Drug loading to mesoporous silica carriers by solvent evaporation: A comparative study of amorphization capacity and release kinetics

Šoltys, Marek; Zůza, David; Boleslavská, Tereza; Akhlasová, Sarah Machač; Balouch, Martin; Kovačík, Pavel; Beránek, Josef; Škalko‐Basnet, Nataša; Flaten, Gøril Eide; Štěpánek, František

doi:10.1016/j.ijpharm.2021.120982

Cited by 13 publications

(9 citation statements)

References 39 publications

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“…The incorporation of a drug into mesoporous silica (MPS) is a promising strategy to stabilize its amorphous form [11]. MPS is small enough carrier that is thermodynamically more favorable for the drug to remain in a disordered rather than crystalline state inside the pore [12]. Two responsible mechanisms explain the inhibition of drug crystallization, which include (i) the molecular interaction between functional groups of the drug molecules and the surface of MPS, such as hydrogen bonding and (ii) the nanoconfinement effect of MPS, leading to the suppression of nucleation and crystal growth of the drug as the pore size of MPS is smaller than the critical crystalline nuclei [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

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Characterization of Drugs with Good Glass Formers in Loaded-Mesoporous Silica and Its Theoretical Value Relevance with Mesopores Surface and Pore-Filling Capacity

Budiman

Aulifa

2022

Pharmaceuticals

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The incorporation of a drug into mesoporous silica (MPS) is a promising strategy to stabilize its amorphous form. However, the drug within MPS has shown incomplete release, despite a supersaturated solution being generated. This indicates the determination of maximum drug loading in MPS below what is experimentally necessary to maximize the drug doses in the system. Therefore, this study aimed to characterize the drugs with good glass former loaded-mesoporous silica, determine the maximum drug loading, and compare its theoretical value relevance to monolayer covering the mesoporous (MCM) surface, as well as pore-filling capacity (PFC). Solvent evaporation and melt methods were used to load each drug into MPS. In addition, the glass transition of ritonavir (RTV) and cyclosporine A (CYP), as well as the melting peak of indomethacin (IDM) and saccharin (SAC) in mesoporous silica, were not discovered in the modulated differential scanning calorimetry (MDSC) curve, demonstrating that each drug was successfully incorporated into the mesopores. The amorphization of RTV-loaded MPS (RTV/MPS), CYP-loaded MPS (CYP/MPS), and IDM-loaded MPS (IDM/MPS) were confirmed as a halo pattern in powder X-ray diffraction measurements and a single glass transition event in the MDSC curve. Additionally, the good glass formers, nanoconfinement effect of MPS and silica surface interaction contributed to the amorphization of RTV, CYP and IDM within MPS. Meanwhile, the crystallization of SAC was observed in SAC-loaded MPS (SAC/MPS) due to its weak silica surface interaction and high recrystallization tendency. The maximum loading amount of RTV/MPS was experimentally close to the theoretical amount of MCM, showing monomolecular adsorption of RTV on the silica surface. On the other hand, the maximum loading amount of CYP/MPS and IDM/MPS was experimentally lower than the theoretical amount of MCM due to the lack of surface interaction. However, neither CYP or IDM occupied the entire silica surface, even though some drugs were adsorbed on the MPS surface. Moreover, the maximum loading amount of SAC/MPS was experimentally close to the theoretical amount of PFC, suggesting the multilayers of SAC within the MPS. Therefore, this study demonstrates that the characterization of drugs within MPS, such as molecular size and interaction of drug-silica surface, affects the loading efficiency of drugs within MPS that influence its relevance with the theoretical value of drugs.

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Section: Introductionmentioning

confidence: 99%

“…However, the possibility of recrystallization on the surface of MPS needs to be considered in the case of exceeding the pore capacity. Therefore, choosing a loading method is crucial for high drug loading into MPS [12].…”

Section: Introductionmentioning

confidence: 99%

Characterization of Drugs with Good Glass Formers in Loaded-Mesoporous Silica and Its Theoretical Value Relevance with Mesopores Surface and Pore-Filling Capacity

Budiman

Aulifa

2022

Pharmaceuticals

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“…The mesoporous structure enabled the stabilization of the amorphous drug due to the spatial confinement effect, while the presence of macropores enabled the rapid flow of the molten drug through the particles. The possibility of incorporation of seven APIs of different physicochemical properties into silica carriers by solvent evaporation was demonstrated by Šoltys et al The APIs incorporated in the mesoporous materials remained in an amorphous state, while loading into hierarchical meso-/macroporous silicas resulted in loading level-dependent crystallization of the compounds . Recently, our group presented novel hierarchical porous monoliths, which thanks to the high accessibility and sorption capacity, allowed us to control the release of APIs adsorbed in its pores .…”

