Micro-scale prediction method for API-solubility in polymeric matrices and process model for forming amorphous solid dispersion by hot-melt extrusion

Bochmann, Esther S.; Neumann, Dirk; Gryczke, Andreas; Wagner, Karl G.

doi:10.1016/j.ejpb.2016.06.015

Cited by 43 publications

(18 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The complex viscosity graph shows that both PP and PS have a characteristic Newtonian plateau at low frequencies and a decrease at higher frequencies characteristic for a pseudoplastic behavior. The zero-shear viscosity was determined by fitting the experimental curves of shear rate sweep data through the modified Carreau-Yasuda model (see Supplementary Information Figure S1) for branched polymers [78,79] in Equation 5:…”

Section: Rheological Propertiesmentioning

confidence: 99%

Morphology, Rheology and Crystallization in Relation to the Viscosity Ratio of Polystyrene/Polypropylene Polymer Blends

et al. 2020

View full text Add to dashboard Cite

Microfibrillar and droplet morphology of polypropylene (PP) phase dispersed in polypropylene (PS) was fabricated by using melt-extrusion. This morphology was obtained by introducing isotactic PP (20 wt.%) with different viscosity in the PS matrix (80 wt.%). Furthermore, the rheological properties of the blend investigated as a function of the viscosity ratio K. The variations in blend morphology were related to crystallization, melting properties, and viscoelasticity. The blends with K >> 1 develop a fine morphology with PP microfibrils along the flow direction, while diameters of the dispersed PP droplets gradually increase with lower values of K = 1, or K << 1. Crystallinity of the prepared blends significantly decreases compared to neat PP, while the microfibrillar morphology induces homogeneous crystallization with small crystallites. This is reflected in a decrease of the crystallization temperature, small loss in the crystallinity, and lower melting temperature of the PS80/PP20 blend compared to neat PP. The storage moduli, loss moduli, and complex viscosity are highest for the microfibrillar morphology that presents retarded relaxation. The rheological properties are dominated by the dispersed phase (K > 1), or matrix (K < 1). The variation in blend properties with microfibrillar morphology can be clearly distinguished from heterogeneous blends containing PP droplets, providing an efficient tool to create a binary blend with unique properties.

show abstract

Section: Rheological Propertiesmentioning

confidence: 99%

Morphology, Rheology and Crystallization in Relation to the Viscosity Ratio of Polystyrene/Polypropylene Polymer Blends

et al. 2020

View full text Add to dashboard Cite

show abstract

“…While an amorphized drug tends towards recrystallization due to higher state of energy [7], ASDs may ensure physical stability by preserving the molecularly dispersed or amorphous state of the drug within a polymeric matrix [8]. Thereby, the drug can be in a thermodynamically stable state when its saturation solubility within the polymer is not exceeded at room temperature, or kinetically stabilized by means of reduced molecular mobility and increased glass transition temperature [9][10][11]. A further decisive feature of an ASD is the generation of a supersaturated solution, facilitated by an increased wettability and presence of the drug in the amorphous state [12].…”

Section: Introductionmentioning

confidence: 99%

Processing of Polyvinyl Acetate Phthalate in Hot-Melt Extrusion—Preparation of Amorphous Solid Dispersions

2020

Self Cite

View full text Add to dashboard Cite

The preparation of amorphous solid dispersions (ASDs) is a suitable approach to overcome solubility-limited absorption of poorly soluble drugs. In particular, pH-dependent soluble polymers have proven to be an excellently suitable carrier material for ASDs. Polyvinyl acetate phthalate (PVAP) is a polymer with a pH-dependent solubility, which is as yet not thoroughly characterized regarding its suitability for a hot-melt extrusion process. The objective of this study was to assess the processability of PVAP within a hot-melt extrusion process with the aim of preparing an ASD. Therefore, the influence of different process parameters (temperature, feed-rate) on the degree of degradation, solid-state and dissolution time of the neat polymer was studied. Subsequently, drug-containing ASDs with indomethacin (IND) and dipyridamole (DPD) were prepared, respectively, and analyzed regarding drug content, solid-state, non-sink dissolution performance and storage stability. PVAP was extrudable in combination with 10% (w/w) PEG 3000 as plasticizer. The dissolution time of PVAP was only slightly influenced by different process parameters. For IND no degradation occurred in combination with PVAP and single phased ASDs could be generated. The dissolution performance of the IND-PVAP ASD at pH 5.5 was superior and at pH 6.8 equivalent compared to commonly used polymers hydroxypropylmethylcellulose acetate succinate (HPMCAS) and Eudragit L100-55.

show abstract

“…Soluplus is a water-soluble copolymer with an average molecular weight ranging from 90,000 to 140,000 g/mol [7]. Soluplus has a hydrophobic core, which is able to entrap hydrophobic drug.…”

Section: Introductionmentioning

confidence: 99%

Development of functional docetaxel nanomicelles for treatment of brain glioma

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

View full text Add to dashboard Cite

The efficacy of anticancer drugs is rather limited in the treatment of brain glioma due to the hindrance of the blood-brain barrier (BBB). Herein, we reported an easy formulation of functional docetaxel nanomicelles for the treatment of brain glioma using a graft copolymer soluplus as basic material through dual-modifications with a glucose-lipid derivative and a dequalinium-lipid derivative. The studies were performed on brain glioma U87MG cells, in vitro BBB models and brain glioma-bearing nude mice. The functional docetaxel nanomicelles were approximately 100 nm. The results demonstrated that the functional docetaxel nanomicelles could transport across the BBB, enhance the cellular uptake, target to the mitochondria, induce the apoptosis, increase the cytotoxicity in the brain glioma cells, and extend survival span of the brain glioma-bearing mice. The action mechanisms were associated with dual-modifications by the glucose-lipid derivative and the dequalinium-lipid derivative, both of which are beneficial for the transport across the BBB. Furthermore, the modification with dequalinium-lipid derivative was able to target to the brain glioma cells and to the mitochondria. In conclusion, the functional docetaxel nanomicelles would be a promising formulation for the treatment of brain glioma, deserving further development for clinical trials.

show abstract

Micro-scale prediction method for API-solubility in polymeric matrices and process model for forming amorphous solid dispersion by hot-melt extrusion

Cited by 43 publications

References 40 publications

Morphology, Rheology and Crystallization in Relation to the Viscosity Ratio of Polystyrene/Polypropylene Polymer Blends

Morphology, Rheology and Crystallization in Relation to the Viscosity Ratio of Polystyrene/Polypropylene Polymer Blends

Processing of Polyvinyl Acetate Phthalate in Hot-Melt Extrusion—Preparation of Amorphous Solid Dispersions

Development of functional docetaxel nanomicelles for treatment of brain glioma

Contact Info

Product

Resources

About