The influence of drug and polymer particle size on the in situ amorphization using microwave irradiation

Hempel, Nele‐Johanna; Knopp, Matthias Manne; Berthelsen, Ragna; Zeitler, J. Axel; Löbmann, Korbinian

doi:10.1016/j.ejpb.2020.01.019

Cited by 25 publications

(73 citation statements)

References 38 publications

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“…Both sets of compacts showed small amounts of amorphous CCX prior to heating (0 min), i.e., 9.3% ± 1.6% (conditioned) and 8.4% ± 1.0% (dry) (n = 12). The small amount of initial amorphization may be due to the applied compaction pressure and/or occur during conditioning, as similar results have previously been reported [1,9,15]. In an attempt to calculate the necessary exposure time to obtain complete amorphization of the conditioned compacts through convection, a mathematical data fit was conducted using the data displayed in Figure 1a (0-20 min).…”

Section: Resultssupporting

confidence: 67%

“…Due to the high water content in the conditioned compacts, the compacts became soft. As sorbed water in the compacts has previously shown to act as a plasticizer through decreasing the T g of the polymer and increasing molecular mobility [2], the dissolution rate of the drug into the polymer during heating was proposed to increase with increasing water content [2,9]. Figure 1 shows the degree of amorphization achieved for the conditioned and dry compacts following convection heating for 0-30 min.…”

Section: Resultsmentioning

confidence: 99%

“…In situ amorphization of ASDs has been shown to be a promising concept, even though full amorphization was not achieved in several studies using either microwave radiation [2,[4][5][6] or by immersion in water [7,8], with the model drugs celecoxib (CCX), indomethacin, ibuprofen, and naproxen. Only recently, 100% amorphization was achieved using the microwave oven [9].…”

Section: Introductionmentioning

confidence: 99%

“…Here, only a small temperature gradient exists from the core of the material to the surface, due to a cooling effect of the surrounding air [10]. It has been suggested that the in situ amorphization process is driven by dissolution/fusion of the drug into the polymer at temperatures above the glass transition temperature (T g ) of the polymer [9,11,12]. Since internal heating within the compact during microwaving induces the in situ amorphization process, it is fundamentally interesting whether heating using a convection oven would yield similar results.…”

Section: Introductionmentioning

confidence: 99%

“…In this study, the suitability of the convection-induced in situ amorphization approach was investigated. To allow a direct comparison, the microwave oven setup described by Hempel et al (2020) was mimicked with respect to the maximum temperature reached during heating (100 • C) [9]. Furthermore, the influence of sorbed water was studied both as a source for heat conductivity and as a plasticizer.…”

Section: Introductionmentioning

confidence: 99%

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Convection-Induced vs. Microwave Radiation-Induced in situ Drug Amorphization

et al. 2020

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The aim of the study was to investigate the suitability of a convection oven to induce in situ amorphization. The study was conducted using microwave radiation-induced in situ amorphization as reference, as it has recently been shown to enable the preparation of a fully (100%) amorphous solid dispersion of celecoxib (CCX) in polyvinylpyrrolidone (PVP) after 10 min of continuous microwaving. For comparison, the experimental setup of the microwave-induced method was mimicked for the convection-induced method. Compacts containing crystalline CCX and PVP were prepared and either pre-conditioned at 75% relative humidity or kept dry to investigate the effect of sorbed water on the amorphization kinetics. Subsequently, the compacts were heated for 5, 10, 15, 20, or 30 min in the convection oven at 100 °C. The degree of amorphization of CCX in the compacts was subsequently quantified using transmission Raman spectroscopy. Using the convection oven, the maximum degree of amorphization achieved was 96.1% ± 2.1% (n = 3) for the conditioned compacts after 30 min of heating and 14.3% ± 1.4% (n = 3) for the dry compacts after 20 min of heating, respectively. Based on the results from the convection and the microwave oven, it was found that the sorbed water acts as a plasticizer in the conditioned compacts (i.e., increasing molecular mobility), which is advantageous for in situ amorphization in both methods. Since the underlying mechanism of heating between the convection oven and microwave oven differs, it was found that convection-induced in situ amorphization is inferior to microwave radiation-induced in situ amorphization in terms of amorphization kinetics with the present experimental setup.

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Section: Resultssupporting

confidence: 67%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Convection-Induced vs. Microwave Radiation-Induced in situ Drug Amorphization

et al. 2020

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Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies

Bhujbal

Mitra

Jain

et al. 2021

Acta Pharmaceutica Sinica B

280

131

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Amorphous solid dispersions (ASDs) are popular for enhancing the solubility and bioavailability of poorly water-soluble drugs. Various approaches have been employed to produce ASDs and novel techniques are emerging. This review provides an updated overview of manufacturing techniques for preparing ASDs. As physical stability is a critical quality attribute for ASD, the impact of formulation, equipment, and process variables, together with the downstream processing on physical stability of ASDs have been discussed. Selection strategies are proposed to identify suitable manufacturing methods, which may aid in the development of ASDs with satisfactory physical stability.

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