A study of the impact of polymer–surfactant in drug nanoparticle coated pharmatose composites on dissolution performance

Abstract

Without a proper stabilizer formulation, drug nanoparticles can aggregate during the formation of nanosuspensions and their drying into composite powders, which in turn can cause inadequate bioavailability enhancement from nanoparticles and ensuing lack of therapeutic efficacy. In this study, formulations with various polymer concentrations-molecular weights in the presence/absence of a surfactant were explored to assess their impact on redispersibility and drug dissolution from the composites. Suspensions of griseofulvin (GF), a poorly water-soluble drug, were prepared by wet stirred media milling and subsequently dried via fluidized bed dryingcoating onto Pharmatose ® carrier particles. Hydroxypropyl cellulose (HPC), with various molecular weights, sodium dodecyl sulfate (SDS), and their combinations were used as stabilizers during the milling. The dried composites were redispersed in water and SDS solution to recover the GF nanoparticles. Particle sizing via laser diffraction, SEM imaging, and dissolution testing were performed to investigate the redispersion and dissolution performance. Results show that good physical stability of the milled suspension is necessary, but not sufficient to guarantee fast redispersion-drug dissolution. For best performance, presence of SDS is critical; a minimum concentration of the polymer, as a film former, is also required to prevent the formation of hard aggregates during drying.

Redispersible spray-dried lipid-core nanocapsules intended for oral delivery: the influence of the particle number on redispersibility

“…Previous studies evaluated the aqueous redispersion of small amounts of powder with larger volumes of water, but they did not find any correlation with the original volume of the fed sample. Furthermore, a considerable number of protocols employ high temperature, surfactants or an ultrasonic bath to enable the redispersion of nanoparticles (Kaye et al 2009, Li et al 2016, Schafroth et al 2012, Sinsuebpol et al 2013, Tomoda et al 2009, Tomoda et al 2008. However, in the present study the dilution of 0.695 g of F50:50 powder in a 5-mL volumetric flask followed by vortexing for 2 min at room temperature clearly shows that redispersing the spray-dried powder could be a very simple process, since some parameters have been taken into account, like the particle density number of the sample fed to the spray-dryer.…”

Spray-Dried Amorphous Solid Dispersions of Griseofulvin in HPC/Soluplus/SDS: Elucidating the Multifaceted Impact of SDS as a Minor Component

“…A Rodos/Helos laser diffraction system (Sympatec, NJ, USA) was used to measure the particle size of the as-received GF and spray-dried samples, based on Fraunhofer theory, following the method in Li et al [47]. To examine the morphology of the spray-dried particles, samples were placed on a glass slide and observed under a polarized light microscope (PLM, Axio Scope.A1, Carl Zeiss Microscopy GmbH, Göttingen, Germany).…”

“…An assay testing was performed to determine drug content following the method in Li et al [47]. A total of 100 mg of the sample powders was dissolved in 20 mL methanol under 30 min of sonication, followed by overnight storage to ensure complete solubilization of the GF particles.…”

Bioavailability Enhancement of Poorly Water-Soluble Drugs via Nanocomposites: Formulation–Processing Aspects and Challenges

“…A major formulation challenge in dissolution enhancement upon use of drug-laden nanocomposites is that drug nanoparticles in nanocomposites may be released too slowly and/or in the form of large clusters (a.k.a. aggregates) during in vivo or vitro dissolution [ 66 , 84 , 85 , 86 , 87 ]. Besides the aggregation that may take place during the preparation/storage of drug nanosuspensions, drug nanoparticles can also aggregate into larger sub-micron clusters or even micron-sized clusters during the removal of water or solvents in the drying process, depending on the type/concentration of the dispersants [ 74 , 85 ].…”

“…Consequently, the advantages of drug nanoparticles with inherently large surface areas could be lost upon drying. The aggregates may be broadly classified as irreversible and reversible, as shown in Figure 2 [ 66 , 74 , 86 ], based on the redispersion behavior of dried nanosuspensions (nanocomposites) in liquids. Nanocomposite particles may contain aggregates of drug nanoparticles that have formed during the nanosuspension preparation step and/or drying step.…”