Stability-enhanced Hot-melt Extruded Amorphous Solid Dispersions via Combinations of Soluplus® and HPMCAS-HF

Alshahrani, Saad; Lu, Wenli; Park, Jun-Bom; Morott, Joseph T.; Alsulays, Bader B.; Majumdar, Soumyajit; Langley, Nigel; Kolter, Karl; Gryczke, Andreas; Repka, Michael A.

doi:10.1208/s12249-014-0269-6

Cited by 84 publications

(38 citation statements)

References 24 publications

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“…Alshahrani et al (69) utilized HME technology in the preparation of carbamazepine (CBZ) solid dispersions using a novel combination of Soluplus® and the HF grade of the polymer hydroxypropyl methylcellulose acetate succinate (HPMCAS-HF, also called hypromellose acetate succinate in pharmaceutical applications) to enhance the solubility and physicochemical stability of the amorphous solid dispersion product. Soluplus® is polyethylene-glycol-polyvinyl caprolactam-polyvinyl acetate-grafted copolymer that was specifically designed and developed for HME by BASF SE.…”

Section: Pharmaceutical Applications Of Hme Solid Dispersions For Solmentioning

confidence: 99%

“…The FTIR data demonstrated that the intensity of the hydrogen bonding was increased by the addition of HPMCAS-HF, which worked synergistically with the Soluplus® to enhance the solubility and stability of the formulation. These researchers also studied the effect of the polymer ratio on the extrudability and dissolution profile and found that the release of CBZ was enhanced with an increase in the percentage of Soluplus® (69).…”

Section: Pharmaceutical Applications Of Hme Solid Dispersions For Solmentioning

confidence: 99%

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Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

2015

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Abstract. Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. In drug discovery and development, industry estimates that more than 50% of active pharmaceutical ingredients currently used belong to the biopharmaceutical classification system II (BCS class II), which are characterized as poorly water-soluble compounds and result in formulations with low bioavailability. Therefore, there is a critical need for the pharmaceutical industry to develop formulations that will enhance the solubility and ultimately the bioavailability of these compounds. HME technology also offers an opportunity to earn intellectual property, which is evident from an increasing number of patents and publications that have included it as a novel pharmaceutical formulation technology over the past decades. This review had a threefold objective. First, it sought to provide an overview of HME principles and present detailed engineered extrusion equipment designs. Second, it included a number of published reports on the application of HME techniques that covered the fields of solid dispersions, microencapsulation, taste masking, targeted drug delivery systems, sustained release, films, nanotechnology, floating drug delivery systems, implants, and continuous manufacturing using the wet granulation process. Lastly, this review discussed the importance of using the quality by design approach in drug development, evaluated the process analytical technology used in pharmaceutical HME monitoring and control, discussed techniques used in HME, and emphasized the potential for monitoring and controlling hot-melt technology.

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Section: Pharmaceutical Applications Of Hme Solid Dispersions For Solmentioning

confidence: 99%

Section: Pharmaceutical Applications Of Hme Solid Dispersions For Solmentioning

confidence: 99%

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

2015

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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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“…14) Considering this background, Soluplus ® has been applied to solid dispersion formulations prepared by freeze-drying, spraydrying, and melt-extrusion techniques to enhance the solubility and bioavailability of poorly water-soluble compounds. [15][16][17] However, the solubilizing mechanism of Soluplus ® ascribed to micellization has yet to be elucidated. The self-organization of surfactants and amphiphilic polymers into micelles has been widely researched using many analytical methods, including the measurement of surface tension, Fourier transform infrared spectroscopy, relaxation studies using 1 H nuclear magnetic resonance, fluorescence spectroscopy, and isothermal titration calorimetry (ITC).…”

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confidence: 99%

Evaluation of the Micellization Mechanism of an Amphipathic Graft Copolymer with Enhanced Solubility of Ipriflavone

et al. 2016

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The main purpose of this study was to investigate the solubilization enhancement properties of an amphipathic graft copolymer, Soluplus ® , on test compounds. Micellization of Soluplus ® in solution was characterized by evaluating the changes in the surface activity, turbidity, and thermodynamic behavior. To assess the feasibility of Soluplus ® as a polymeric carrier of solid dispersions, freeze-dried samples of ipriflavone were prepared, and the physicochemical properties of the carrier plus ipriflavone were evaluated in terms of solubility, dissolution, and crystallinity. The surface tension of the solution decreased depending on the polymer concentration, and gradual turbidity increase was observed. Isothermal titration calorimetry was used to measure the thermal reaction accompanying the micellization of Soluplus ® and indicated that a colloidal micelle formation improved solubility. The prepared formulations, particularly at a ratio of ipriflavone : Soluplus ® 1 : 10 (w/w) exhibited a dramatically improved solubility of ipriflavone that was ca. 70-fold higher than that of untreated ipriflavone. The solubilization mechanism of Soluplus ® was partially elucidated and suggested that its strategic application could improve the solubility of hydrophobic compounds.Key words isothermal titration calorimetry; ipriflavone; amphipathic graft copolymer; solubility Among the available technologies, the solid dispersion technique is commonly used as one of the most promising strategies for the enhancement of the solubility, dissolution rate, and bioavailability of poorly water-soluble compounds. A solid dispersion system can be defined as a distribution of active pharmaceutical ingredients as molecular amorphous particles and/or in the microcrystalline state into a carrier matrix-like polymer.1) The physicochemical characteristics of polymeric carriers could dominate the pharmaceutical properties of a solid dispersion system. 2,3) Based on the characteristic properties of a polymeric carrier, a number of solid dispersion systems possessing various functional properties such as sustained release, pH-dependent release, self-emulsifying properties, and site-specific release have been developed. [4][5][6][7] In particular, amphiphilic polymers have been found to be beneficial for the enhancement of not only solubility but also of the oral bioavailability of poorly water-soluble compounds because they form micellar structures that contain the compound. 6,8) Soluplus ® , a graft copolymer consisting of polyvinyl caprolactam, polyvinyl acetate, and polyethyleneglycol, has been applied to the design of solid-dispersion formulations with poorly water-soluble substances to improve their solubility and bioavailability.9,10) The copolymer exhibits an amphipathic property attributed to its hydrophilic and hydrophobic residues, which could contribute to the formation of micelles in water. Unlike conventional polymers such as polyvinylpyrrolidone and hydroxypropyl methylcellulose, Soluplus ® is bifunctional and can act as both a polym...

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Stability-enhanced Hot-melt Extruded Amorphous Solid Dispersions via Combinations of Soluplus® and HPMCAS-HF

Cited by 84 publications

References 24 publications

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

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

Evaluation of the Micellization Mechanism of an Amphipathic Graft Copolymer with Enhanced Solubility of Ipriflavone

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