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Hot-Melt Extrusion: a Roadmap for Product Development

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Abstract

Hot-melt extrusion has found extensive application as a feasible pharmaceutical technological option over recent years. HME applications include solubility enhancement, taste masking, and sustained drug release. As bioavailability enhancement is a hot topic of today’s science, one of the main applications of HME is centered on amorphous solid dispersions. This review describes the most significant aspects of HME technology and its use to prepare solid dispersions as a drug formulation strategy to enhance the solubility of poorly soluble drugs. It also addresses molecular and thermodynamic features critical for the physicochemical properties of these systems, mainly in what concerns miscibility and physical stability. Moreover, the importance of applying the Quality by Design philosophy in drug development is also discussed, as well as process analytical technologies in pharmaceutical HME monitoring, under the current standards of product development and regulatory guidance.

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Abbreviations

AG:

Adam–Gibbs

ASD:

Amorphous solid dispersions

BA:

Bioavailability

BCS:

Biopharmaceutical Classification Systems

CPP:

Critical process parameter

CQA:

Critical Quality Attribute

DoE:

Design of Experiments

DSC:

Differential Calorimetric Screening

FDA:

Food and Drug Administration USA

Tg :

Glass transition temperature

HME:

Hot-melt extrusion

HPC:

Hydroxypropyl cellulose

HPMC:

Hydroxypropyl methylcellulose (hypromellose)

HPMCAS:

Hypromellose acetate succinate

ICH:

International Conference on Harmonization

KWW:

Kohlrausch–Williams–Watts

MPD:

Melting point depression

Tm :

Melting temperature (Tm)

PATs:

Process Analytical Technologies

PEG:

Polyethylene glycol

PVP:

Poly(vinylpyrrolidone)

QbD:

Quality by Design

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Acknowledgements

The authors thank Teresa Filipe for her support on illustrations.

Funding

This work was supported by Bluepharma, Coimbra, Portugal, and by Fundação para a Ciência e Tecnologia (FCT), Portugal (Ph.D. fellowship PD/BDE/135149/2017).

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Authors and Affiliations

  1. Bluepharma - Indústria Farmacêutica, São Martinho do Bispo, 3045-016, Coimbra, Portugal

    Marta F. Simões, Rui M. A. Pinto & Sérgio Simões

  2. Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal

    Marta F. Simões & Sérgio Simões

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  1. Marta F. Simões
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  2. Rui M. A. Pinto
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  3. Sérgio Simões
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Correspondence to Sérgio Simões.

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Simões, M.F., Pinto, R.M.A. & Simões, S. Hot-Melt Extrusion: a Roadmap for Product Development. AAPS PharmSciTech 22, 184 (2021). https://doi.org/10.1208/s12249-021-02017-7

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