Dissolution of Indomethacin Crystals into a Polymer Melt: Role of Diffusion and Fragmentation

Moseson, Dana E.; Parker, Andrew S.; Gilpin, Christopher J.; Stewart, Andrew; Beaudoin, Stephen P.; Taylor, Lynne S.

doi:10.1021/acs.cgd.9b00200

Cited by 19 publications

(26 citation statements)

References 98 publications

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“…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%

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: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…It has been suggested previously, that the amorphization process of a drug in a polymer, at temperatures above the T g of the polymer, follows a dissolution process and is enhanced with increasing temperature above this temperature threshold. 22,56 Additionally, it was suggested that the temperature of the compact increases faster above, than below the T m of PEG due to the increased mobility of liquid PEG, as compared to solid PEG. In the present study, the temperature was measured on the surface of the compacts during exposure to microwave radiation in order to correlate it to the obtained rate and degree of amorphization.…”

Section: Analysis Of the Temperature Of The Compacts During In Situ Drug Amorphization And The Amorphization Kineticsmentioning

confidence: 99%

Microwave-Induced in Situ Drug Amorphization Using a Mixture of Polyethylene Glycol and Polyvinylpyrrolidone

Hempel

Knopp

Zeitler

et al. 2021

Journal of Pharmaceutical Sciences

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…On the other hand, physical mixture (Figure 9, band C) and solid co-evaporate (Figure 9, band D) of ETD with PEG 4000, showed complete disappearance of endothermic peak of the drug and the appearance of new endothermic peaks at both 58.9°C and 61.3°C for solid co-evaporate and physical mixture, respectively. The disappearance of ETD peak in case of physical mixture could be explained on the basis that the drug was dissolved in the molten polymer [46]. However, the complete disappearance of the endothermic peak of the ETD in its solid co-evaporate with PEG 4000 may be, also, attributed to the formation of the amorphous form of the drug [47].…”

Section: Differential Scanning Calorimetry (Dsc)mentioning

confidence: 99%

Utilization of Co-evaporation Technique for Enhancement the Solubility and Dissolution Rate of Etodolac

2021

J Pharmacol Pharm Res

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Etodolac (ETD), a member of non-steroidal anti-inflammatory drugs (NSAIDs), has a poor aqueous solubility. Long term administration of ETD causes severe gastrointestinal disturbances such as peptic ulcer and bleeding. The enhancement of its solubility and dissolution profile is expected to improve its bioavailability and reduce its side effects. In the present study, we tried to enhance the aqueous solubility and dissolution rate of ETD by two co-evaporation techniques. The first one is the formation of solid dispersion with different hydrophilic carriers, including polyethelene glycol (PEG 4000), polyvinyl pyrrolidones (PVP K25 and PVP K90) and urea. The second method is the formation of solid adsorbates using inert carriers such as avecil PH 101, bentonite and aerosil 200 as adsorbents. Co-evaporates were prepared at (1:1 w/w), (1:3 w/w) and (1:5 w/w) ETD to carrier ratios and the corresponding physical mixtures were also prepared. The solubility and dissolution studies of all formulations were measured. Moreover, the physicochemical properties of the modified co-evaporates were characterized using different techniques including, differential scanning calorimetry (DSC), infrared spectroscopy and X-ray diffractometry (XRD) analysis. The results showed that the co-evaporates exhibited higher dissolution rate than the corresponding physical mixtures and both showed higher dissolution rate than the unmodified drug. Increase polymer concentration led to increase in the dissolution rate of drug. Plus, the dissolution rate was enhanced by increasing the temperature of the dissolution medium. Avecil PH 101 exhibited the highest dissolution rate over all other polymers. Infrared studies showed no interaction between the drug and the investigated carrier. The DSC and XRD studies indicated the conversion of ETD to an amorphous state. The enhancement of the drug solubility may be attributed to the increase of drug surface area, the wettability, formation of hydrogen bonds and the conversion to amorphous state.

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Dissolution of Indomethacin Crystals into a Polymer Melt: Role of Diffusion and Fragmentation

Cited by 19 publications

References 98 publications

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

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

Microwave-Induced in Situ Drug Amorphization Using a Mixture of Polyethylene Glycol and Polyvinylpyrrolidone

Utilization of Co-evaporation Technique for Enhancement the Solubility and Dissolution Rate of Etodolac

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