Oscillatory Shear Rheology in Examining the Drug-Polymer Interactions Relevant in Hot Melt Extrusion

Aho, Johanna; Edinger, Magnus; Boetker, Johan; Baldursdóttir, Stefanía; Rantanen, Jukka

doi:10.1016/j.xphs.2015.11.029

Cited by 38 publications

(34 citation statements)

References 39 publications

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“…The plasticizing effect can be observed by thermal analysis as a decrease in glass transition temperature (Tg), a change in melting temperature and crystalline pattern [26]. Some drugs possess the plasticizing ability by reducing the friction between the polymers and enables lowering the operating temperature, which can prevent them from thermal degradation (in the case of thermal sensitive drugs) [27,28].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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Effect of melt extrudability and melt binding efficiency of polyvinyl caprolactam polyvinyl acetate polyethylene glycol graft copolymer (Soluplus®) on release pattern of hydrophilic and high dose drugs

Ayyub

Moravkar

Maniruzzaman

et al. 2019

Materials Science and Engineering: C

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Section: Accepted Manuscriptmentioning

confidence: 99%

“…Where η represent viscosity coefficient, γ indicate shear rate and n is power law index. In case of shear thinning polymers, 0<n<1 [13,28].…”

Section: Rheological Evaluationmentioning

confidence: 99%

Effect of melt extrudability and melt binding efficiency of polyvinyl caprolactam polyvinyl acetate polyethylene glycol graft copolymer (Soluplus®) on release pattern of hydrophilic and high dose drugs

Ayyub

Moravkar

Maniruzzaman

et al. 2019

Materials Science and Engineering: C

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“…8,10,11,13,17 HME processes have been reported to produce two types of pharmaceutical formulations with respect to the solid state (amorphous or crystalline) of the API embedded in a polymeric carrier, known as a solid dispersion. 6,9,13 Recent studies demonstrated the feasibility of HME as an alternative continuous formulation strategy to produce crystalline solid dispersions, while improving the dissolution of APIs, an advantage often attributed to amorphous solid dispersions. 1,2,4,6,[19][20][21] Additionally, crystalline solid dispersions present a viable alternative to their amorphous counterparts due to their enhanced stability.…”

Section: Introductionmentioning

confidence: 99%

Revealing Polymorphic Phase Transformations in Polymer-Based Hot Melt Extrusion Processes

Espinell

López-Mejías

Stelzer

2018

Crystal Growth & Design

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The inadvertent occurrence of polymorphic phase transformations in active pharmaceutical ingredients (APIs) during hot melt extrusion (HME) processes has been claimed to limit the application of this technique. Hence, the control of polymorphism would need to be addressed if there is any prospect of HME to be successfully implemented as an alternative solid dosage formulation strategy in integrated, continuous end-to-end pharmaceutical manufacturing settings. This work demonstrates that flufenamic acid (FFA), one of the most polymorphic APIs known, thus far, can be processed using temperature-simulated HME with polyethylene glycol (PEG) as polymeric carrier. At temperatures above the transition point of FFA forms III and I (42 °C), the induction time of the polymorphic phase transformation is longer than the average reported residence time in conventional HME processes (5 min). Moreover, it was demonstrated that thorough understanding of the thermodynamic and kinetic design space for the PEG-FFA system leads to polymorphic control in the produced crystalline solid dispersions. Ultimately, this investigation helps to gain fundamental understanding of the processing needs of crystalline solid dispersions, which will lead to the broader application of HME as a continuous manufacturing strategy for drug products containing APIs prone to polymorphism, representing about 80% of all APIs.

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“…Temperature-based methods for the preparation of SDs present several advantages compared to alternatives, such as being environmentally friendly (solvent and dust free), process-efficient (continuous processing) etc. [25][26][27][28][29][30][31][32][33][34]. In such systems, thermoplastic matrix forming polymers are co-melted/cooled with API(s) in order to prepare several types of solid formulations, including eutectic mixtures, micro-or nano-sized crystalline (or semi-crystalline) solid dispersions or solid solutions (substitutional, interstitial or amorphous) [28,29,[35][36][37][38].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Dissolution Enhancement of Aprepitant Drug in Ternary Pharmaceutical Solid Dispersions with Soluplus® and Poloxamer 188 Prepared by Melt Mixing

Nanaki¹,

Eleftheriou²,

Barmpalexis³

et al. 2019

Sci

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In the present study Aprepitant (APT) ternary solid dispersions (SDs) were developed and evaluated for the first time. Specifically, ternary SDs of APT with Poloxamer 188 and Soluplus® (SOL) were prepared via melt mixing and compared to binary APT/Poloxamer 188 and APT/SOL SDs. Initially, combined thermo-gravimetric and hot-stage polarized light microscopy studies indicated that all tested compounds were thermally stable up to 280 °C, while Poloxamer 188 acted as a plasticizer to SOL by significantly reducing the temperature required to fully solubilize the API during SD preparation. Differential scanning calorimetry combined with wide angle X-ray diffraction studies showed that crystalline API was dispersed in both binary and ternary SDs, while Fourier transformation-infrared spectroscopy studies revealed no molecular interactions among the components. Scanning electron microscopy combined with EDAX element analysis showed that the API was dispersed in nano-scale within the polymer matrices, while increasing APT content led to increasing API nano-crystals within the SDs. Finally, dissolution studies showed that the prepared formulations enhanced dissolution of Aprepitant and its mechanism analysis was further studied. A mathematical model was also investigated to evaluate the drug release mechanism.

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Oscillatory Shear Rheology in Examining the Drug-Polymer Interactions Relevant in Hot Melt Extrusion

Cited by 38 publications

References 39 publications

Effect of melt extrudability and melt binding efficiency of polyvinyl caprolactam polyvinyl acetate polyethylene glycol graft copolymer (Soluplus®) on release pattern of hydrophilic and high dose drugs

Effect of melt extrudability and melt binding efficiency of polyvinyl caprolactam polyvinyl acetate polyethylene glycol graft copolymer (Soluplus®) on release pattern of hydrophilic and high dose drugs

Revealing Polymorphic Phase Transformations in Polymer-Based Hot Melt Extrusion Processes

Evaluation of Dissolution Enhancement of Aprepitant Drug in Ternary Pharmaceutical Solid Dispersions with Soluplus® and Poloxamer 188 Prepared by Melt Mixing

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