Understanding a relaxation behavior in a nanoparticle suspension for drug delivery applications.
Nanoparticle dispersion has demonstrated its effectiveness in improving the dissolution rate and oral bioavailability of poorly water-soluble compounds. When we studied the interactions of drug and polymeric stabilizers and milling parameters of a poorly water-soluble compound, Compound A, the relaxation behavior that occurred repeatedly in our nanoparticle dispersion formulation was observed. Nanomill was used to generate the nanoparticle dispersion, and milling parameters such as time, speed, and stabilizer loading were altered to investigate their effects on relaxation. The particle size and morphology of milled products were studied using a light-scattering particle analyzer and a scanning electron microscope (SEM). X-ray powder diffraction (XRD) was employed to characterize particle crystallinity and the crystallite size. The results indicated that, after milling, nanoparticles agglomerated constantly to form clusters and reached maximum apparent size within the first 24h. Thereafter, the clusters relaxed spontaneously and, within a few days, dissociated into individual primary particles and the suspension were stable at sub 100-nm levels near equilibrium. Milling crystalline drug substance resulted in an XRD pattern in which the peaks were observed to broaden, suggesting formation of disordered nanocrystalline. Altering milling conditions and stabilizer ratios influences the relaxation behavior and certainly led to optimization of the process and performance of nanoparticle suspension formulations.
Deng
Z
Z
Department of Analytical Development, 1010 Joaquin Road, M4-2A, ALZA Corp., Mountain View, CA 94043, USA. rdeng@alzus.jnj.com
Xu
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Li
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D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003460:Crystallization; D004355:Drug Stability; D008027:Light; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry*; D012542:Scattering, Radiation; D012995:Solubility; D013535:Suspensions; D013678:Technology, Pharmaceutical / Q000379:methods*; D013997:Time Factors; D014961:X-Ray Diffraction
D004364:Pharmaceutical Preparations; D013535:Suspensions