An advantageous technique to load drugs into aerogels: Gas antisolvent crystallization inside the pores

Over the past few years, both organic and inorganic nanoporous aerogels have shown a great promise as drug delivery vehicles. Different methods are utilized to load drugs into aerogels such as the addition of the drug to the reaction mixture in one of the steps before the gel formation or by supercritical deposition to the aerogels. These techniques have disadvantages such as possible reactions of pharmaceutical compounds with reactants used to form gels and low solubility of pharmaceutical compounds in supercritical carbon dioxide (scCO(2)). An alternative technique is to load the drug after gel formation by contacting the gel with a solution of the drug. The drug diffuses into the liquid inside the pores. When this drug-loaded gel is subjected to supercritical drying, scCO(2) not only removes the solvent from the pores but also acts as an antisolvent, which causes the precipitation of the drug in the pores of the aerogel. This is similar to the gas antisolvent crystallization (GAS) process but in this case the process takes place inside the pores. In this study, this technique was used to load paracetamol into silica aerogels. The factors affecting the amount and distribution of the drug inside the aerogel matrix were investigated and a mathematical model to account for the movement of paracetamol inside the pores during supercritical drying leading to a varying drug concentration in the matrix with position was developed. It was concluded that high initial concentrations resulted in more homogeneous drug distributions. Moreover, XRD analysis demonstrated that paracetamol was in crystalline form. The process enables higher amount of loadings than conventional systems and also offers an advantage as it combines two processes such as drying and loading in a single one reducing the time and the operating expenses. (C) 2016 Elsevier B.V. All rights reserved.