Stabilization of the Amorphous Ezetimibe Drug by Confining Its Dimension

Knapik, J.; Wojnarowska, Ż.; Grzybowska, K.; Jurkiewicz, Karolina; Stankiewicz, AI; Paluch, Marian

doi:10.1021/acs.molpharmaceut.5b00903

Cited by 47 publications

(53 citation statements)

References 46 publications

(65 reference statements)

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“…The adsorbents; Aeroperl ® 300 (A300) and Neusilin ® US2 (NUS) were obtained from Evonik industries (Germany) and Fuji Chemical Industry (Japan), respectively. More detailed information, about the chemical nature and particle properties of the adsorbents, are described in Table 5 [54,55,60]. [54] 300 300 Particle Size (µm) [60] 30-40 60-120 Pore Volume (ml/g) * [54] 2.2 4 Peak Pore Size (nm) ** [54] ≈25 ≈800 Predominant Type of Pores [54,55] Mesoporous (2-50nm) Macroporous (>50nm) * based on the mercury intrusion-extrusion technique.…”

Section: Chemicals and Reagentsmentioning

confidence: 99%

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

et al. 2020

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Background: Bioactive oils of natural origin have gained huge interests from health care professionals and patients. Objective: To design a bioactive self-nanoemulsifying drug delivery system (Bio-SNEDDS) comprising curcumin (CUR) and piperine (PP) by incorporating bioactive natural oils in the formulation. Methods: The self-emulsifying properties of apricot, avocado, black seed and Zanthoxylum rhetsa seed oils were screened within various SNEDDS formulations. Each liquid SNEDDS formulation was loaded with both CUR and PP. The optimal liquid SNEDDS were solidified using Aeroperl® and Neusilin® at 1:1 w/w ratio. Liquid and solid SNEDDS were characterized by droplet size analysis, equilibrium solubility, scanning electron microscopy, X-ray powder diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy. In-vitro dissolution studies were performed to evaluate the efficiency of CUR and PP release from solid Bio-SNEDDS. Results: The liquid SNEDDS comprised of black seed oil exhibited excellent self-emulsification performance, low droplet size along with transparent appearance. The inclusion of the cosolvent Transcutol P improved the solubilization capacity of both CUR and PP. The liquid SNEDDS were efficiently solidified using the two adsorbents and presented the drugs within amorphous state. In particular, SNEDDS comprised of black seed oil/Imwitor988/Transcutol P/Cremophor RH40 (20/20/10/50) and when solidified with Neusilin showed enhanced CUR and PP release (up to 60% and 77%, respectively). In addition, this formulation efficiently delivers the highly bioactive black seed oil to the patient. Conclusions: The optimized Bio-SNEDDS comprising black seed oil showed outstanding self-emulsification characteristics along with enhanced CUR/PP dissolution upon solidification.

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Section: Chemicals and Reagentsmentioning

confidence: 99%

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

et al. 2020

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“…Usually, the improvement of an amorphous drug's physical stability by MS is explained by one of two mechanisms: (i) confinement of the API molecules inside the MS pores or (ii) molecular interactions between functional groups of the API molecules and the surface of the stabilizing excipient [28,33,34]. It is worth noting that, in the case of the former mechanism, it is possible to reach even an eternal stabilization effect [35]. Such a situation might occur only when the pore diameter of the employed MS is smaller than the critical crystal nuclei of the API, as well as if all API molecules are incorporated inside the pores.…”

Section: Introductionmentioning

confidence: 99%

Importance of Mesoporous Silica Particle Size in the Stabilization of Amorphous Pharmaceuticals—The Case of Simvastatin

et al. 2020

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In this paper, the role of mesoporous silica (MS) particle size in the stabilization of amorphous simvastatin (SVT) is revealed. For inhibiting recrystallization of the supercooled drug, the two MS materials (Syloid® XDP 3050 and Syloid® 244 FP) were employed. The crystallization tendency of SVT alone and in mixture with the MS materials was investigated by Differential Scanning Calorimetry (DSC) and Broadband Dielectric Spectroscopy (BDS). Neither confinement of the SVT molecules inside the MS pores nor molecular interactions between functional groups of the SVT molecules and the surface of the stabilizing excipient could explain the observed stabilization effect. The stabilization effect might be correlated with diffusion length of the SVT molecules in the MS materials that depended on the particle size. Moreover, MS materials possessing different particle sizes could offer free spaces with different sizes, which might influence crystal growth of SVT. All of these factors must be considered when mesoporous materials are used for stabilizing pharmaceutical glasses.

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“…A general understanding of the T g behavior on confinement is lacking. 60 Neat CNC did not demonstrate any porosity according to the nitrogen adsorption experiments. The lack of porosity in neat CNC indicates that the CNC nanoparticles are in close contact in the spray-dried material which prevents the nitrogen from penetrating into the material.…”

Section: Intraparticle Confinementmentioning

confidence: 84%

“…Knapik et al 60 reported that the T g of ezetimibe loaded into the mesoporous Aeroperl 300 was increased with 0.8 C and increased with 6.7 C when loaded into Neusilin US2 compared with neat amorphous ezetimibe. Furthermore, the T g of glycerol was increased as a function of the pore size when confined in MCM-41.…”

Section: Intraparticle Confinementmentioning

confidence: 99%

Confinement of Amorphous Lactose in Pores Formed Upon Co-Spray Drying With Nanoparticles

Hellrup

Mahlin

2017

Journal of Pharmaceutical Sciences

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This study aims at investigating factors influencing humidity-induced recrystallization of amorphous lactose, produced by co-spray drying with particles of cellulose nanocrystals or sodium montmorillonite. In particular, the focus is on how the nanoparticle shape and surface properties influence the nanometer to micrometer length scale nanofiller arrangement in the nanocomposites and how the arrangements influence the mechanisms involved in the inhibition of the amorphous to crystalline transition. The nanocomposites were produced by co-spray drying. Solid-state transformations were analyzed at 60%-94% relative humidity using X-ray powder diffraction, microcalorimetry, and light microscopy. The recrystallization rate constant for the lactose/cellulose nanocrystals and lactose/sodium montmorillonite nanocomposites was lowered at nanofiller contents higher than 60% and was stable for months at 80% nanofiller. The most likely explanation to these results is spontaneous formations of mesoporous particle networks that the lactose is confined upon co-spray drying at high filler content. Compartmentalization and rigidification of the amorphous lactose proved to be less important mechanisms involved in the stabilization of lactose in the nanocomposites.

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Stabilization of the Amorphous Ezetimibe Drug by Confining Its Dimension

Cited by 47 publications

References 46 publications

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

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

Importance of Mesoporous Silica Particle Size in the Stabilization of Amorphous Pharmaceuticals—The Case of Simvastatin

Confinement of Amorphous Lactose in Pores Formed Upon Co-Spray Drying With Nanoparticles

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