Development of a Hydrophobicity-Controlled Delivery System Containing Levodopa Methyl Ester Hydrochloride Loaded into a Mesoporous Silica

Background: The drug release of antiparkinsonian drugs is an important issue during the formulation process because proper release kinetics can help to reduce the off periods of Parkinson’s disease. A 2-factor, 3-level (32) full-factorial design was conducted to evaluate statistically the influence of the hydrophobicity of mesoporous silica on drug release. Methods: Hydrophobization was evaluated by different methods, such as contact angle measurement, infrared spectroscopy and charge titration. After loading the drug (levodopa methyl ester hydrochloride, melevodopa hydrochloride, LDME) into the mesopores, drug content, particle size, specific surface area and homogeneity of the products were also analyzed. The amorphous state of LDME was verified by X-ray diffractometry and differential scanning calorimetry. Results: Drug release was characterized by a model-independent method using the so-called initial release rate parameter, as detailed in the article. The adaptability of this method was verified; the model fitted closely to the actual release results according to the similarity factor, independently of the release kinetics. Conclusions: The API was successfully loaded into the silica, resulting in a reduced surface area. The release studies indicated that the release rate significantly decreased (p < 0.05) with increasing hydrophobicity. The products with controlled release can reduce the off period frequency.

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In Vitro Evaluation of a Peptide-Mesoporous Silica Nanoparticle Drug Release System against HIV-1

Inorganics ◽

10.3390/inorganics8070042 ◽

2020 ◽

Vol 8 (7) ◽

pp. 42 ◽

Cited By ~ 1

Author(s):

Katharina Braun ◽

Christina M. Stürzel ◽

Frank Kirchhoff ◽

Mika Lindén

Keyword(s):

Drug Release ◽

Mesoporous Silica ◽

Release Rate ◽

Serum Proteins ◽

Release Kinetics ◽

Drug Loading ◽

Active Form ◽

Equilibrium Concentration ◽

Hiv 1

It has been shown that the optimized VIR-576 derivative of the natural HIV-1 entry inhibitor targeting the viral gp41 fusion peptide is safe and effective in infected individuals. However, high doses of this peptide were required, and stability, as well as delivery, must be improved for clinical application. Here, we examined the loading and release of VIR-576 into/from mesoporous silica nanoparticles (MSNs) in vitro. We found that a moderately high peptide loading of 11.5 wt % could be achieved by adsorption from PBS buffer (pH 7.2), i.e., under mild, fully peptide-compatible conditions. The release rate of peptide into the same buffer was slow and the equilibrium concentration as indicated by the adsorption isotherm could not be reached even within 50 h at the particle concentrations studied. However, a faster release was observed at lower particle concentrations, indicating that partial particle dissolution had a positive influence on peptide release. To determine the antiviral activity of VIR-576-loaded MSNs, TZM-bl indicator cells were exposed to HIV-1 and the infection rates were followed as a function of time and VIR-576 concentration. The inhibitory activity observed for VIR-576 released from the MSNs was virtually identical to that of free VIR-576 at the 48 h time point, indicating that (a) VIR-576 was released in an active form from the MSNs, and (b) the release rate in the presence of serum proteins was clearly higher than that observed under protein-free conditions. These observations are discussed based on competitive peptide/protein adsorption, as well as potential influences of serum proteins on the dissolution-reprecipitation of silica under conditions where the total silica concentration is above the saturation level for dissolved silica. Our results highlight the need for studying drug release kinetics in the presence of serum proteins, in order to allow for a better extrapolation of in vitro data to in vivo conditions. Furthermore, due to the high peptide loadings that can be achieved using MSNs as carriers, such a formulation appears promising for local release applications. For systemic administration, however, peptides with a higher potency would be needed, due to their high molar masses limiting the drug loading in terms of moles per gram carrier.

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Silica-Alginate Beads for Intestinal Ketoprofen Delivery

Revista de Chimie ◽

10.37358/rc.18.12.6761 ◽

2019 ◽

Vol 69 (12) ◽

pp. 3416-3422

Author(s):

Marilena Petrescu ◽

Raul Augustin Mitran ◽

Cristian Matei ◽

Marius Radulescu ◽

Daniela Berger

Keyword(s):

Side Effects ◽

Drug Release ◽

Mesoporous Silica ◽

Release Rate ◽

Release Kinetics ◽

Alginate Beads ◽

Drug Release Rate ◽

Silica Materials ◽

Mesocellular Foam Silica ◽

Mcm 41

Herein, studies on ketoprofen delivery systems based on silica-alginate beads developed for the drug intestinal release for reducing its side effects were reported. The influence of surface properties, pore size and geometry of mesoporous silica carriers on the ketoprofen release kinetics was studied by using pristine and 3-aminopropyl functionalized MCM 41 (Mobile Composition of Matter) and MCF (mesocellular foam silica) materials. The ketoprofen loaded mesoporous silica coated with alginate is a pH-triggered system able to slow down the drug release rate in the targeted environment.

