Nanoporous Silica Entrapped Lipid-Drug Complexes for the Solubilization and Absorption Enhancement of Poorly Soluble Drugs

Shin, Hey-Won; Kim, Joo-Eun; Park, Young-Joon

doi:10.3390/pharmaceutics13010063

Cited by 9 publications

(8 citation statements)

References 59 publications

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“…All data were expressed as mean ± standard deviation and analyzed using Student's t-test to compare the means of the two groups, or analysis of variance (ANOVA) to evaluate the impact of one or more factors, including the formulation, period, and sequence of crossbar layout for administration, on the pharmacokinetic parameters as fixed effects and a random selection effect of subjects nested within the sequence [43]. Statistical significance was set at p < 0.05.…”

Section: Discussionmentioning

confidence: 99%

“…Drug delivery systems are used to improve the solubility and increase the bioavailability of poorly water-soluble drugs [43][44][45][46][47][48][49][50][51][52][53]. Numerous techniques have been developed in recent years to enhance the oral bioavailability of poorly water-soluble drugs, including mesoporous silica, microemulsions [54], self-nano-emulsifying drug delivery systems [55], lyotropic liquid crystalline nanoparticles, and chitosan nanoparticles [56].…”

Section: Introductionmentioning

confidence: 99%

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Formation of Self-Assembled Liquid Crystalline Nanoparticles and Absorption Enhancement of Ω-3s by Phospholipids and Oleic Acids

Jeon

Jin²,

Park

2021

Pharmaceutics

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This study aimed to optimize and evaluate self-assembled liquid crystalline nanoparticles (SALCs) prepared from phospholipids and oleic acid for enhancing the absorption of ω-3s. We explored the structure and optimal formulation of SALCs, which are composed of ω-3 ethyl ester (ω-3 EE), phospholipids, and oleic acid, using a ternary diagram and evaluated the improvement in ω-3 dissolution, permeation, and oral bioavailability. The in vitro dissolution and pharmacokinetics of ω-3 SALCs were compared with those of Omacor soft capsules (as the reference). The shape of the liquid crystal was determined according to the composition of phospholipids, oleic acids, and ω-3s and was found to be in cubic, lamellar, and hexagonal forms. The dissolution rates of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) obtained from ω-3 SALCs were 1.7 to 2.3-fold higher than those of the Omacor soft capsules. Furthermore, a pharmacokinetic study in male beagle dogs revealed that ω-3 SALCs increased the oral bioavailability of ω-3 EE by 2.5-fold for EPA and 3.1-fold for DHA compared with the reference. We found an optimal formulation that spontaneously forms liquid crystal-based nanoparticles, improving the bioavailability of EPA and DHA, not found in the existing literature. Our findings offer insight into the impact of nanoparticle phase on the oral delivery of oil-soluble drugs and provide a novel ω-3 EE formulation that improves the bioavailability of EPA and DHA.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Formation of Self-Assembled Liquid Crystalline Nanoparticles and Absorption Enhancement of Ω-3s by Phospholipids and Oleic Acids

Jeon

Jin²,

Park

2021

Pharmaceutics

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“…After overlapping the contour maps of each response, response surface methods were used to identify the ideal window of the operability design space according to the acceptable range and failure edges with relation to the individual goals [25].…”

Section: Development Of the Design Spacementioning

confidence: 99%

QbD Consideration for Developing a Double-Layered Tablet into a Single-Layered Tablet with Telmisartan and Amlodipine

Kim

Park

2022

Pharmaceutics

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The aim of this study was to develop a single-layered version of commercially available Twynstar® (Telmisartan + Amlodipine) double-layered tablets to improve the dosing convenience. A quality-by-design approach was applied to develop the single-layered version. To evaluate the range and cause of risks for a single-layered tablet in the formulation design research, we used the tools of the risk assessment, initial risk assessment of preliminary hazard analysis and main risk assessment of failure mode and effect analysis to determine the parameters affecting formulation, drug dissolution, and impurities. The critical material attributes were the stabilizer and disintegrant, and the critical process parameters were the wet granulation and tableting process. The optimal range of the design space was determined using the central composite design in the wet granulation and tablet compression processes. The stabilizer, kneading time, and disintegrant of the wet granulation were identified as X values affecting Y values. The compression force and turret speed in the tablet compression were identified as X values affecting Y values. After deciding on the design space with the deduced Y values, the single-layered tablets were formulated, and their dissolution patterns were compared with that of the double-layered tablet. The selected quality-by-design (QbD) approach single-layered tablet formulated using design space were found to be bioequivalent to the Twynstar® double-layered tablets. Hence, the development of single-layered tablets with two API using the QbD approach could improve the medication compliance of patients and could be used as a platform to overcome time-consuming and excessive costs and the technical and commercial limitations related to various multi-layered tablets.

