Glass solution formation in water - In situ amorphization of naproxen and ibuprofen with Eudragit® E PO

Doreth, Maria; Löbmann, Korbinian; Holm, René; Diego, Heidi Lopez de; Priemel, Petra A.

doi:10.1016/j.jddst.2016.02.003

Cited by 31 publications

(22 citation statements)

References 30 publications

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“…These findings are in line with previous classifications reported in the literature [5,6]. It should be noted that even though it was not possible to fully amorphize GFA class 1 drugs on their own, several studies have shown that GFA class 1 drugs, such as naproxen, can form glass solutions using a polymer, another drug or an amino acid as co-former [26,27,28].…”

Section: Resultssupporting

confidence: 90%

The Influence of Polymers on the Supersaturation Potential of Poor and Good Glass Formers

et al. 2018

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The increasing number of poorly water-soluble drug candidates in pharmaceutical development is a major challenge. Enabling techniques such as amorphization of the crystalline drug can result in supersaturation with respect to the thermodynamically most stable form of the drug, thereby possibly increasing its bioavailability after oral administration. The ease with which such crystalline drugs can be amorphized is known as their glass forming ability (GFA) and is commonly described by the critical cooling rate. In this study, the supersaturation potential, i.e., the maximum apparent degree of supersaturation, of poor and good glass formers is investigated in the absence or presence of either hypromellose acetate succinate L-grade (HPMCAS-L) or vinylpyrrolidine-vinyl acetate copolymer (PVPVA64) in fasted state simulated intestinal fluid (FaSSIF). The GFA of cinnarizine, itraconazole, ketoconazole, naproxen, phenytoin, and probenecid was determined by melt quenching the crystalline drugs to determine their respective critical cooling rate. The inherent supersaturation potential of the drugs in FaSSIF was determined by a solvent shift method where the respective drugs were dissolved in dimethyl sulfoxide and then added to FaSSIF. This study showed that the poor glass formers naproxen, phenytoin, and probenecid could not supersaturate on their own, however for some drug:polymer combinations of naproxen and phenytoin, supersaturation of the drug was enabled by the polymer. In contrast, all of the good glass formers—cinnarizine, itraconazole, and ketoconazole—could supersaturate on their own. Furthermore, the maximum achievable concentration of the good glass formers was unaffected by the presence of a polymer.

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Section: Resultssupporting

confidence: 90%

The Influence of Polymers on the Supersaturation Potential of Poor and Good Glass Formers

et al. 2018

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“…[18] Like Eudragit E, 1 contains a tertiary amine side chain making it possess low aqueous solubility as the free base but become soluble once ionised. [19] The successful preparation of 1 was confirmed by 1 H NMR spectroscopy with the stacked spectra of each monomer and 1 shown in Fig 5.…”

Section: Coating Of Cao 2 Nps With Polymer 1 To Form 1-cao 2 Npsmentioning

confidence: 83%

Oxygen generating nanoparticles for improved photodynamic therapy of hypoxic tumours

Sheng

Nesbitt

Callan

et al. 2017

Journal of Controlled Release

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Photodynamic therapy (PDT) is a clinically approved anti-cancer treatment that involves the activation of an otherwise inactive sensitiser drug with light, which in the presence of molecular oxygen, generates cytotoxic reactive oxygen species (ROS). As oxygen is a key requirement for the generation of ROS in PDT and given the fact that hypoxia is a characteristic of most solid cancerous tumours, treating hypoxic tumours using PDT can be a challenge. In this manuscript, we have prepared a CaO nanoparticle (NP) formulation coated with a pH-sensitive polymer to enable the controlled generation of molecular oxygen as a function of pH. The polymer coat was designed to protect the particles from decomposition while in circulation but enable their activation at lower pH values in hypoxic regions of solid tumours. The oxygen generating capability of the polymer coated NPs was demonstrated in aqueous solution with minimal oxygen produced at pH7.4, whereas it increased significantly when the pH was reduced to 6.2. The polymer coated CaO NPs were also observed to significantly increase tumour pO levels (p<0.05) in mice bearing ectopic human xenograft MIA PaCa-2 pancreatic tumours with an average increase in tumour pO of 6.5mmHg in the period 10-30min following administration. A statistically significant improvement in PDT mediated efficacy (p<0.001) was also observed when the particles were administered to mice bearing the same tumours 20min prior to PDT treatment. These results suggest that the polymer coated CaO NP formulation offers significant potential as an in situ method for oxygen generation to enhance the efficacy of treatments that depend on the presence of oxygen to elicit a cytotoxic effect.

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“…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. Only recently, 100% amorphization was achieved using the microwave oven [9].…”

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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Glass solution formation in water - In situ amorphization of naproxen and ibuprofen with Eudragit® E PO

Cited by 31 publications

References 30 publications

The Influence of Polymers on the Supersaturation Potential of Poor and Good Glass Formers

The Influence of Polymers on the Supersaturation Potential of Poor and Good Glass Formers

Oxygen generating nanoparticles for improved photodynamic therapy of hypoxic tumours

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

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