Is a distinctive single Tg a reliable indicator for the homogeneity of amorphous solid dispersion?

Qian, Feng; Huang, Jun; Zhu, Qi; Haddadin, Raja; Gawel, John; Garmise, Robert J.; Hussain, Munir

doi:10.1016/j.ijpharm.2010.05.033

Cited by 135 publications

(111 citation statements)

References 16 publications

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“…In particular, it is of interest to know whether the absorption of moisture by the system will result in the formation of amorphous API-rich and polymer-rich regions. This behavior is important to anticipate because the formation of an amorphous phase with API-rich and polymer-rich regions has been linked to accelerated API crystallization rates in a number of systems (3,15,16). In addition, any changes in the miscibility of an ASD can also potentially influence the dissolution behavior of the API.…”

Section: Discussionmentioning

confidence: 99%

Understanding the Tendency of Amorphous Solid Dispersions to Undergo Amorphous–Amorphous Phase Separation in the Presence of Absorbed Moisture

et al. 2011

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Abstract. Formulation of an amorphous solid dispersion (ASD) is one of the methods commonly considered to increase the bioavailability of a poorly water-soluble small-molecule active pharmaceutical ingredient (API). However, many factors have to be considered in designing an API-polymer system, including any potential changes to the physical stability of the API. In this study, the tendency of ASD systems containing a poorly water-soluble API and a polymer to undergo amorphous-amorphous phase separation was evaluated following exposure to moisture at increasing relative humidity. Infrared spectroscopy was used as the primary method to investigate the phase behavior of the systems. In general, it was observed that stronger drug-polymer interactions, low-ASD hygroscopicity, and a less hydrophobic API led to the formation of systems resistant to moisture-induced amorphous-amorphous phase separation. Orthogonal partial least squares analysis provided further insight into the systems, confirming the importance of the aforementioned properties. In order to design a more physically stable ASD that is resistant to moisture-induced amorphous-amorphous phase separation, it is important to consider the interplay between these properties.

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Section: Discussionmentioning

confidence: 99%

Understanding the Tendency of Amorphous Solid Dispersions to Undergo Amorphous–Amorphous Phase Separation in the Presence of Absorbed Moisture

et al. 2011

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“…5 The T g , however, has been shown to be a poor indicator of phase separation in many cases. [21][22][23][24] Thus, despite that the potential electrospinning has shown for producing amorphous formulations, it is still necessary to find conclusive evidence that the end result is a solid solution prior to utilizing this technology to create final solid dosage forms.…”

Section: Introductionmentioning

confidence: 99%

Solid-State NMR Characterization of High-Loading Solid Solutions of API and Excipients Formed by Electrospinning

Brettmann

Bell

Myerson

et al. 2012

Journal of Pharmaceutical Sciences

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“…A result of the thermal analysis shown in Table I suggested all three ASD materials have single and similar T g (glass transition temperature) and some minor differences in heat capacity (C p ). All the results above suggested that the materials generated by three different process were comparable macroscopically (30,31).…”

Section: Thermal Pxrd and Dsc Analysismentioning

confidence: 71%

In Vitro and In Vivo Evaluation of Amorphous Solid Dispersions Generated by Different Bench-Scale Processes, Using Griseofulvin as a Model Compound

Chiang¹,

Cui²,

Ran³

et al. 2013

AAPS J

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Abstract. Drug polymer-based amorphous solid dispersions (ASD) are widely used in the pharmaceutical industry to improve bioavailability for poorly water-soluble compounds. Spray-drying is the most common process involved in the manufacturing of ASD material. However, spray-drying involves a high investment of material quantity and time. Lower investment manufacturing processes such as fast evaporation and freeze-drying (lyophilization) have been developed to manufacture ASD at the bench level. The general belief is that the overall performance of ASD material is thermodynamically driven and should be independent of the manufacturing process. However, no formal comparison has been made to assess the in vivo performance of material generated by different processes. This study compares the in vitro and in vivo properties of ASD material generated by fast evaporation, lyophilization, and spray-drying methods using griseofulvin as a model compound and hydroxypropyl methylcellulose acetate succinate as the polymer matrix. Our data suggest that despite minor differences in the formulation release properties and stability of the ASD materials, the overall exposure is comparable between the three manufacturing processes under the conditions examined. These results suggest that fast evaporation and lyophilization may be suitable to generate ASD material for oral evaluation. However, caution should be exercised since the general applicability of the present findings will need to be further evaluated.

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Is a distinctive single Tg a reliable indicator for the homogeneity of amorphous solid dispersion?

Cited by 135 publications

References 16 publications

Understanding the Tendency of Amorphous Solid Dispersions to Undergo Amorphous–Amorphous Phase Separation in the Presence of Absorbed Moisture

Understanding the Tendency of Amorphous Solid Dispersions to Undergo Amorphous–Amorphous Phase Separation in the Presence of Absorbed Moisture

Solid-State NMR Characterization of High-Loading Solid Solutions of API and Excipients Formed by Electrospinning

In Vitro and In Vivo Evaluation of Amorphous Solid Dispersions Generated by Different Bench-Scale Processes, Using Griseofulvin as a Model Compound

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