Yes / Purpose: Dexibuprofen is an enantiomer of ibuprofen with low bioavailability which results from its hydrophobic nature. Nanosuspensions have developed a podium to solve the in vitro dissolution problem that frequently occurs in current research. Materials and methods: The drug and polymer solutions were mixed in a microchannel fluid reactor and the successive embryonic nanosuspension was decanted into a vial having the polymer solution. The impact of different process and formulation parameters including inlet angle, antisolvent and solvent flow rate(s), mixing time, drug concentration, polymer type and concentration was evaluated. Results and discussion: Stable dexibuprofen nanocrystals with a particle size of 45±3.0 nm and polydispersity index of 0.19±0.06 were obtained. Differential scanning calorimetry and powder X-ray diffraction confirmed the crystallinity. The key parameters observed were inlet angle 10°, antisolvent to solvent volume of 2.0/0.5 mL/min, 60 minutes mixing with 5 minutes sonication, Poloxamer-407 with a concentration of 0.5% w/v and drug concentration (5 mg/mm). The 60-day stability studies revealed that the nanocrystals were stable at 4°C and 25°C. The scanning electron microscopy and transmission electron microscopy images showed crystalline morphology with a homogeneous distribution. Conclusion: Stable dexibuprofen nanocrystals with retentive distinctive characteristics and having marked dissolution rate compared to raw and marketed formulations were efficiently fabricated. In future perspectives, these nanocrystals could be converted to solid dosage form and the process can be industrialized by chemical engineering approach

Advanced drug delivery systems have shown immense success through nanotechnology which overcomes the challenges posed by large sized particles such as poor solubility, bioavailability, absorption, and target-specific delivery. This study focuses on nano sizing by application of microreactor technology and nanoparticles to obtain polymeric particulate with a selection of model drugs for inhalation drug delivery routes. The development of nanoparticles of two challenging compounds in terms of solubility and permeability, namely Ibuprofen (IBU) and Salmeterol (SAL), was conducted using a continuous, controlled, and scalable system offered by microfluidic reactor with the incorporation of anti-solvent approach. The research explores the potential of this technology to enhance absorption rate and hence bioavailability of IBU via oral route, and SAL via inhalation. IBU, an anti-inflammatory drug, is classified as BCS Class II drug with low solubility and high permeability. SAL is a selective long acting β2-agonist which is co-dispensed along with a short-acting β2-agonist for quick relief of acute bronchoconstriction due to its long onset of action. This lack of the ‘kick’ effect in SAL can be attributed to its relatively higher lipophilicity which causes a delay in the diffusion to the β2 receptors on the smooth muscles. It is therefore feasible to assume that increasing the dissolution and/or diffusion rate of SAL in the interstitial fluids would reduce the delay between administration and the onset of action of this drug which would be beneficial to patients. Process and formulation parameters were investigated to optimize the production and stability of nano particles of both drugs using Y shaped microfluidic reactors. IBU results show that the smaller the angle between the two inlets were the smaller the particle size achieved. Moreover, the particle size increased with increasing the concentration of IBU solution. The effect of the polymer mixture ratio (PVP/HPMC) on the initial particle size was not clear though. The smallest particle size (113 nm) was achieved using 10° Y shaped chip with IBU concentration of 1 mg/mL and a polymer mixture of 0.3% w/v PVP and 0.5% w/v HPMC. Using a polymer mixture of 0.5% w/v of each polymer though yielded a better PDI (140nm and PDI of 0.5). Same observations were noted when the syringe pumps were replaced with a non-pulsatile pressure pump. Particle size though dropped significantly to 33nm. Stability data showed that all systems were practically stable regardless of the process or formulation parameters. In addition, a considerable 2.5 fold increase in dissolution rate was observed in the first 20 minutes when compared to the raw material. The optimized parameters were applied to SAL to produce nanocrystals with best result (59 nm) were obtained using 50µg/mL Salmeterol with microfluidics inlet angle 10° with non-pulse syringe pump. The stabilizing mixture was PVP 0.8% w/v and Tween 80 at a concentration of 0.02%. This approach offered a basis for the generation of nano sized SAL particles with higher fine particle fraction and better deposition in NGI than currently marketed formulations, thus providing a more efficient drug dose delivery and lung deposition.