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Review
. 2020 Jul 11;12(7):655.
doi: 10.3390/pharmaceutics12070655.

Microwave-Induced In Situ Amorphization: A New Strategy for Tackling the Stability Issue of Amorphous Solid Dispersions

Wei Qiang  1 , Korbinian Löbmann  2 , Colin P McCoy  1 , Gavin P Andrews  1   3 , Min Zhao  1   3
Affiliations
Review

Microwave-Induced In Situ Amorphization: A New Strategy for Tackling the Stability Issue of Amorphous Solid Dispersions

Wei Qiang et al. Pharmaceutics. .

Abstract

The thermodynamically unstable nature of amorphous drugs has led to a persistent stability issue of amorphous solid dispersions (ASDs). Lately, microwave-induced in situ amorphization has been proposed as a promising solution to this problem, where the originally loaded crystalline drug is in situ amorphized within the final dosage form using a household microwave oven prior to oral administration. In addition to circumventing issues with physical stability, it can also simplify the problematic downstream processing of ASDs. In this review paper, we address the significance of exploring and developing this novel technology with an emphasis on systemically reviewing the currently available literature in this pharmaceutical arena and highlighting the underlying mechanisms involved in inducing in situ amorphization. Specifically, in order to achieve a high drug amorphicity, formulations should be composed of drugs with high solubility in polymers, as well as polymers with high hygroscopicity and good post-plasticized flexibility of chains. Furthermore, high microwave energy input is considered to be a desirable factor. Lastly, this review discusses challenges in the development of this technology including chemical stability, selection criteria for excipients and the dissolution performance of the microwave-induced ASDs.

Keywords: amorphous solid dispersions; in situ amorphization; microwave irradiation; physical stability; poorly soluble drugs.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Crystallinity of IND (%, w/w) versus energy input during microwaving of compacts that had been stored at 32%, 43% or 54% RH and microwaved at nine different settings. (Reproduced from [22]).
Figure 2
Figure 2
Scanning electron micrographs of the cross section of IND:PVP K12, IND:PVP K17 and IND:PVP K25 compacts after storage under dry conditions, 54% RH and after subsequent processing with 90 kJ and 180 kJ microwave energy. (Reproduced from [46]). The highest extent of pore network reduction is highlighted by the red square.
Figure 3
Figure 3
Degree of amorphization for the drug CCX plotted against the compact temperature obtained during microwaving at different exposure times. Two compacts containing CCX and the polymer PVP K12 with different particle sizes are shown, where c/p and C/P refer to small and large sizes of CCX/PVP, respectively. Mean ± SD (n = 3). The dashed lines indicate different Tgs. (Reproduced from [86]).
Figure 4
Figure 4
Dissolution profiles of IND:PVP K12, IND:PVP K17 and IND:PVP K25 compacts after microwaving with an energy input of 180 kJ. (Reproduced from [46]).
See this image and copyright information in PMC

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