The effect of processing on the surface physical stability of amorphous solid dispersions

Yang, Ziyi; Nollenberger, Kathrin; Albers, Jessica; Moffat, Jonathan; Craig, Duncan Q.M.; Qi, Sheng

doi:10.1016/j.ejpb.2014.07.013

Cited by 22 publications

(12 citation statements)

References 40 publications

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“…More sensitive methods to detect the beginning of drug recrystallisation and to monitor the growth of drug crystals in their ASDs are thus highly desired [265]. A series of new protocols has been investigated to this end [266][267][268][269][270]. The Nagy group recently investigated the applications of some of these methods to monitor drug recrystallisation in electrospun ASDs and to determine their long-term stability.…”

Section: Stabilitymentioning

confidence: 99%

Electrospun amorphous solid dispersions of poorly water-soluble drugs: A review

Williams

et al. 2018

Journal of Controlled Release

244

156

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The development of oral dosage forms for poorly water-soluble active pharmaceutical ingredients (APIs) is a persistent challenge. A range of methods has been explored to address this issue, and amorphous solid dispersions (ASDs) have received increasing attention. ASDs are typically prepared by starting with a liquid precursor (a solution or melt) and applying energy for solidification. Many techniques can be used, with the emergence of electrospinning as a potent option in recent years. This method uses electrical energy to induce changes from liquid to solid. Through the direct applications of electrical energy, electrospinning can generate nanofiber-based ASDs from drug-loaded solutions, melts and melt-solutions. The technique can also be combined with other approaches using the application of mechanical, thermal or other energy sources. Electrospinning has numerous advantages over other approaches to produce ASDs. These advantages include extremely rapid drying speeds, ease of implentation, compatibility with a wide range of active ingredients (including those which are thermally labile), and the generation of products with large surface areas and high porosity. Furthermore, this technique exhibits the potential to create so-called 'fifth-generation' ASDs with nanostructured architectures, such as core/shell or Janus systems and their combinations. These advanced systems can improve dissolution behaviour and provide programmable drug release profiles. Additionally, the fiber components and their spatial distributions can be precisely controlled. Electrospun fiber-based ASDs can maintain an incorporated active ingredient in the amorphous physical form for prolonged periods of time because of their homogeneous drug distribution within the polymer matrix (typically they comprise solid solutions), and ability to inhibit molecular motion. These ASDs can be utilised to generate oral dosage forms for poorly water-soluble drugs, resulting in linear or multiple-phase release of one or more APIs. Electrospun ASDs can also be exploited as templates for manipulating molecular self-assembly, offering a bridge between ASDs and other types of dosage forms. This review addresses the development, advantages and pharmaceutical applications of electrospinning for producing polymeric ASDs. Material preparation and analysis procedures are considered. The mechanisms through which performance has been improved are also discussed.

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Section: Stabilitymentioning

confidence: 99%

Electrospun amorphous solid dispersions of poorly water-soluble drugs: A review

Williams

et al. 2018

Journal of Controlled Release

244

156

View full text Add to dashboard Cite

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“…The most commonly used analytical techniques to quantify crystalline content within APIs and API formulations include the use of differential scanning calorimetry (DSC), , powder X-ray diffractometry (PXRD), − spectrochemical techniques including Raman, − and solid state nuclear magnetic resonance (ssNMR) . Unfortunately, these methods have detection limits around 1–2% crystallinity under routine conditions, which can be particularly problematic when drug loadings are low within a formulation.…”

mentioning

confidence: 99%

Triboluminescence from Pharmaceutical Formulations

et al. 2018

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Triboluminescence (TL) is shown to enable selective detection of trace crystallinity within nominally amorphous solid dispersions (ASDs). ASDs are increasingly used for the preparation of pharmaceutical formulations, the physical stability of which can be negatively impacted by trace crystallinity introduced during manufacturing or storage. In the present study, TL measurements of a model ASD consisting of griseofulvin in polyethylene glycol produced limits of detection of 140 ppm. Separate studies of the particle size dependence of sucrose crystals and the dependence on polymorphism in clopidogrel bisulfate particles are both consistent with a mechanism for TL closely linked to the piezoelectric response of the crystalline fraction. Whereas disordered polymeric materials cannot support piezoelectric activity, molecular crystals produced from homochiral molecules adopt crystal structures that are overwhelmingly symmetry-allowed for piezoelectricity. Consequently, TL may provide a broadly applicable and simple experimental route for sensitive detection of trace crystallinity within nominally amorphous materials.

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“…In order to predict and assess the physical stability of the ASD formulation, the continuous monitoring of crystallization of drug from the amorphous system can be utilized. Many efforts were made to develop the crystallization kinetics of the amorphous drug in a different polymeric matrix [23,24,25,26]. The correlations between key physicochemical parameters of the polymers may be obtained and offer potential useful guidance for the selection of right carriers.…”

Section: Introductionmentioning

confidence: 99%

The Investigation of Flory–Huggins Interaction Parameters for Amorphous Solid Dispersion Across the Entire Temperature and Composition Range

et al. 2019

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Amorphous solid dispersion (ASD) is one of the most promising enabling formulations featuring significant water solubility and bioavailability enhancements for biopharmaceutical classification system (BCS) class II and IV drugs. An accurate thermodynamic understanding of the ASD should be established for the ease of development of stable formulation with desired product performances. In this study, we report a first experimental approach combined with classic Flory–Huggins (F–H) modelling to understand the performances of ASD across the entire temperature and drug composition range. At low temperature and drug loading, water (moisture) was induced into the system to increase the mobility and accelerate the amorphous drug-amorphous polymer phase separation (AAPS). The binodal line indicating the boundary between one phase and AAPS of felodipine, PVPK15 and water ternary system was successfully measured, and the corresponding F–H interaction parameters (χ) for FD-PVPK15 binary system were derived. By combining dissolution/melting depression with AAPS approach, the relationship between temperature and drug loading with χ (Φ, T) for FD-PVPK15 system was modelled across the entire range as χ = 1.72 − 852/T + 5.17·Φ − 7.85·Φ2. This empirical equation can provide better understanding and prediction for the miscibility and stability of drug-polymer ASD at all conditions.

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The effect of processing on the surface physical stability of amorphous solid dispersions

Cited by 22 publications

References 40 publications

Electrospun amorphous solid dispersions of poorly water-soluble drugs: A review

Electrospun amorphous solid dispersions of poorly water-soluble drugs: A review

Triboluminescence from Pharmaceutical Formulations

The Investigation of Flory–Huggins Interaction Parameters for Amorphous Solid Dispersion Across the Entire Temperature and Composition Range

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