An innovative antisolvent precipitation process as a promising technique to prepare ultrafine rifampicin particles

Abstract

a b s t r a c tMany existing and new drugs fail to be fully utilized because of their limited bioavailability due to poor solubility in aqueous media (BCS drug classes II and IV). In this work, for accelerating dissolution of this kind of poorly water-soluble drugs, an antisolvent precipitation method that does not require the use of conventional volatile organic solvents is proposed. To demonstrate this technique, ultrafine particles of rifampicin were prepared using a room temperature ionic liquid (1-ethyl 3-methyl imidazolium methyl-phosphonate) as an alternative solvent and a phosphate buffer as an antisolvent.Rifampicin solubility was measured in various solvents (1-ethyl 3-methyl imidazolium methylphosphonate, water and phosphate buffer), showing the RTIL good solvency for the model drug: rifampicin solubility was found to be higher than 90 mg/g in RTIL at 30 1C and lower than 1 mg/g in water at 25 1C. Additionally, it was demonstrated that introduction of rifampicin solution in 1-ethyl 3-methyl imidazolium methyl-phosphonate into the aqueous solution antisolvent can produce particles in the submicron range with or without hydroxypropyl methylcellulose as the stabilizer. The ultrafine particles (280-360 nm) are amorphous with enhanced solubility and faster dissolution rate. To our knowledge, this is the first published work examining the suitability of using RTILs for ultrafine drug nanoparticles preparation by an antisolvent precipitation process.

Response Surface Methodology for Optimization of Process Variables of Atorvastatin Suspension Preparation by Microprecipitation Method Using Desirability Function

“…Production of microcrystals refers to the formation of an additional surface area and interfaces. 30 Solubility results showed that the crystals that were prepared using Brij 35 has shown the highest solubility of the drug in water (9.99-41.84 mg/ml) as compared with the untreated drug (0.036 mg/ml) ( Table 2).…”

Towards a Greener Pharmacy by More Eco Design

“…If the use of spherical crystallization [46] and the quasi emulsion solvent diffusion (QESD, Fig. 7) method has been well known to improve the properties of active ingredients [47], an antisolvent process involving ionic liquids was used recently to prepare ultrafine rifampicyne particles [48].…”

Solubility of a New Antiretroviral Drug (Crs 74) in Aqueous Ethanol Mixtures

“…Micro/nanonization during crystallization (Rasenack and Müller, 2002;Rasenack and Müller, 2004;Badawi et al, 2011;Viçosa et al, 2012), surface modification (Han et al, 2011) and crystal structure modification (Eerdenbrugh et al, 2009) may improve the dissolution rate of poorly water-soluble APIs (Active Pharmaceutical Ingredients).…”

“…One goal in this crystallization operation is the control of product properties, e.g., particle size and particle size distribution (Zhao et al, 2007;Zhang et al, 2009), purity, residual solvent content, crystallinity, polymorphic form (Balani et al, 2010) and dissolution rates in specific media during in vitro-tests (Viçosa et al, 2012;Plakkot et al, 2011) to a certain extent. The product properties can be manipulated by changing the process parameters and formulation.…”