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Hydrophilic and Hydrophobic Mesoporous Silica Derived from Rice Husk Ash as a Potential Drug Carrier

10.20944/preprints201806.0264.v1 ◽

2018 ◽

Author(s):

Supakij Suttiruengwong ◽

Metta Chareonpanich ◽

Sommai Pivsa-Art

Keyword(s):

Mesoporous Silica ◽

Surface Area ◽

Rice Husk ◽

Release Rate ◽

Pore Diameter ◽

Rice Husk Ash ◽

Release Kinetics ◽

Drug Carrier ◽

Bet Surface Area ◽

Hydrophobic Nature

This work describes the preparation of mesoporous silica by the green reaction of rice husk ash (RHA) with glycerol, followed by the modification and the potential use as a drug carrier. The reaction was carried out at 215 °C for 2 h. The solution was further hydrolyzed with deionized water and aged for various times (24, 48, 120, 360, 528 and 672 h) before calcinations at 500 oC for 24 h. Further treatment of prepared mesoporous silica was performed using trimethylmethoxysilane (TMMS) to obtain hydrophobic Mesoporous silica. For all synthesized silica, silica contents were as high as 95%wt, whereas organic residues were less than 3%wt. RHA-glycerol showed the highest specific surface area with smallest pore diameter (205.70 m2/g, 7.46 nm) when aged for 48 h. The optimal hydrolysis-ageing period of 120 h resulted in 500.7 m2/g BET surface area, 0.655 cm3/g pore volume and 5.23 nm pore diameter. The surface modification of RHA-glycerol was succeeded through the reaction with TMMS as confirmed by FTIR. Ibuprofen was selected as a model drug for the adsorption experiments. The adsorption under supercritical CO2 was carried out at isothermal temperature of 40 ˚C and 100 bar, % ibuprofen loading of TMMS modified mesoporous silica (TMMS-g-MS) was 6 times less than mesoporous silica aged for 24 h (MS-24h) due to the hydrophobic nature of modified mesoporous silica, not surface and pore characteristics. The release kinetics of ibuprofen-loaded mesoporous silicas were also investigated in vitro. The release rate of ibuprofen-loaded MS-24h was much faster than that of ibuprofen-loaded TMMS-g-MS, but comparable to the crystalline ibuprofen. The slower release rate was attributed to the diffusion control and the stability of hydrophobic nature of modified silica. This would allow the design for the controlled release drug delivery system.

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Cefdinir Inclusion in Mesoporous Silica as Effective Dissolution Enhancer with Improved Physical Stability

Journal of Pharmacy and Nutrition Sciences ◽

10.29169/1927-5951.2021.11.10 ◽

2021 ◽

Vol 11 ◽

pp. 73-86

Author(s):

Raghad Al Nuss ◽

Hind El Zein

Keyword(s):

Drug Release ◽

Mesoporous Silica ◽

Release Kinetics ◽

Physical Stability ◽

Amorphous State ◽

Weibull Model ◽

Drug Dissolution ◽

Scanning Calorimetry ◽

Immersion Method ◽

Amorphous Form

Objective: The objective of this research was to enhance the physical stability and the dissolution rate of cefdinir, a BCS class IV drug, characterized by low and variable bioavailability due to both its low solubility and low permeability. Methods: Cefdinir was loaded into the mesoporous silica (SBA-15), by using the solvent immersion method starting from different organic solvents. And then formula (F3), which exhibited the highest loading percentage, was selected to study its drug release in media with different pH (1.2, 4.5, and 6.8), and has been fully characterized by using: Fourier Transform Infrared Spectroscopy (FT-IR) Spectroscopy, Differential Scanning Calorimetry, Powder X-ray Diffraction, and has been subjected to accelerated stability tests using different temperatures and relative humidity. Drug release kinetics were studied by using the following models: Probit, Gompertz, Weibull, and Logistic. Results: The results showed a remarkable dissolution improvement of cefdinir from the loaded silica in comparison to the crystalline drug at the different studied media. Drug release behaviors were well simulated by the Weibull model for F3 in all studied media and for pure Cefdinir in phosphate buffer only, and by the Gompertz function for pure Cefdinir in HCl buffer and Acetate buffer. FTIR results showed hydrogen bonds formed between the drug and silica, DSC and PXRD results revealed the transformation of cefdinir into an amorphous form upon adsorption. Stability studies under different conditions revealed the ability of mesoporous silica to maintain the amorphous state of the drug, which has been formed upon adsorption, and to prevent re-organization in the crystal nucleus of the drug molecules. Conclusion: Thus, loading cefdinir onto mesoporous silica can be used as a promising method to enhance drug dissolution, and maintain the physical stability of its amorphous form.

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Mesoporous Silica Molecular Sieve based Nanocarriers: Transpiring Drug Dissolution Research

Current Pharmaceutical Design ◽

10.2174/1381612822666161026162005 ◽

2017 ◽

Vol 23 (3) ◽

pp. 467-480 ◽

Cited By ~ 8

Author(s):

Satyanarayan Pattnaik ◽

Kamla Pathak

Keyword(s):

Drug Release ◽

Mesoporous Silica ◽

Molecular Sieves ◽

Release Kinetics ◽

Drug Loading ◽

Scale Up ◽

Water Soluble ◽

Drug Dissolution ◽

Water Soluble Drugs ◽

Loading Methods

Background: Improvement of oral bioavailability through enhancement of dissolution for poorly soluble drugs has been a very promising approach. Recently, mesoporous silica based molecular sieves have demonstrated excellent properties to enhance the dissolution velocity of poorly water-soluble drugs. Description: Current research in this area is focused on investigating the factors influencing the drug release from these carriers, the kinetics of drug release and manufacturing approaches to scale-up production for commercial manufacture. Conclusion: This comprehensive review provides an overview of different methods adopted for synthesis of mesoporous materials, influence of processing factors on properties of these materials and drug loading methods. The drug release kinetics from mesoporous silica systems, the manufacturability and stability of these formulations are reviewed. Finally, the safety and biocompatibility issues related to these silica based materials are discussed.

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