Design of Olanzapine/Lutrol Solid Dispersions of Improved Stability and Performances

Cavallari, Cristina; Fini, Adamo; Ceschel, G. C.

doi:10.3390/pharmaceutics5040570

Cited by 24 publications

(13 citation statements)

References 13 publications

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“…The PEO single polymer was extruded at 100 • C and allowed a single pneumatic extrusion without any other excipients (P1 in Table 2). However, when the PEO was mixed with 5% OLZ (F1 in Table 3), the printing temperature of ODF was approximately 170 • C owing to the effect of OLZ with a high melting point [40]. A high printing temperature was not appropriate because the loaded material burned quickly before printing.…”

Section: Optimization Of Polymeric Carrier Composition For Odf Printingmentioning

confidence: 99%

Orodispersible Polymer Films with the Poorly Water-Soluble Drug, Olanzapine: Hot-Melt Pneumatic Extrusion for Single-Process 3D Printing

et al. 2020

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Amorphous solid dispersions (ASDs) improve the oral delivery of poorly water-soluble drugs. ASDs of olanzapine (OLZ), which have a high melting point and low solubility, are performed using a complicated process. Three-dimensional (3D) printing based on hot-melt pneumatic extrusion (HMPE) is a simplified method for producing ASDs. Unlike general 3D printing, printlet extrusion is possible without the preparation of drug-loaded filaments. By heating powder blends, direct fused deposition modeling (FDM) printing through a nozzle is possible, and this step produces ASDs of drugs. In this study, we developed orodispersible films (ODFs) loaded with OLZ as a poorly water-soluble drug. Various ratios of film-forming polymers and plasticizers were investigated to enhance the printability and optimize the printing temperature. Scanning electron microscopy (SEM) showed the surface morphology of the film for the optimization of the polymer carrier ratios. Differential scanning calorimetry (DSC) was used to evaluate thermal properties. Powder X-ray diffraction (PXRD) confirmed the physical form of the drug during printing. The 3D printed ODF formulations successfully loaded ASDs of OLZ using HMPE. Our ODFs showed fast disintegration patterns within 22 s, and rapidly dissolved and reached up to 88% dissolution within 5 min in the dissolution test. ODFs fabricated using HMPE in a single process of 3D printing increased the dissolution rates of the poorly water-soluble drug, which could be a suitable formulation for fast drug absorption. Moreover, this new technology showed prompt fabrication feasibility of various formulations and ASD formation of poorly water-soluble drugs as a single process. The immediate dissolution within a few minutes of ODFs with OLZ, an atypical antipsychotic, is preferred for drug compliance and administration convenience.

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Section: Optimization Of Polymeric Carrier Composition For Odf Printingmentioning

confidence: 99%

Orodispersible Polymer Films with the Poorly Water-Soluble Drug, Olanzapine: Hot-Melt Pneumatic Extrusion for Single-Process 3D Printing

et al. 2020

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“…Due to the potential ability of the nanosystems to load pharmacologically active molecules, olanzapine [32] was selected as a model drug.…”

Section: Olanzapine Loading and Releasementioning

confidence: 99%

Hyaluronan Graft Copolymers Bearing Fatty-Acid Residues as Self-Assembling Nanoparticles for Olanzapine Delivery

et al. 2019

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In order to evaluate the potential of a technology platform based on hyaluronan copolymers grafted with propargylated ferulate fluorophores (HA-FA-Pg) in the development of drug delivery systems, the propargyl groups of HA-FA-Pg derivatives were employed with oleic acid (OA) or stearic acid (SA) residues across a biocompatible hexa(ethylene glycol) (HEG) spacer. The designed materials (i.e., HA-FA-HEG-OA or HA-FA-HEG-SA) showed clear-cut aggregation features in an aqueous environment, as confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM), generating nanoaggregate systems. In fact, HA-FA-HEG-OA and HA-FA-HEG-SA derivatives showed the property to create self-assembled cytocompatible nanostructured aggregates in water, thanks to the simultaneous presence of hydrophilic portions in the polymeric backbone, such as hyaluronic acid, and hydrophobic portions in the side chains. Furthermore, the designed materials interact with living cells showing a high degree of cytocompatibility. The potential ability of nanosystems to load pharmacologically active molecules was assessed by the physical entrapment of olanzapine into both polymeric systems. The drug loading evaluation demonstrated that the nanoparticles are able to incorporate a good quantity of olanzapine, as well as improve drug solubility, release profile, and cytocompatibility.

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“…However, OL exhibits very slight solubility in water and suffers from extensive first pass metabolism and, therefore, possesses low bioavailability (40%) after oral administration (Sood et al, 2013). Numerous trials were reported in the literature for improving bioavailability of OL using solid lipid nanoparticles or through formation of solid dispersions with various polymeric carriers (Krishnamoorthy et al, 2009;Harde et al, 2011;Cavallari et al, 2013;Sood et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

In vitro/in vivo evaluation of an optimized fast dissolving oral film containing olanzapine co-amorphous dispersion with selected carboxylic acids

et al. 2016

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Improvement of water solubility, dissolution rate, oral bioavailability, and reduction of first pass metabolism of OL (OL), were the aims of this research. Co-amorphization of OL carboxylic acid dispersions at various molar ratios was carried out using rapid solvent evaporation. Characterization of the dispersions was performed using differential scanning calorimetry (DSC), Fourier transform infrared spectrometry (FTIR), X-ray diffractometry (XRD), and scanning electron microscopy (SEM). Dispersions with highest equilibrium solubility were formulated as fast dissolving oral films. Modeling and optimization of film formation were undertaken using artificial neural networks (ANNs). The results indicated co-amorphization of OL-ascorbic acid through H-bonding. The co-amorphous dispersions at 1:2 molar ratio showed more than 600-fold increase in solubility of OL. The model optimized fast dissolving film prepared from the dispersion was physically and chemically stable, demonstrated short disintegration time (8.5 s), fast dissolution (97% in 10 min) and optimum tensile strength (4.9 N/cm 2 ). The results of in vivo data indicated high bioavailability (144 ng h/mL) and maximum plasma concentration (14.2 ng/mL) compared with the marketed references. Therefore, the optimized co-amorphous OL-ascorbic acid fast dissolving film could be a valuable solution for enhancing the physicochemical and pharmacokinetic properties of OL.

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Design of Olanzapine/Lutrol Solid Dispersions of Improved Stability and Performances

Cited by 24 publications

References 13 publications

Orodispersible Polymer Films with the Poorly Water-Soluble Drug, Olanzapine: Hot-Melt Pneumatic Extrusion for Single-Process 3D Printing

Orodispersible Polymer Films with the Poorly Water-Soluble Drug, Olanzapine: Hot-Melt Pneumatic Extrusion for Single-Process 3D Printing

Hyaluronan Graft Copolymers Bearing Fatty-Acid Residues as Self-Assembling Nanoparticles for Olanzapine Delivery

In vitro/in vivo evaluation of an optimized fast dissolving oral film containing olanzapine co-amorphous dispersion with selected carboxylic acids

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