Ordered mesoporous silica to enhance the bioavailability of poorly water-soluble drugs: Proof of concept in man

Bukara, Katarina; Schueller, Laurent; Rosier, Jan; Martens, Mark A.; Daems, Tinne; Verheyden, Loes; Eelen, Siemon; Speybroeck, Michiel Van; Libanati, Cristian; Martens, Jürgen; Mooter, Guy Van den; Frérart, Françoise; Jolling, Koen; Gieter, M. De; Bugarski, Branko; Kiekens, Filip

doi:10.1016/j.ejpb.2016.08.020

Cited by 90 publications

(63 citation statements)

References 13 publications

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“…This is because they might very effectively stabilize amorphous APIs and 2 of 21 they can also very effectively enhance their bioavailability [29]. A great example of a drug in which bioavailability has been effectively enhanced after preparation MS based formulation is fenofibrate [30]. In choosing an appropriate MS for drug formulation, it is important to check its degradability.…”

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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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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“…All three compounds represent Biopharmaceutical Classification System (BCS) II APIs (Amidon, 1995). This low solubility, coupled with the incomplete dissolution of the drugs in biorelevant media (Figure 2) (Bukara, 2016). In that study, which compared fenofibrate loaded silica with the commercially available micronized Lipanthyl® formulation, a 77% increase in Cmax, a reduced tmax and a % increase AUC0-24h/dose for fenofibrate loaded silica was observed, demonstrating that loading this API onto mesoporous silica can increase both the rate and extent of absorption.…”

Section: The Importance Of Enabling Formulationsmentioning

confidence: 82%

Calculation of drug-polymer mixing enthalpy as a new screening method of precipitation inhibitors for supersaturating pharmaceutical formulations

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Kuentz

et al. 2019

European Journal of Pharmaceutical Sciences

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Supersaturating formulations are widely used to improve the oral bioavailability of poorly soluble drugs. However, supersaturated solutions are thermodynamically unstable and such formulations often must include a precipitation inhibitor (PI) to sustain the increased concentrations to ensure that sufficient absorption will take place from the gastrointestinal tract. Recent advances in understanding the importance of drug-polymer interaction for successful precipitation inhibition have been encouraging. However, there still exists a gap in how this newfound understanding can be applied to improve the efficiency of PI screening and selection, which is still largely carried out with trial and error-based approaches. The aim of this study was to demonstrate how drugpolymer mixing enthalpy, calculated with the Conductor like Screening Model for Real Solvents (COSMO-RS), can be used as a parameter to select the most efficient precipitation inhibitors, and thus realise the most successful supersaturating formulations. This approach was tested for three different Biopharmaceutical Classification System (BCS) II compounds: dipyridamole, fenofibrate and glibenclamide, formulated with the supersaturating formulation, mesoporous silica. For all three compounds, precipitation was evident in mesoporous silica formulations without a precipitation inhibitor. Of the nine precipitation inhibitors studied, there was a strong positive correlation between the drug-polymer mixing enthalpy and the overall formulation performance, as measured by the area under the concentration-time curve in in vitro dissolution experiments. The data suggest that a rank-order based approach using calculated drug-polymer mixing enthalpy can be reliably used to select precipitation inhibitors for a more focused screening. Such an approach improves efficiency of precipitation inhibitor selection, whilst also improving the likelihood that the most optimal formulation will be realised.

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“…However, it should be mentioned that silica is "generally recognized as safe" by the US Food and Drug Administration (FDA), and it is often used as excipient in drug formulations and as dietary supplement [18,19]. In this sense, the administration of fenofibrate-loaded ordered mesoporous silica materials in men was found to be safe, and the doses were well tolerated by the patients [20]. In addition, small silica nanoparticles (c-dots, 7 nm) for imaging purposes were approved by the US FDA for a human clinical trial, demonstrating that they were well tolerated by the patients and accumulated in the tumor site [21].…”

Section: Introductionmentioning

confidence: 99%

Mesoporous Silica Nanoparticles for the Treatment of Complex Bone Diseases: Bone Cancer, Bone Infection and Osteoporosis

2020

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Bone diseases, such as bone cancer, bone infection and osteoporosis, constitute a major issue for modern societies as a consequence of their progressive ageing. Even though these pathologies can be currently treated in the clinic, some of those treatments present drawbacks that may lead to severe complications. For instance, chemotherapy lacks great tumor tissue selectivity, affecting healthy and diseased tissues. In addition, the inappropriate use of antimicrobials is leading to the appearance of drug-resistant bacteria and persistent biofilms, rendering current antibiotics useless. Furthermore, current antiosteoporotic treatments present many side effects as a consequence of their poor bioavailability and the need to use higher doses. In view of the existing evidence, the encapsulation and selective delivery to the diseased tissues of the different therapeutic compounds seem highly convenient. In this sense, silica-based mesoporous nanoparticles offer great loading capacity within their pores, the possibility of modifying the surface to target the particles to the malignant areas and great biocompatibility. This manuscript is intended to be a comprehensive review of the available literature on complex bone diseases treated with silica-based mesoporous nanoparticles—the further development of which and eventual translation into the clinic could bring significant benefits for our future society.

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Ordered mesoporous silica to enhance the bioavailability of poorly water-soluble drugs: Proof of concept in man

Cited by 90 publications

References 13 publications

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

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

Calculation of drug-polymer mixing enthalpy as a new screening method of precipitation inhibitors for supersaturating pharmaceutical formulations

Mesoporous Silica Nanoparticles for the Treatment of Complex Bone Diseases: Bone Cancer, Bone Infection and Osteoporosis

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