Cryoprotection–lyophilization and physical stabilization of rifampicin-loaded flower-like polymeric micelles

Abstract

Rifampicin-loadedpoly(e-caprolactone)-b-poly(ethylene glycol) -poly(e-caprolactone) flower-like polymeric micelles display low aqueous physical stability over time and undergo substantial secondary aggregation. To improve their physical stability, the lyoprotectionlyophilization process was thoroughly characterized. The preliminary cryoprotectant performance of mono-and disaccharides (e.g. maltose, glucose), hydroxypropyl-bcyclodextrin (HPbCD) and poly(ethylene glycol) (PEG) of different molecular weights was assessed in freeze -thawing assays at 2208C, 2808C and 21968C. The size and size distribution of the micelles at the different stages were measured by dynamic light scattering (DLS). A cryoprotectant factor ( f c ) was determined by taking the ratio between the size immediately after the addition of the cryoprotectant and the size after the preliminary freeze -thawing assay. The benefit of a synergistic cryoprotection by means of saccharide/ PEG mixtures was also assessed. Glucose (1 : 20), maltose (1 : 20), HPbCD (1 : 5) and glucose or maltose mixtures with PEG3350 (1 : 20) (copolymer:cryoprotectant weight ratio) were the most effective systems to protect 1 per cent micellar systems. Conversely, only HPbCD (1 : 5) cryoprotected more concentrated drug-loaded micelles (4% and 6%). Then, those micelle/ cryoprotectant systems that displayed f c values smaller than 2 were freeze-dried. The morphology of freeze-dried powders was characterized by scanning electron microscopy and atomic force microscopy and the residual water content analysed by the Karl Fisher method. The HPbCD-added lyophilisates were brittle porous cakes (residual water was between 0.8% and 3%), easily redispersable in water to form transparent systems with a minimal increase in the micellar size, as determined by DLS.

Hybrid Titanium Oxide/Polymer Amphiphilic Nanomaterials with Controlled Size for Drug Encapsulation and Delivery

“…As expected, T m of nitazoxanide is absent, strongly suggesting the amorphous nature of the encapsulated drug due to its molecular dispersion in the copolymer. These results are in accordance with those reported elsewhere with other hydrophobic drug encapsulated within polymeric amphiphiles …”

Synthesis of non-toxic, biocompatible, and colloidal stable silver nanoparticle using egg-white protein as capping and reducing agents for sustainable antibacterial application

“…The stability of nanoparticles is an important criterion during pharmaceutical formulations, which generally changes during to freeze-thawing and freeze-drying (lyophilization process). [33][34][35][36] Hence, these variations in chemical-physical properties limit their biomedical application. Therefore, the effect of freezing-thawing and freeze-drying was investigated regarding the stability of the synthesized AgNPs-EW.…”

Biological assessment of self-assembled polymeric micelles for pulmonary administration of insulin

“…Although micelles were prepared using low concentrated polymer solutions (1% w/v), it seems that during the freeze and drying steps of lyophilization an increase in polymer concentration and/or aggregation of micelles led to the formation of the observed structures. Similar network-like structure was observed for freezedried PCL-PEG-PCL micelles (< 6% w/v) (18).…”