Comminution of ibuprofen to produce nano-particles for rapid dissolution.
ABSTRACT 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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ABSTRACT: Aqueous dispersions of solid lipid nanoparticles (SLNTM) were converted by spray-drying into dry, reconstitutable powders which could be stored over a long period. After redispersion, the resulting granulates were still acceptable for i.v. administration with respect to the particle size distribution and toxicity. Therefore only physiologically-acceptable excipients such as carbohydrates and alcohols (ethanol and methanol) were added to the SLN dispersions before spraying. The particle size was influenced by the applied spraying parameters and by the chemical nature of the lipid phase, the type of carbohydrate and the spraying, and the redispersion medium. An identical size distribution before and after the spraying process, followed by subsequent redispersion was achieved by: reducing the temperature by spraying alcoholic dispersions, reducing the lipid concentration while increasing the sugar concentration, and by redispersion in a poloxamer 188 solution.European Journal of Pharmaceutics and Biopharmaceutics 10/1998; 46(2):145-51. · 3.83 Impact Factor
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ABSTRACT: An increasing number of newly developed drugs are poorly soluble; in many cases drugs are poorly soluble in both aqueous and organic media excluding the traditional approaches of overcoming such solubility factors and resulting in bioavailability problems. An alternative and promising approach is the production of drug nanoparticles (i.e. nanosuspensions) to overcome these problems. The major advantages of this technology are its general applicability to most drugs and its simplicity. In this article, the production of nanoparticles on a laboratory scale is presented, special features such as increased saturation solubility and dissolution velocity are discussed, and special applications are highlighted, for example, mucoadhesive nanosuspensions for oral delivery and surface-modified drug nanoparticles for site-specific delivery to the brain. The possibilities of large scale production -- the prerequisite for the introduction of a delivery system to the market -- are also discussed.Advanced Drug Delivery Reviews 04/2001; 47(1):3-19. · 12.89 Impact Factor
Article: Thermodynamics on the nanoscale.[show abstract] [hide abstract]
ABSTRACT: Classical thermodynamics is applied to the melting of nanometer-sized Sn particles with radii in the range 5-50 nm. Such particles display a depression of both the melting point and the latent heat of fusion depending on the particle size. The size dependence can be explained with the formation of a structurally perturbed layer at the particle surface. The experimental measurement of both melting temperatures and latent heats of fusion allowed for estimation of the thickness of the perturbed layer. This permitted in turn the evaluation of the excess Gibbs free energy associated with the perturbed layer at melting and the determination of its variation with particle size and temperature.The Journal of Physical Chemistry B 12/2005; 109(46):21938-41. · 3.61 Impact Factor