Selection of excipients for melt extrusion with two poorly water-soluble drugs by solubility parameter calculation and thermal analysis

Forster, Angus; Hempenstall, John; Tucker, Ian G.; Rades, Thomas

doi:10.1016/s0378-5173(01)00801-8

Cited by 349 publications

(202 citation statements)

References 15 publications

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“…To obtain a good compatibility between polymer and drug, the difference between solubility parameters (δ) of polymer and drug should be less than 2.0 MPa 1/2 [29] . When this is achieved, miscibility is optimal and, therefore, a glass solution can be formed during melt extrusion.…”

Section: Near-infrared Spectroscopymentioning

confidence: 99%

In-line NIR spectroscopy for the understanding of polymer–drug interaction during pharmaceutical hot-melt extrusion

Saerens

Dierickx

Quinten

et al. 2012

European Journal of Pharmaceutics and Biopharmaceutics

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The aim was to evaluate near-infrared spectroscopy for the in-line determination of the drug concentration, the polymer-drug solid-state behaviour and molecular interactions during hot-melt extrusion.Kollidon ® SR was extruded with varying metoprolol tartrate (MPT) concentrations (20, 30, and 40%) and monitored using NIR spectroscopy. A PLS model allowed drug concentration determination. The correlation between predicted and real MPT concentrations was good (R²=0.97). The predictive performance of the model was evaluated by the root mean square error of prediction, which was 1.54%. Kollidon®SR with 40% MPT was extruded at 105°C and 135°C to evaluate NIR spectroscopy for in-line polymer-drug solid state characterization.NIR spectra indicated the presence of amorphous MPT and hydrogen bonds between drug and polymer in the extrudates. More amorphous MPT and interactions could be found in the extrudates produced at 135°C than at 105°C. Raman spectroscopy, DSC and ATR FT-IR were used to confirm the NIR observations. Due to the instability of the formulation, only in-line Raman spectroscopy was an adequate confirmation tool. NIR spectroscopy is a potential PAT-tool for the in-line determination of API-concentration and for the polymer-drug solid state behaviour monitoring during pharmaceutical hot-melt extrusion.

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Section: Near-infrared Spectroscopymentioning

confidence: 99%

In-line NIR spectroscopy for the understanding of polymer–drug interaction during pharmaceutical hot-melt extrusion

Saerens

Dierickx

Quinten

et al. 2012

European Journal of Pharmaceutics and Biopharmaceutics

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“…A computational method in combination with a suitable force field provides an advantage in contrast to the commonly used group-number systems [9,43] for calculating the solubility [11]. Recent comparisons of simulated solubility parameters with solubility parameters measured using reverse gas chromatography and other experimental methods [44] proved the accurateness of the simulated values.…”

Section: I) Numerical Determination Of Solubility Propertiesmentioning

confidence: 99%

“…A common approach to cope with this problem is the calculation of the solubility parameters according to Hildebrand or Hansen [9][10][11][12], which is standard in the development of polymer mixtures [13]. The use of highly developed force fields as the basis of any MD simulation software enables the calculation of solubility parameters with an accuracy comparable to those measured experimentally by inverse gas chromatography [14] and an increasing number of other statistical quantitative property relationship (SQPR) between simulated and experimental values are established [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Molecular dynamics simulations for drug dosage form development: thermal and solubility characteristics for hot-melt extrusion

Maus

Wagner

Kornherr³

et al. 2008

Molecular Simulation

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“…31 The GordonTaylor equation is one of the most used expressions to describe the T g -composition dependence of miscible polymer blends 30,32 and drug/polymer blends 33,34 …”

Section: Resultsmentioning

confidence: 99%

Blends of Paclitaxel with POSS-Based Biodegradable Polyurethanes: Morphology, Miscibility, and Specific Interactions

Guo

Knight

Wu³

et al. 2010

Macromolecules

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The morphology, miscibility, and specific interactions of paclitaxel (PTx) with a family of polyhedral oligosilsesquioxane (POSS)-based biodegradable thermoplastic polyurethanes (POSS TPUs) were investigated systematically using wide-angle X-ray diffraction (WAXD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). These POSS TPUs incorporate an alternating multiblock structure formed by POSS hard segments and the soft segments composed of polylactide/caprolactone copolymer (P(DLLA-co-CL)). They feature variable poly(ethylene glycol) (PEG) content from 0 to 14 wt % through adjusting the poly(ethylene glycol) (PEG) molecular weight in P(DLLA-co-CL) soft segments of fixed molar mass of M _ n = 12 kg/mol and further to 52 wt % utilizing pure PEG M _ n = 1 kg/mol in the soft segments. Using WAXD, it was found that PTx is amorphous in all proportions in the PTx/POSS TPU blends prepared using a solutioncasting method. Interestingly, the PTx not only exhibits excellent miscibility in all of these PTx/POSS TPU blends over the whole range of the drug concentration, but also serves as an antiplasticizer by increasing the blend T g gradually from the polymer T g up to the T g of amorphous PTx. The T g -composition dependences in these blends were well fitted by the Gordon-Taylor equation. The glass transition breadth of the blends increases significantly only for drug concentrations higher than 50 wt % for most of the POSS TPUs, suggesting some spatial heterogeneity at these high drug concentrations. On the other hand, the slight increment of the blend melting temperature, T m , and latent heat, ΔH, indicates enhanced phase separation between the POSS hard segments and the TPU soft segments upon drug incorporation. Gordon-Taylor analysis and FTIR results confirm that the PEG incorporated in the POSS TPUs exhibits strong H-bonding interactions with the PTx. Although PEG can promote the favorable interactions in the PTx/POSS TPU blends, we showed that the more hydrophobic LA/CL repeat units are still required in the soft segments in order to achieve molecular-level miscibility. This systematic investigation of the PTx/POSS TPU systems may be of great value to design plasticizer/antiplasticizer for new polymer materials with controlled and tailored properties, especially for those PLA-or PCL-based biodegradable polymer systems.

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Selection of excipients for melt extrusion with two poorly water-soluble drugs by solubility parameter calculation and thermal analysis

Cited by 349 publications

References 15 publications

In-line NIR spectroscopy for the understanding of polymer–drug interaction during pharmaceutical hot-melt extrusion

In-line NIR spectroscopy for the understanding of polymer–drug interaction during pharmaceutical hot-melt extrusion

Molecular dynamics simulations for drug dosage form development: thermal and solubility characteristics for hot-melt extrusion

Blends of Paclitaxel with POSS-Based Biodegradable Polyurethanes: Morphology, Miscibility, and Specific Interactions

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