Soluplus&amp;reg;/TPGS-based solid dispersions prepared by hot-melt extrusion equipped with twin-screw systems for enhancing oral bioavailability of valsartan

Lee, Jae Eun; Kang, Wen; Piao, Jingpei; Yoon, In‐Soo; Kim, Dae‐Duk; Cho, Hyun‐Jong

doi:10.2147/dddt.s84070

Cited by 23 publications

(7 citation statements)

References 41 publications

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“…Still, Soluplus® has been shown to enhance solubility to a greater extent for certain APIs relative to other hydrophilic polymers (97). The utility of Soluplus® as a matrix polymer and solubility enhancer in melt-extruded ASDs has been demonstrated for multiple poorly water-soluble drugs, including carbamazepine (95,96,98), fenofibrate (99), simvastatin (100), dronedarone hydrochloride (101), and valsartan (102).…”

Section: Designer Polymers For Extrusion Processingmentioning

confidence: 99%

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

2015

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Abstract. Thermal processing of amorphous solid dispersions continues to gain interest in the pharmaceutical industry, as evident by several recently approved commercial products. Still, a number of pharmaceutical polymer carriers exhibit thermal or viscoelastic limitations in thermal processing, especially at smaller scales. Additionally, active pharmaceutical ingredients with high melting points and/or that are thermally labile present their own specific challenges. This review will outline a number of formulation and process-driven strategies to enable thermal processing of challenging compositions. These include the use of traditional plasticizers and surfactants, temporary plasticizers utilizing sub-or supercritical carbon dioxide, designer polymers tailored for hot-melt extrusion processing, and KinetiSol® Dispersing technology. Recent case studies of each strategy will be described along with potential benefits and limitations.

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Section: Designer Polymers For Extrusion Processingmentioning

confidence: 99%

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

2015

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“…32 The characteristic peaks 18.12 and 22.32°of TPGS were observed in the diffraction pattern of TPGS. 33 The XRD patterns of the polymeric-mixed micelles (F127 and TPGS) and micelles loaded with CyA displayed similar peak locations in XRD patterns, with no obvious peak broadening observed (Figure 6ib). However, the diffraction patterns present in the crystalline drug were absent in the micelles, indicating that the drug was molecularly dispersed in the freeze-dried material.…”

Section: Elementalmentioning

confidence: 80%

“…Reference spectra indicated that CyA existed in a crystalline state before incorporation into the micellar formulations (Figure ia); the diffractogram of raw CyA powder showed characteristic high-intensity diffraction peaks at 2θ values of 6.86° (011), 7.8° (102), 9.26° (110), 10.76° (112), 12.58° (022), 14.48° (201), 15.04° (202), 15.2° (210), 16.78° (124), 18.6° (131), 19.38° (132), 20.84° (027), 22.14° (230), 23.28° (042), and 24.28° (119). , Pure F127 also showed two characteristic peaks with the highest intensity at 2θ angles 19.13 and 23.32°, indicating that F127 is a crystalline adjuvant . The characteristic peaks 18.12 and 22.32° of TPGS were observed in the diffraction pattern of TPGS . The XRD patterns of the polymeric-mixed micelles (F127 and TPGS) and micelles loaded with CyA displayed similar peak locations in XRD patterns, with no obvious peak broadening observed (Figure ib).…”

Section: Resultsmentioning

confidence: 99%

Design and Characterization of Cyclosporine A-Loaded Nanofibers for Enhanced Drug Dissolution