Section: Introductionmentioning

confidence: 99%

“…The possibility of incorporation of seven APIs of different physicochemical properties into silica carriers by solvent evaporation was demonstrated by Šoltys et al 30 The APIs incorporated in the mesoporous materials remained in an amorphous state, while loading into hierarchical meso-/macroporous silicas resulted in loading level-dependent crystallization of the compounds. 30 Recently, our group presented novel hierarchical porous monoliths, which thanks to the high accessibility and sorption capacity, allowed us to control the release of APIs adsorbed in its pores. 31 Careful control of the synthetic conditions allows tailoring the size of both macro- and mesopores, enabling the adjustment of the properties of the carrier to drug molecules or specific release profiles.…”

Section: Introductionmentioning

confidence: 99%

Hierarchical Macro-Mesoporous Silica Monolithic Tablets as a Novel Dose–Structure-Dependent Delivery System for the Release of Confined Dexketoprofen

et al. 2022

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This study reports the application of hierarchical porous monoliths as carriers for controlled and dose-adjustable release of model pharmaceutical (dexketoprofen, DEX). The synthesis and detailed characterization of the hierarchical porous scaffolds are provided before and after the adsorption of three doses of DEX—a widely used nonsteroidal anti-inflammatory drug. The drug incorporated in the mesopores of silica was stabilized in an amorphous state, while the presence of macropores provided sufficient space for drug crystallization as we demonstrated via a combination of powder X-ray diffraction, differential scanning calorimetry, and imaging techniques (scanning electron microscopy and EDX analysis). Drug release from silica matrices was tested, and a mechanistic model of this release based on the Fick diffusion equation was proposed. The hierarchical structure of the carrier, due to the presence of micrometric macropores and nanometric mesopores, turned out to be critical for the control of the drug phase and drug release from the monoliths. It was found that at low drug content, the presence of an amorphous component in the pores promoted the rapid release of the drug, while at higher drug contents, the presence of macropores favored the crystallization of DEX, which naturally slowed down its release. Both the hierarchical porous structure and the control of the drug phase (amorphous and/or crystalline) were proven important for adjustable (fast or prolonged) release kinetics, desirable for effective pharmacotherapy and patient compliance. Therefore, the developed materials may serve as a versatile formulation platform for the smart manipulation of drug release kinetics.

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“…Dissolved drugs in appropriate solvents stabilized by polymers and surfactants will fill the mesoporous pore. The evaporation of the solvent promotes the formation of NCs [20]. It features low thermodynamic stability due to its high Gibbs free energy; thus, it requires stabilization.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Nanocrystal Incorporated into Mesoporous Material: Rational Design and Screening through Quality-by-Design Approach

et al. 2022

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Bioflavonoids from grape seeds feature powerful antioxidant and immunostimulant activities, but they present problems related to solubility and bioavailability. Nanocrystal (NC) incorporated into a mesoporous carrier is a promising strategy to address these issues. However, the preparation of this formulation involves the selection of factors affecting its critical quality attributes. Hence, this study aimed to develop an NC formulation incorporating resveratrol into a soluble mesoporous carrier based on rational screening design using a systematic and continuous development process, the quality-by-design paradigm. A mesoporous soluble carrier was prepared by spray-drying mannitol and ammonium carbonate. The NC was obtained by introducing the evaporated solvent containing a drug/polymer/surfactant and mesoporous carrier to the medium. A 26−2 fractional factorial design (FFD) approach was carried out in the screening process to understand the main effect factors. The type and concentration of polymer and surfactant, resveratrol loading, and solvent were determined on the NC characteristics. The results indicated that drug loading, particle size, and solubility were mainly affected by RSV loading, PEG concentration, and Kolliphor EL concentration. The polymer contributed dominantly to reducing the particle size and enhancing solubility in this screening design. The presence of surfactants in this system made it possible to prolong the supersaturation process. According to the 26−2 FFD, the factors selected to be further developed using a statistical technique according to the quality-by design-approach, Box Behnken Design, were Kolliphor EL, PEG400, and RSV loading.

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Drug loading to mesoporous silica carriers by solvent evaporation: A comparative study of amorphization capacity and release kinetics

Cited by 13 publications

References 39 publications

Characterization of Drugs with Good Glass Formers in Loaded-Mesoporous Silica and Its Theoretical Value Relevance with Mesopores Surface and Pore-Filling Capacity

Characterization of Drugs with Good Glass Formers in Loaded-Mesoporous Silica and Its Theoretical Value Relevance with Mesopores Surface and Pore-Filling Capacity

Hierarchical Macro-Mesoporous Silica Monolithic Tablets as a Novel Dose–Structure-Dependent Delivery System for the Release of Confined Dexketoprofen

Resveratrol Nanocrystal Incorporated into Mesoporous Material: Rational Design and Screening through Quality-by-Design Approach

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