NanoClusters Surface Area Allows Nanoparticle Dissolution with Microparticle Properties

Abstract

Poorly water soluble drugs comprise the majority of new drug molecules. Nanoparticle agglomerates, called NanoClusters, can increase the dissolution rate of poorly soluble compounds by increasing particle surface area. Budesonide and danazol, two poorly soluble steroids, were studied as model compounds. NanoCluster suspensions were made using a Netzsch MiniCer media mill with samples collected between 5 and 15 hours and lyophilized. DSC and PXRD were used to evaluate the physicochemical properties of the powders and BET was used to determine surface area. SEM confirmed NanoClusters were between 1 and 5 μm. NanoCluster samples showed an increase in dissolution rate compared to the micronized stock and similar to a dried nanoparticle suspension. BET analysis determined an increase in surface area of 8 times for budesonide NanoClusters and 10 to 15 times for danazol NanoClusters compared to micronized stock. Melting temperatures decreased with increased mill time of NanoClusters by DSC. The increased surface area of NanoClusters provides a potential micron-sized alternative to nanoparticles to increase dissolution rate of poorly water soluble drugs.

Small Airway Absorption and Microdosimetry of Inhaled Corticosteroid Particles after Deposition

“…Previous studies have proven that nanoaggregates have an improved dissolution profile (31, 56, 57). Results of the current study verify these findings with a 57-fold increase in the total absorption efficiency of FP with nanoaggregates compared with microparticles under fast clearance conditions (Table 2).…”

“…Nanoaggregates have aerodynamic diameters similar to conventional microparticles resulting in similar deposition mechanisms of impaction and sedimentation. Kuehl et al (31) report nanoaggregates with diameters in the range of 1–5 μm. Therefore, it is reasonable that a nanoaggregate aerosol delivered at the same initial dose and with a similar aerodynamic diameter would provide a very similar deposited dose profile compared with a conventional microparticle aerosol.…”

“…An identical total dose was assumed for all three particleforms in order to focus on the effects of dissolution, absorption and clearance of different particle forms without the effect of different deposited doses. Nanoaggregates are clusters of nanoparticles that form a microparticle (56, 57, 64, 65). Due to a large aerodynamic size, deposition of nanoaggregates is consistent with microparticles and occurs by impaction and sedimentation.…”

“…A variety of mathematical models are available to characterize the dissolution and absorption of particles in a solution (31–33). However, these models are typically fit to dissolution data in large volumes of liquid, neglecting the unique thin liquid layer and lipophilic wall arrangement of the airways, and do not include a clearance mechanism.…”

Preparation, Characterization, and In Vivo Study of 7-Ethyl-14-Aminocamptothecin-Loaded Poly(Ethylene Glycol)2000-Poly(Lactic Acid)2000 Polymeric Micelles Against H460 Human Nonsmall Cell Lung Carcinoma

“…A variety of drug delivery systems, such as self‐emulsion, inclusion compound, liposomes, microspheres, and amphiphilic copolymers, have been developed to enhance the solubility and antitumor activity of hydrophobic chemotherapeutic agents. Among these approaches, polymeric micelles are widely used and have attracted many researchers' attention because of its predominant advantages in drug loading (DL), stability, release, and delivery . Polymeric micelles are prepared from amphiphilic block copolymers, which have a tendency to self‐assemble into core–shell structure in aqueous solution .…”