Multi-Layer Self-Nanoemulsifying Pellets: an Innovative Drug Delivery System for the Poorly Water-Soluble Drug Cinnarizine

Abstract

Beside their solubility limitations, some poorly water-soluble drugs undergo extensive degradation in aqueous and/or lipid-based formulations. Multi-layer self-nanoemulsifying pellets (ML-SNEP) introduce an innovative delivery system based on isolating the drug from the self-nanoemulsifying layer to enhance drug aqueous solubility and minimize degradation. In the current study, various batches of cinnarizine (CN) ML-SNEP were prepared using fluid bed coating and involved a drug-free self-nanoemulsifying layer, protective layer, drug layer, moisture-sealing layer, and/or an anti-adherent layer. Each layer was optimized based on coating outcomes such as coating recovery and mono-pellets%. The optimized ML-SNEP were characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), in vitro dissolution, and stability studies. The optimized ML-SNEP were free-flowing, well separated with high coating recovery. SEM showed multiple well-defined coating layers. The acidic polyvinylpyrrolidone:CN (4:1) solution presented excellent drug-layering outcomes. DSC and XRD confirmed CN transformation into amorphous state within the drug layer. The isolation between CN and self-nanoemulsifying layer did not adversely affect drug dissolution. CN was able to spontaneously migrate into the micelles arising from the drug-free self-nanoemulsifying layer. ML-SNEP showed superior dissolution compared to Stugeron® tablets at pH 1.2 and 6.8. Particularly, on shifting to pH 6.8, ML-SNEP maintained > 84% CN in solution while Stugeron® tablets showed significant CN precipitation leaving only 7% CN in solution. Furthermore, ML-SNEP (comprising Kollicoat® Smartseal 30D) showed robust stability and maintained > 97% intact CN within the accelerated storage conditions. Accordingly, ML-SNEP offer a novel delivery system that combines both enhanced solubilization and stabilization of unstable poorly soluble drugs.

Stabilization benefits of single and multi-layer self-nanoemulsifying pellets: A poorly-water soluble model drug with hydrolytic susceptibility

“…SL-SNEP and ML-SNEP were prepared using a bottom-spray Mycrolab® fluid bed coater (Oystar Huttlin, Schopfheim, Germany) [ 23 , 24 ]. Initially, the sugar spheres (850–1000 μm) were charged into preheated fluid bed chamber.…”

“…Solidification of CN liquid SNEDDS, by fluid bed coating, would be a novel approach because it would combine the advantages of liquid SNEDDS and multiparticulate pellets in one dosage form [ 23 ]. Our recent studies involved solidification of CN liquid SNEDDS into single-layer self-nanoemulsifying pellets (SL-SNEP) [ 23 ] and multi-layer self-nanoemulsifying pellets (ML-SNEP) [ 24 ].…”

“…To eradicate the problem completely, CN has to be isolated from solid SNEDDS, during and after manufacturing. To fulfill such requirements, an innovative approach has been recently adopted to prepare the multi-layered self-nanoemulsifying pellets (ML-SNEP) [ 24 ]. These ML-SNEP were designed to involve multiple coating layers where the drug-free SNEDDS would be coated in one layer.…”

Bioactive Self-Nanoemulsifying Drug Delivery Systems (Bio-SNEDDS) for Combined Oral Delivery of Curcumin and Piperine

“…Micrographs of the samples were taken using a scanning electron microscope (SEM) (Zeiss EVO LS10; Cambridge, United Kingdom). Samples were fixed on stubs using double sided adhesive carbon tape (SPI Supplies, West Chester, PA, USA) then coated with gold in a Q150R sputter coater unit under vacuum (Quorum Technologies Ltd, East Sussex, United Kingdom) in an argon atmosphere (20 mA) for 60 seconds [68,69].…”

Optimization of the Method for Obtaining Nanocapsules, Development of the Methods of Determining the Degree of Cinnarizine Inclusion in a Prolonged Dosage Form Based on Poly-D, L-Lactid-Co-Glicolide, and Its Validation

“…Объектом исследования послужил водный раствор супернатанта, получаемый после центрифугирования [10][11][12][13][14]. Супернатант помещали в мерную колбу вместимостью 100 мл, доводили до метки водой очищенной (раствор А).…”