Amorphization within the tablet: Using microwave irradiation to form a glass solution in situ

Doreth, Maria; Hussein, Murtadha Abdul; Priemel, Petra A.; Grohganz, Holger; Holm, René; Diego, Heidi Lopez de; Rades, Thomas; Löbmann, Korbinian

doi:10.1016/j.ijpharm.2017.01.035

Cited by 40 publications

(55 citation statements)

References 31 publications

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“…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%

Section: Introductionmentioning

confidence: 99%

“…In situ drug amorphization is a novel approach to circumvent potential physical and chemical stability issues of amorphous solid dispersions (ASDs) during manufacturing and storage [1][2][3]. Using this approach, a crystalline drug is formulated together with a polymer into a final dosage form, for example, a compact, which subsequently can be "activated" into the amorphous form as a final manufacturing step or immediately prior to administration [2]. 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.…”

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: Resultsmentioning

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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“…Milling, for example, can induce a mechanically activated disordering of the crystalline API and thermal conductivity strongly influences the temperature increase needed for complete amorphisation [4]. Furthermore, developing novel formulation approaches such as in situ amorphisation-For example, the conversion of a drug to its amorphous form prior to administration to the patient with the help of microwave heating [5]-Would benefit from having established thermal conductivity values.…”

Section: Introductionmentioning

confidence: 99%

Determining Thermal Conductivity of Small Molecule Amorphous Drugs with Modulated Differential Scanning Calorimetry and Vacuum Molding Sample Preparation

Karl

Rantanen

2019

Pharmaceutics

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Thermal conductivity is a material specific property, which influences many aspects of pharmaceutical development, such as processing, modelling, analysis, and the development of novel formulation approaches. We have presented a method to measure thermal conductivity of small molecule organic glasses, based on a vacuum molding sample preparation technique combined with modulated differential scanning calorimetry. The method is applied to the two amorphous model compounds indomethacin and celecoxib. The measured values of below 0.2 W/m °C indicate very low thermal conductivity of the amorphous compounds, within the range of organic liquids and low conducting polymers.

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“…An interesting, and very recent, application of microwave irradiation is the concept of amorphisation within the tablet, i.e. creating the amorphous form of the drug in its final dosage form directly before administration [22].…”

Section: Introductionmentioning

confidence: 99%

Predicting the suitability of microwave formulation using microwave differential thermal analysis (MWDTA)

Waters

Ahmad

Parkes

2019

J Therm Anal Calorim

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Microwave-assisted formulation is becoming an established method of formulation in industry, providing a fast, economic and environmentally more favourable way to create products, such as those manufactured in the pharmaceutical industry. However, the effect of microwave-induced heating on a compound, or mixture of compounds, is yet to be fully explored, possibly indicating that this method of formulation may not be suitable in all cases. In this study, the effect of microwave heating was investigated through the application of microwave thermal analysis to six model pharmaceutical compounds and a set of four model excipients. Benzocaine, haloperidol, ibuprofen, indomethacin, ketoprofen and phenylbutazone were analysed, along with four excipients, namely b-cyclodextrin, D-mannitol, stearic acid and Syloid Ò XDP 3050 silica using microwave thermal analysis. Samples were heated by microwave irradiation at 5°C min-1 to a minimum of 160°C, held isothermally and then slowly cooled to room temperature. Thermal profiles were analysed and compared with data obtained using differential scanning calorimetry (DSC) and hot-stage microscopy (HSM). Overall, it was found that the process of microwave heating produced different thermal profiles to those seen using traditional, conductive heating. Investigating differences in thermal profiles can be a useful way to consider the effect of microwave-induced heating on formulations which can, in turn, help guide formulation choices.

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Amorphization within the tablet: Using microwave irradiation to form a glass solution in situ

Cited by 40 publications

References 31 publications

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

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

Determining Thermal Conductivity of Small Molecule Amorphous Drugs with Modulated Differential Scanning Calorimetry and Vacuum Molding Sample Preparation

Predicting the suitability of microwave formulation using microwave differential thermal analysis (MWDTA)

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