Morphological and Physicochemical Evaluation of Two Distinct Glibenclamide/Hypromellose Amorphous Nanoparticles Prepared by the Antisolvent Method

Abstract

The morphology and stability of amorphous nanoparticles of glibenclamide (GLB) prepared by the antisolvent method using different methods of adding hypromellose (HPMC) were evaluated. Nano-A was prepared by the injection of a dimethyl sulfoxide (DMSO) solution of GLB into the HPMC solution, whereas nano-B was obtained by the injection of a DMSO solution of GLB and HPMC into water. Cryogenic transmission electron microscopy, field-emission scanning electron microscopy, and field-emission transmission electron microscopy, including energy dispersive X-ray spectrometry, revealed that the particles of the nano-A and nano-B samples are hollow spheres and nonspherical nanoparticles, respectively. Powder X-ray diffraction and solid-state NMR measurements showed that GLB is present in an amorphous state in both nano-A and nano-B. The weight ratios of HPMC in the GLB/HPMC nanoparticles were 11 and 16% for nano-A and nano-B, respectively, as determined by solution-state NMR. The glass transition temperatures ( T) of nano-A and nano-B evaluated using differential scanning calorimetry were lower by about 10 °C compared to that of amorphous GLB, presumably because of a T confinement effect and the surface coverage and mixing of HPMC, as suggested by the inverse gas chromatography experiment. GLB crystallization during storage was suppressed more strongly in nano-B than nano-A, owing to the higher amount of HPMC and the higher miscibility between GLB and HPMC. It is suggested that the diffusion rate of the solvent during nanoprecipitation determined the nanoparticle properties. In nano-A, the precipitation of GLB first occurred at the outer interface because of the rapid diffusion of the solvent. Thus, hollow spherical particles with HPMC preferentially located near the surface were formed. On the other hand, the diffusion of the solvent in nano-B was suppressed because of the presence of HPMC, yielding small nonspherical nanoparticles with a high miscibility of GLB and HPMC.

Cryo-TEM and AFM Observation of the Time-Dependent Evolution of Amorphous Probucol Nanoparticles Formed by the Aqueous Dispersion of Ternary Solid Dispersions

“…HPMC, which has a T g of approximately 160 °C, could enhance the T g in the GMs, although most of the HPMC dissolved into the water after aqueous dispersion (Table ). Furthermore, the T g confinement effect due to the size reduction and the inclusion of water ( T g = −138 °C) in the nanoparticles could also reduce the T g of the nanoparticles. − Therefore, the amorphous PBC in the nanoparticles in water was more likely in a supercooled liquid state than in a glass state. The extremely soft structure of the nanoparticles, as demonstrated in the AFM force–distance curve measurement (Figure ), could be derived from this supercooled liquid state of PBC.…”

Design of Redispersible High-Drug-Load Amorphous Formulations: Impact of Ionic vs Nonionic Surfactants on Processing and Performance

“…Submicron amorphous drug nanoparticles were developed using solvent/antisolvent precipitation , with the goal of decreasing particle size of ASD to increase dissolution rate and supersaturation level. , Hydrophilic hydroxypropyl methylcellulose used in the solvent/antisolvent precipitation oriented preferentially on the surface of particles, which effectively enabled formation of amorphous particles of decreased sizes . Building upon the concept, a confined impinging jet − and a multi-inlet vortex mixer (MIVM) were developed to better control the mixing dynamics that enabled generation of narrow distribution of nanoparticles using block copolymers as stabilizing agents. , Size distribution and structure of the nanoparticles can be controlled by adjusting liquid streamflow rates, viscosity (imparted by polymer/surfactant), pH, and incorporation of components in one or separated streams. ,,, However, processing these nanoparticle suspensions into a final solid dosage form remained a challenge. Many studies pursued drying of the nanoparticle suspension directly after generation through spray-drying (SD) and freeze-drying (FD).…”

“…23,24 Size distribution and structure of the nanoparticles can be controlled by adjusting liquid streamflow rates, viscosity (imparted by polymer/surfactant), pH, and incorporation of components in one or separated streams. 17,20,25,26 However, processing these nanoparticle suspensions into a final solid dosage form remained a challenge. Many studies pursued drying of the nanoparticle suspension directly after generation through spray-drying (SD) and freeze-drying (FD).…”

Amorphous Nanosuspensions Aggregated from Paclitaxel–Hemoglobulin Complexes with Enhanced Cytotoxicity

“…Nanosuspensions of insoluble drugs, in which the drug can exist in crystalline or amorphous form, are a promising nanomedicine, possessing merits including extremely high drug-loading capacity, easy preparation, enhanced dissolution rate and saturation solubility, reproducibility, improved dose-bioavailability proportionality and increased patient compliance [ 4 , 5 , 6 ]. In contrast with crystalline nanosuspensions, amorphous nanosuspensions (ANSs) with unordered arrangement of molecules allow for faster dissolution rate and higher solubility [ 7 , 8 , 9 ].…”