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“…Compressibility index between 10 and 30 indicates good flowability and angle of repose below 40° is acceptable. 59…”

Section: Characterization Of Uncoated F7-smcc and Coated C1-smcc Powders Micrometric Propertiesmentioning

confidence: 99%

“…Uncoated F7-SMCC and coated C1-SMCC showed insignificant difference (P<0.05) in percent drug content of the different quantities of the powder, indicating homogenous distribution of the drug throughout the powder. 59 In vitro Dissolution Study of Uncoated F7-SMCC and Coated C1-SMCC Powders Figure 7 manifests the dissolution profiles of CC from uncoated F7-SMCC and coated C1-SMCC powders compared with free CC, in different gastrointestinal physiological pH values. Different parameters could control the drug release such as the solubility of the drug, the solubility of CS coat, pH of the dissolution medium, and PS of the niosomes.…”

Section: Drug Content Homogeneitymentioning

confidence: 99%

New Peceol™/Span™ 60 Niosomes Coated with Chitosan for Candesartan Cilexetil: Perspective Increase in Absolute Bioavailability in Rats

AbuElfadl¹,

Boughdady²,

Meshali³

2021

IJN

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Purpose: Candesartan cilexetil (CC), a prodrug of candesartan (CDT), is a class II BCS drug that suffers from poor oral bioavailability because of low aqueous solubility, P-gp efflux and first-pass metabolism. The absolute bioavailability reported for CC was only 15% and the methods to increase it remain elusive, thus the aim of our work was to prepare new CCloaded niosomes encompassing, for the first time, glycerol monooleate GMO (Peceol™), as P-gp efflux inhibitor and promoter of lymphatic transport with Span™ 60 as bioenhancer. The prepared niosomes were further coated with chitosan for augmenting the CC oral absorption. Methods: The niosomes were prepared by thin film hydration method through quality by design approach, using two levels of each of three critical process parameters (CPPs), namely, X A (the molar ratio of surfactant mixture to cholesterol) at a ratio of 1:1 or 2:1; X B (the molar ratio of Span™ 60 to Peceol™) at a ratio of 1:1 or 2:1; and X C (the drug amount) at 15 mg or 30 mg. The investigated critical quality attributes (CQAs) were entrapment efficiency percent, particle size, and polydispersity index. The optimized uncoated and chitosan coated formulations were subjected to DSC and stability study. In vitro drug release, biocompatibility with Caco-2 cells and lastly the absolute bioavailability evaluation in rats were assessed. Results: The physical properties of the optimized and stable niosomes were satisfactory. The ingredients were compatible with each other and biocompatible with Caco-2 cells. The synergistic combination of Peceol™ and Span™ 60 probably surmounted the P-gp efflux with an increase in oral absolute bioavailability of niosomes to five times that of CC suspension. Conclusion:The new niosomal formulations of CC containing Peceol™ with Span™ 60 and cholesterol either uncoated or coated with chitosan were a successful paradigm in achieving high oral absolute bioavailability and increased Caco-2 cells biocompatibility.

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Nanoporous Silica Entrapped Lipid-Drug Complexes for the Solubilization and Absorption Enhancement of Poorly Soluble Drugs

Cited by 9 publications

References 59 publications

Formation of Self-Assembled Liquid Crystalline Nanoparticles and Absorption Enhancement of Ω-3s by Phospholipids and Oleic Acids

Formation of Self-Assembled Liquid Crystalline Nanoparticles and Absorption Enhancement of Ω-3s by Phospholipids and Oleic Acids

QbD Consideration for Developing a Double-Layered Tablet into a Single-Layered Tablet with Telmisartan and Amlodipine

New Peceol™/Span™ 60 Niosomes Coated with Chitosan for Candesartan Cilexetil: Perspective Increase in Absolute Bioavailability in Rats

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