Ibuprofen nanocrystals developed by 22 factorial design experiment: A new approach for poorly water-soluble drugs

Abstract

The reduction of the particle size of drugs of pharmaceutical interest down to the nano-sized range has dramatically changed their physicochemical properties. The greatest disadvantage of nanocrystals is their inherent instability, due to the risk of crystal growth. Thus, the selection of an appropriate stabilizer is crucial to obtain long-term physicochemically stable nanocrystals. High pressure homogenization has enormous advantages, including the possibility of scaling up, lack of organic solvents and the production of small particles diameter with low polydispersity index. The sequential use of high shear homogenization followed by high pressure homogenization, can modulate nanoparticles' size for different administration routes. The present study focuses on the optimization of the production process of two formulations composed of different surfactants produced by High Shear Homogenization followed by hot High Pressure Homogenization. To build up the surface response charts, a 2 full factorial design experiment, based on 2 independent variables, was used to develop optimized formulations. The effects of the production process on the mean particle size and polydispersity index were evaluated. The best ibuprofen nanocrystal formulations were obtained using 0.20% Tween 80 and 1.20% PVP K30 (F1) and 0.20% Tween 80 and 1.20% Span 80 (F2). The estimation of the long-term stability of the aqueous suspensions of ibuprofen nanocrystals was studied using the LUMISizer. The calculated instability index suggests that F1 was more stable when stored at 4 °C and 22 °C, whereas F2 was shown to be more stable when freshly prepared.

Improved rheological properties and stability of multiwalled carbon nanotubes/polymer in harsh environment

“…The instability index is a dimensionless number and ranges from 0 (more stable) to 1 (more unstable). In fact, for the same total clarification, samples with high clarification rates tend to be more unstable …”

Design Space and QbD Approach for Production of Drug Nanocrystals by Wet Media Milling Techniques

“…In this preliminary phase, the CPPs affecting selected CQAs are recognized [ 86 ]. In order to study more precisely the impact of certain variables, design setups can be utilized; the 2 2 factorial design set-up was utilized for studying the effect of concentration levels of two different stabilizers [ 87 ], 3 2 factorial design to study the effect of stabilizer concentration and antisolvent–solvent ratio on particle size, drug content and 90% drug release time [ 88 ], 3 2 factorial design to study the effect of amount of stabilizer and process time [ 89 ], or Box–Behnken design was used for studying the effect of drug, polymer and surfactant concentrations and milling time [ 77 ] or polymer and surfactant concentrations and milling time and speed and the final product properties determined were particle size distribution, zeta-potential and scalability of the process [ 76 ]. Utilization of design setups can minimize the number of tests to be performed but maximize the information gained.…”

Solubilization of ibuprofen for freeze dried parenteral dosage forms

“…Ibuprofen (IBP) is a weak acid, classified as BCS Class II (6) drug. It is a member of the well-established nonsteroidal anti-inflammatory drugs (NSAIDs) and is widely used for acute or chronic pain relief.…”