Abstract:
Low water solubility and dissolution rates limit the bioavailability of poorly water soluble drugs. The dissolution rate of such solid active pharmaceutical ingredients (APIs) can be increased by precipitating these APIs as nanoparticles or microparticles . Decrease in size due to nanoparticle or microparticle formation increases the surface area and hence results in an increase in their dissolution rate in aqueous media of body fluid. However, an increase in surface area also increases the surface energy of particles and results into enhanced inter-particle interactions such as van der Waals interaction, electrostatic interaction and hydrophobic interaction. This further leads to particle coagulation and agglomeration. Use of aqueous suspensions enables easier control over crystal growth and particle agglomeration or aggregation and hence, can result into suspensions with stable particle size and size distribution. In order to produce ultrafine particles of APIs, a several techniques are available and are used in practice. However, control of particle size and size distribution, and the process scalability in comparison to liquid-antisolvent (LAS) precipitation is difficult for many of these techniques. Therefore, in this work, LAS precipitation technique is used to prepare aqueous suspensions of ultrafine particles of a poorly water soluble drug, curcumin. Curcumin is an ingredient found in traditional Indian spice, ‘turmeric’ (curcumin longa) and has potential antioxidant, antitumor, and antimicrobial properties. The LAS precipitation of curcumin particles was carried out in presence of ultrasound to improve micro-mixing and induce rapid nucleation and stabilizers to inhibit particle growth and increase nucleation rates. The objectives of this study were understand the crystallization pathway followed by precipitated particles under different operating conditions in LAS precipitation and to develop a criterion which can be used as a guide to prepare stable aqueous suspensions of ultrafine particles of poorly water soluble drugs with sizes less than 1μm.Efforts have then been made to identify kinetic and thermodynamic process parameters that affect the nucleation rates and hence, the particle sizes and stability of aqueous suspensions of curcumin particles.