Comminution of ibuprofen to produce nano-particles for rapid dissolution

Lena Nanoceutics Ltd., Institute of Pharmaceutical Innovation, Bradford BD7 1DP, UK.
International Journal of Pharmaceutics (Impact Factor: 3.65). 06/2011; 415(1-2):307-14. DOI: 10.1016/j.ijpharm.2011.06.002
Source: PubMed


A critical problem associated with poorly soluble drugs is low and variable bioavailability derived from slow dissolution and erratic absorption. The preparation of nano-formulations has been identified as an approach to enhance the rate and extent of drug absorption for compounds demonstrating limited aqueous solubility. A new technology for the production of nano-particles using high speed, high efficiency processes that can rapidly generate nano-particles with rapid dissolution rate has been developed. Size reduction of a low melting ductile model compound was achieved in periods less than 1h. Particle size reduction of ibuprofen using this methodology resulted in production of crystalline particles with average diameter of approximately 270nm. Physical stability studies showed that the nano-suspension remained homogeneous with slight increases in mean particle size, when stored at room temperature and under refrigerated storage conditions 2-8°C for up to 2 days. Powder containing crystalline drug was prepared by spray-drying ibuprofen nano-suspensions with mannitol dissolved in the aqueous phase. Dissolution studies showed similar release rates for the nano-suspension and powder which were markedly improved compared to a commercially available drug product. Ibuprofen nano-particles could be produced rapidly with smaller sizes achieved at higher suspension concentrations. Particles produced in water with stabilisers demonstrated greatest physical stability, whilst rapid dissolution was observed for the nano-particles isolated in powder form.

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    • "slurry viscosity, size of milling beads and milling speed are involved, influencing particle size distribution as a function of time (size reduction rate) but not the steady state particle size of the NPs obtained. The later mainly depends on the intrinsic physicomechanical properties of the drug crystals as brittleness, yield stress, plasticity and elasticity (Lee, 2003; Plakkot et al., 2011). Furthermore, the inability of Pluronic 1 L64 to stabilise the indomethacin nanosuspensions seems to be interesting, especially when compared with the high success rate of Pluronic 1 F68 in stabilising nanosuspensions of indomethacin (Fig. 2) and of other poorly water-soluble drugs (Illum et al., 1987; Karmwar et al., 2012). "
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