Mechanistic insight into the dramatic improvement of probucol dissolution in neutral solutions by solid dispersion in Eudragit E PO with saccharin

Higashi, Kenjirou; Seo, Atsunori; Egami, Kiichi; Otsuka, Naoto; Limwikrant, Waree; Yamamoto, Keiji; Moribe, Kunikazu

doi:10.1111/jphp.12469

Cited by 29 publications

(25 citation statements)

References 44 publications

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“…The surface activity of EUD-E was also affected by pH and ionic strength. 56) It was hypothesized that the surfactant function of E-SD, which resulted in the formation of a micelle-like structure, was related to reprecipitation inhibition. Fluorescence measurement using pyrene as a probe confirmed that E-SD formed micelle-like structures.…”

Section: Interaction Between Drug and Modified Eud-e In Aqueous Solutionmentioning

confidence: 99%

Intermolecular Interactions between Drugs and Aminoalkyl Methacrylate Copolymer in Solution to Enhance the Concentration of Poorly Water-Soluble Drugs

Higashi

Ueda

Moribe

2019

CHEMICAL & PHARMACEUTICAL BULLETIN

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An aminoalkyl methacrylate copolymer, Eudragit ® E (EUD-E), has gained tremendous attention as a solid dispersion carrier because it efficiently stabilizes drugs in the amorphous state. Furthermore, EUD-E remarkably enhances drug dissolution in water. This review focuses on the interaction between drugs and EUD-E in solution, which contributes to the enhancement of drug concentration. Studies examining interactions between acidic drugs and EUD-E in organic solvents have revealed that the interaction occurs predominantly by electrostatic interaction, including hydrogen bonding and dipolar interactions. Other studies on interactions in aqueous solution found evidence for strong electrostatic interactions between acidic drugs and EUD-E in ion exchange experiments. 1 H-NMR studies using high-resolution magic-angle spinning, nuclear Overhauser effect spectroscopy, diffusion, and relaxation time measurements successfully identified the interaction site and strength in aqueous solution. Hydrophobic and ionic interactions occurred between drugs and EUD-E. The conformation of EUD-E, which was affected by the ionic strength and pH of the aqueous media, also influenced the interaction. The knowledge discussed in this review will be helpful in designing solid dispersion formulations with EUD-E, which will efficiently enhance drug concentration and subsequent absorption into the body.

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Section: Interaction Between Drug and Modified Eud-e In Aqueous Solutionmentioning

confidence: 99%

Intermolecular Interactions between Drugs and Aminoalkyl Methacrylate Copolymer in Solution to Enhance the Concentration of Poorly Water-Soluble Drugs

Higashi

Ueda

Moribe

2019

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…As suitable pharmaceutical polymers for the development of ASDs are limited, research has focused on the development of modified polyelectrolyte matrices combining the already used polymers with small molecular additives [ 125 , 126 ]. From this point of view, ternary solid dispersions of probucol, Eudragit EPO, and saccharin were formed by cryogenic grinding.…”

Section: Modified Polyelectrolyte Matricesmentioning

confidence: 99%

“…Electrostatic interactions between the amide group of saccharin and the tertiary amino group of the polymer were reported, while the preservation of the amorphous state was attributed to the hydrophobic interactions between the drug and Eudragit EPO. In addition, the dissolution profile of probucol in neutral solutions was remarkably enhanced due to these intermolecular interactions, in comparison to the binary mixtures without saccharin [ 125 ].…”

Section: Modified Polyelectrolyte Matricesmentioning

confidence: 99%

Polyelectrolyte Matrices in the Modulation of Intermolecular Electrostatic Interactions for Amorphous Solid Dispersions: A Comprehensive Review