Dubey¹,

Barker²,

Craig³

2020

ACS Omega

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Despite widespread use as an immunosuppressant, the therapeutic efficacy of the undecapeptide cyclosporine A (CyA) is compromised when given by the oral route because of the innate hydrophobicity of the drug molecule, potentially leading to poor aqueous solubility and bioavailability. The aim of this study was to develop and characterize nanofibers based on the water-miscible polymer polyvinylpyrrolidone (PVP), incorporating CyA preloaded into polymeric surfactants so as to promote micelle formation on hydration; therefore, this approach represents the novel combination of three dissolution enhancement methodologies, namely solid dispersion technology, micellar systems, and nanofibers with enhanced surface area. The preparation of the nanofibers was performed in two steps. First, mixed micelles composed of the water-soluble vitamin E derivative D-α-tocopheryl poly(ethylene glycol) 1000 succinate and the amphiphilic triblock polymer Pluronic F127 (Poloxamer 407) were prepared. The micelles were characterized in terms of size, surface charge, drug loading, and encapsulation efficiency using transmission electron microscopy, dynamic light scattering, Fourier-transform infrared spectroscopy, high-performance liquid chromatography, and scanning electron and atomic force microscopy analysis. Nanofibers composed of PVP and the drugloaded surfactant system were then prepared via electrospinning, with accompanying thermal, spectroscopic, and surface topological analysis. Dissolution studies indicated an extremely rapid dissolution profile for the fibers compared to the drug alone, while wettability studies also indicated a marked decrease in contact angle compared to the drug alone. Overall, the new approach appears to offer a viable means for considerably improving the dissolution of the hydrophobic peptide CyA, with associated implications for improved oral bioavailability.

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“…Across the studied range, there is an excellent agreement between the predicted and experimentally calculated SA and SP D values, as has been shown for other cocrystals. , The prediction is also independent of surfactant type, including both biorelevant and synthetic solubilizers. Formulations may require lower additive concentrations due to toxicity, such as for 1% TPGS. , In this case, multiple solubilizing additives may be selected so that the targeted SP D and SA values are reached at additive concentrations below GRAS values.…”

Section: Resultsmentioning

confidence: 99%

“…Formulations may require lower additive concentrations due to toxicity, such as for 1% TPGS. 50,51 In this case, multiple solubilizing additives may be selected so that the targeted SP D and SA values are reached at additive concentrations below GRAS values.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Cocrystal Solubility Advantage and Dose/Solubility Ratio Diagrams: A Mechanistic Approach To Selecting Additives and Controlling Dissolution–Supersaturation–Precipitation Behavior

2020

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Two of the main questions regarding cocrystal selection and formulation development are whether the will be stable and how fast can it dissolve the drug dose. Dissolving the drug dose may require cocrystals with a high solubility advantage over drug (SA = S CC /S D ), but these may have limited potential to sustain drug supersaturation. Thus, we propose a twofold approach to mitigate the risk of drug precipitation by optimizing thermodynamic (SA) and kinetic factors (nucleation inhibitors). This risk can be evaluated by considering the cocrystal SA and drug dose/solubility ratio (D 0D = C dose /S D ), which in tandem represent the maximum theoretical supersaturation that a cocrystal may generate, the driving force for drug precipitation, and the potential for dose-/solubility-limited absorption. cocrystals with SA and D 0D values above critical supersaturation are prone to rapid precipitation, often negating their utility as a solubility enhancement tool. This work presents a mechanistic approach to controlling the dissolution−supersaturation−precipitation behavior of cocrystal systems, whereby relationships between SA, D 0D , and the drugsolubilizing power of surfactants (SP D = S D,T /S D,aq ) are used to fine-tune cocrystal-inherent supersaturation by rational additive selection. Experimental results with danazol−vanillin cocrystal demonstrate how SA, D 0D , and SP D are key thermodynamic parameters to understanding the kinetic cocrystal behavior and how the risks of cocrystal development may be mitigated through the mechanistic formulation design.

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Soluplus®/TPGS-based solid dispersions prepared by hot-melt extrusion equipped with twin-screw systems for enhancing oral bioavailability of valsartan

Cited by 23 publications

References 41 publications

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

Design and Characterization of Cyclosporine A-Loaded Nanofibers for Enhanced Drug Dissolution

Cocrystal Solubility Advantage and Dose/Solubility Ratio Diagrams: A Mechanistic Approach To Selecting Additives and Controlling Dissolution–Supersaturation–Precipitation Behavior

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