a gel-like structure in contact with the mucus, should prolong the contact between the delivery system and the mucus layer, and should have the potential for releasing the drug in sustained and controlled manner. Gelatin microspheres were prepared, optimised and characterised for their physicochemical properties. Crosslinking concentration, particle size and cimetidine loading influenced drug release profiles. Particle size was influenced by surfactant concentration and stirring speed. Mucoadheisve polymers such as alginates, chitosans, carbopols and polycarbophil were incorporated into the microspheres using different strategies. The mucoadhesion of the microspheres was determined using in vitro surface adsorption and ex vivo rat intestine models. The surface-modification strategy resulted in highest levels of microsphere adhesion, with chitosan, carbopols and polycarbophil as the most successful candidates for improvement of adhesion, with over 70% of the microspheres retained ex vivo. Specific targeting agent UEA I lectin was conjugated to the surface of gelatin microspheres, which enhanced the adhesion of the microspheres. Alginate raft systems containing antacids have been used extensively in the treatment of gastro-oesophageal disease and protection of the oesophageal mucosa from acid reflux by forming a viscous raft layer on the surface of the stomach content, and could be an effective delivery system for controlled release of cimetidine.

Four-leg converters with improved common current sharing and selective voltage-quality enhancement for islanded microgrids

Four-leg dc-ac power converters are widely used for the power grids to manage grid voltage unbalance caused by the interconnection of single-phase or three-phase unbalanced loads. These converters can further be connected in parallel to increase the overall power rating. The control of these converters poses a particular challenge if they are placed far apart with no links between them (e.g., in islanded microgrids). This challenge is studied in this paper with each four-leg converter designed to have improved common current sharing and selective voltage-quality enhancement. The common current sharing, including zero sequence component, is necessary since loads are spread over the microgrid and they are hence the common responsibility of all converters. The voltage-quality enhancement consideration should however be more selective since different loads have different sensitivity levels towards voltage disturbances. Converters connected to the more sensitive load buses should therefore be selectively triggered for compensation when voltage unbalances at their protected buses exceed the predefined thresholds. The proposed scheme is therefore different from conventional centralized schemes protecting only a common bus. Simulation and experimental results obtained have verified the effectiveness of the proposed scheme when applied to a four-wire islanded microgrid.