2021

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Polyelectrolyte polymers have been widely used in the pharmaceutical field as excipients to facilitate various drug delivery systems. Polyelectrolytes have been used to modulate the electrostatic environment and enhance favorable interactions between the drug and the polymer in amorphous solid dispersions (ASDs) prepared mainly by hot-melt extrusion. Polyelectrolytes have been used alone, or in combination with nonionic polymers as interpolyelectrolyte complexes, or after the addition of small molecular additives. They were found to enhance physical stability by favoring stabilizing intermolecular interactions, as well as to exert an antiplasticizing effect. Moreover, they not only enhance drug dissolution, but they have also been used for maintaining supersaturation, especially in the case of weakly basic drugs that tend to precipitate in the intestine. Additional uses include controlled and/or targeted drug release with enhanced physical stability and ease of preparation via novel continuous processes. Polyelectrolyte matrices, used along with scalable manufacturing methods in accordance with green chemistry principles, emerge as an attractive viable alternative for the preparation of ASDs with improved physical stability and biopharmaceutic performance.

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“…It has been used as a taste-masking agent (Taki et al, 2017) and provides a glossy and slippery easy-to-swallow finishing. Its use is well established for pharmaceutical purposes as a solubility enhancer (Higashi et al, 2016;Saal et al, 2017Saal et al, , 2018, stability enhancer (Ochi et al, 2016) and in the manufacturing of immediate release dosage forms (Qiao et al, 2010;Sadia et al, 2016;Yang et al, 2015). Its compatibility with hot melt extrusion has also been previously demonstrated (Ashour et al, 2016;Li et al, 2016a;Li et al, 2016b).…”

Section: Introductionmentioning

confidence: 99%

On demand manufacturing of patient-specific liquid capsules via co-ordinated 3D printing and liquid dispensing

Okwuosa

Soares

Gollwitzer

et al. 2018

European Journal of Pharmaceutical Sciences

113

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A method for the production of liquid capsules with the potential of modifying drug dose and release is presented. For the first time, the co-ordinated use of fused deposition modelling (FDM), 3D printing and liquid dispensing to fabricate individualised dosage form on demand in a fully automated fashion has been demonstrated. Polymethacrylate shells (Eudragit EPO and RL) for immediate and extended release were fabricated using FDM 3D printing and simultaneously filled using a computer-controlled liquid dispenser loaded with model drug solution (theophylline) or suspension (dipyridamole). The impact of printing modes: simultaneous shell printing and filling (single-phase) or sequential 3D printing of shell bottom, filling and shell cap (multi-phase), nozzle size, syringe volume, and shell structure has been reported. The use of shell thickness of 1.6 mm, and concentric architecture allowed successful containment of liquid core whilst maintaining the release properties of the 3D printed liquid capsule. The linear relationship between the theoretical and the actual volumes from the dispenser reflected its potential for accurate dosing (R = 0.9985). Modifying the shell thickness of Eudragit RL capsule allowed a controlled extended drug release without the need for formulation change. Owing to its low cost and versatility, this approach can be adapted to wide spectrum of liquid formulations such as small and large molecule solutions and obviate the need for compatibility with the high temperature of FDM 3D printing process. In a clinical setting, health care staff will be able to instantly manufacture in small volumes liquid capsules with individualised dose contents and release pattern in response to specific patient's needs.

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Mechanistic insight into the dramatic improvement of probucol dissolution in neutral solutions by solid dispersion in Eudragit E PO with saccharin

Abstract: Preparation of ternary solid dispersion is a potential method of improving drug solubility and absorption.

Cited by 29 publications

References 44 publications

Intermolecular Interactions between Drugs and Aminoalkyl Methacrylate Copolymer in Solution to Enhance the Concentration of Poorly Water-Soluble Drugs

Intermolecular Interactions between Drugs and Aminoalkyl Methacrylate Copolymer in Solution to Enhance the Concentration of Poorly Water-Soluble Drugs

Polyelectrolyte Matrices in the Modulation of Intermolecular Electrostatic Interactions for Amorphous Solid Dispersions: A Comprehensive Review

On demand manufacturing of patient-specific liquid capsules via co-ordinated 3D printing and liquid dispensing

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