Qualitative and Quantitative Characterization of Composition Heterogeneity on the Surface of Spray Dried Amorphous Solid Dispersion Particles by an Advanced Surface Analysis Platform with High Surface Sensitivity and Superior Spatial Resolution

Advancement in the discovery of drugs has led to many highly lipophilic compounds with very low water solubility. Amorphous solid dispersion is one of the emerging technologies to increase the solubility of these drugs. The stability of these systems is critical since the high energy system tends to recrystallize, which negates the benefits of these systems. In this paper, we are evaluating the use of colloidal silicon dioxide as a potential stabilizer to stabilize the amorphous solid dispersions. Two types of colloidal silicon dioxide are used: porous colloidal silicon dioxide -Syloid 244 Fp and nonporous fumed silica – Aerosil 200. These silicon dioxides have a high surface area. Two methods of incorporation are used to incorporate silicon dioxide into the solid dispersion. The spray drying method is used to make amorphous solid dispersion. It was found that porous silicon dioxide is better to increase stability as well as increasing dissolution rate and % release of the drug. The addition of silicon dioxide internally to the dispersion increases the dissolution rate, and the addition of silicon dioxide externally increases the stability of the solid dispersion. Keywords: colloidal silicon dioxide, stabilizer, amorphous solid dispersion, low water solubility

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Physicochemical and Pharmacokinetic Characterization of Amorphous Solid Dispersion of Tranilast with Enhanced Solubility in Gastric Fluid and Improved Oral Bioavailability

Drug Metabolism and Pharmacokinetics ◽

10.2133/dmpk.dmpk-11-rg-101 ◽

2012 ◽

Vol 27 (4) ◽

pp. 379-387 ◽

Cited By ~ 29

Author(s):

Satomi Onoue ◽

Yoshiki Kojo ◽

Yosuke Aoki ◽

Yohei Kawabata ◽

Yukinori Yamauchi ◽

...

Keyword(s):

Solid Dispersion ◽

Oral Bioavailability ◽

Amorphous Solid ◽

Gastric Fluid ◽

Amorphous Solid Dispersion ◽

Enhanced Solubility

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Phase behavior, intermolecular interaction, and solid state characterization of amorphous solid dispersion of Febuxostat

Pharmaceutical Development and Technology ◽

10.3109/10837450.2016.1138130 ◽

2016 ◽

Vol 22 (1) ◽

pp. 45-57 ◽

Cited By ~ 10

Author(s):

Ashwini Kini ◽

Sarsvatkumar B. Patel

Keyword(s):

Solid State ◽

Phase Behavior ◽

Intermolecular Interaction ◽

Solid Dispersion ◽

Amorphous Solid ◽

Amorphous Solid Dispersion ◽

Solid State Characterization

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Characterization of Amorphous Solid Dispersion of Pharmaceutical Compound with pH-Dependent Solubility Prepared by Continuous-Spray Granulator

Pharmaceutics ◽

10.3390/pharmaceutics11040159 ◽

2019 ◽

Vol 11 (4) ◽

pp. 159 ◽

Cited By ~ 4

Author(s):

Ryoma Tanaka ◽

Yusuke Hattori ◽

Yukun Horie ◽

Hitoshi Kamada ◽

Takuya Nagato ◽

...

Keyword(s):

Solid Dispersion ◽

Process Development ◽

Amorphous Solid ◽

Amorphous Solid Dispersion ◽

Pharmaceutical Ingredients ◽

Solid Dosage ◽

Manufacturing Operations ◽

One Step ◽

Granulation Technology

A continuous-spray granulator (CTS-SGR) is a one-step granulation technology capable of using solutions or suspensions. The present research objectives were, (1) to reduce the manufacturing operations for solid dosage formulations, (2) to make amorphous solid dispersion (ASD) granules without pre-preparation of amorphous solids of active pharmaceutical ingredients (API), and (3) to characterize the obtained SGR granules by comprehensive pharmaceutical analysis. Rebamipide (RBM), a biopharmaceutical classification system class IV drug, that has low solubility or permeability in the stomach, was selected as a model compound. Five kind of granules with different concentrations of polyvinylpyrrolidone/vinyl acetate copolymer (PVP-VA) were prepared using a one-step SGR process. All of the SGR granules could be produced in amorphous or ASD form and their thermodynamic stability was very high because of high glass transition temperatures (>178 °C). They were unstable in 20 °C/75%RH; however, their stability was improved according to the proportion of polymer. The carboxy group of RBM was ionized in the granules and interactions appeared between RBM and PVP-VA, with the formation of an ASD confirmed and the solubility was enhanced compared with bulk RBM crystals. The SGR methodology has the possibility of contributing to process development in the pharmaceutical industry.

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