Fixed Bed Adsorption of Drugs on Silica Aerogel from Supercritical Carbon Dioxide Solutions

Supercritical adsorption coupled with the high adsorption capacity of silica aerogel allows the preparation of a new kind of delivery systems of poor water soluble drugs. In order to overcome drawbacks of conventional techniques where the use of liquid solvents can cause the fracture of aerogel porous structure, in this work a new adsorption process of drugs from a supercritical mixture is proposed. Adsorption takes place from a fluid solution of the drug in supercritical CO2 and ethanol as cosolvent. A fixed bed adsorption plant has been developed to allow fast mixing of fluid phase and effective contact in the adsorption column. The use of ethanol as cosolvent allows to overcome the limitation of supercritical adsorption due to low solubility of many drugs in supercritical CO2. Adsorption isotherms were measured for one-model substance, nimesulide, at 40°C, and breakthrough curve was experimentally obtained. The drug loading of the drug into silica aerogel was up to 9？wt%. The drug composite was characterized using scanning electron microscopy, and release kinetics of the adsorbed drug were also evaluated by in vitro dissolution tests. The dissolution of nimesulide from loaded aerogel is much faster than dissolution of crystalline nimesulide. Around 80% of nimesulide dissolves from the aerogel within 6 minutes, whereas dissolving 80% of the crystalline drug takes about 90？min. 1. Introduction The poor water solubility of some drugs limited their bioavailability. A fast dissolving system can be defined as a dosage form for oral administration, which, when placed in mouth, rapidly dispersed or dissolved increasing compliance and efficacy of the therapy. Fast dissolving and fast dispersing drug delivery system may offer a solution to these problems. A possible approach for ensuring maximum bioavailability is the increase of drug dissolution rate and/or solubility. To improve the dissolution rate of drugs, different techniques have been developed [1]. The most common approach is based on particle size reduction that can be achieved by processes based on micronization or nanosuspension. In the field of supercritical fluids, various promising techniques of micronization of drugs and excipients with supercritical carbon dioxide (SC-CO2) have been developed [2, 3], and also the use of water solvent and the less-expensive supercritical nitrogen is being explored [4–6]. An alternative way to improve the availability of a drug is its dispersion on a biocompatible substrate [7]. Silica-based materials used as substrate are widely employed as additives, free flow