Relapsing-remitting multiple sclerosis is a chronic inflammatory disease of the central nervous s... more Relapsing-remitting multiple sclerosis is a chronic inflammatory disease of the central nervous system. Solid dosage forms in capsules of dimethyl fumarate (DMF) are currently used as first line treatment [1], [2]. However, the gastrointestinal side effects, the limited solubility and the low stability, limit its therapeutic efficacy. To overcome this issues, binary systems of DMF and semisynthetic derivatives of β-cyclodextrin (β-CD), in particular hydroxypropyl (HPβCD) and randomly methylated β-CD (RAMEB) were prepared with the aim to improve its bioavailability and allow its administration by the nasal route [3]. Complexes by kneading method, at 1:1 and 1:2 molar ratios, were prepared and characterized by means of differential scanning calorimetry (DSC) supported by FT-IR analyses in order to point out the solid-state interaction between the two components. Phase solubility studies were performed according to Higuchi and Connors method, with a concentration of CD ranging from 0 to 200 mM. Stability studies have been performed in order to verify how much the presence of CD can influence the degradation process of the drug; the results within 14 days showed that the binary systems slowed down the DMF degradation process. Solutions of DMF and the kneading products were freeze-dried, according to a design of experiment plan, to evaluate the effect of complexation on relevant stability aspects and quantify the presence of degradation products monomethyl fumarate and fumaric acid. RAMEB:DMF at 2:1 molar ratio seemed the most suitable system for DMF stabilization. The present work highlights how CDs can be a valid tool to increase the water solubility and stability of the drug, with interesting perspectives in relation to a possible nasal application.
V. Symposium of Young Researchers on Pharmaceutical Technology, Biotechnology and Regulatory Science, 2023
Relapsing-remitting multiple sclerosis is a chronic inflammatory disease of the central nervous s... more Relapsing-remitting multiple sclerosis is a chronic inflammatory disease of the central nervous system. Solid dosage forms in capsules of dimethyl fumarate (DMF) are currently used as first line treatment [1], [2]. However, the gastrointestinal side effects, the limited solubility and the low stability, limit its therapeutic efficacy. To overcome this issues, binary systems of DMF and semisynthetic derivatives of β-cyclodextrin (β-CD), in particular hydroxypropyl (HPβCD) and randomly methylated β-CD (RAMEB) were prepared with the aim to improve its bioavailability and allow its administration by the nasal route [3]. Complexes by kneading method, at 1:1 and 1:2 molar ratios, were prepared and characterized by means of differential scanning calorimetry (DSC) supported by FT-IR analyses in order to point out the solid-state interaction between the two components. Phase solubility studies were performed according to Higuchi and Connors method, with a concentration of CD ranging from 0 to 200 mM. Stability studies have been performed in order to verify how much the presence of CD can influence the degradation process of the drug; the results within 14 days showed that the binary systems slowed down the DMF degradation process. Solutions of DMF and the kneading products were freeze-dried, according to a design of experiment plan, to evaluate the effect of complexation on relevant stability aspects and quantify the presence of degradation products monomethyl fumarate and fumaric acid. RAMEB:DMF at 2:1 molar ratio seemed the most suitable system for DMF stabilization. The present work highlights how CDs can be a valid tool to increase the water solubility and stability of the drug, with interesting perspectives in relation to a possible nasal application.
Relapsing-remitting multiple sclerosis is a chronic inflammatory disease of the central nervous s... more Relapsing-remitting multiple sclerosis is a chronic inflammatory disease of the central nervous system. Solid dosage forms in capsules of dimethyl fumarate (DMF) are currently used as first line treatment [1], [2]. However, the gastrointestinal side effects, the limited solubility and the low stability, limit its therapeutic efficacy. To overcome this issues, binary systems of DMF and semisynthetic derivatives of β-cyclodextrin (β-CD), in particular hydroxypropyl (HPβCD) and randomly methylated β-CD (RAMEB) were prepared with the aim to improve its bioavailability and allow its administration by the nasal route [3]. Complexes by kneading method, at 1:1 and 1:2 molar ratios, were prepared and characterized by means of differential scanning calorimetry (DSC) supported by FT-IR analyses in order to point out the solid-state interaction between the two components. Phase solubility studies were performed according to Higuchi and Connors method, with a concentration of CD ranging from 0 to 200 mM. Stability studies have been performed in order to verify how much the presence of CD can influence the degradation process of the drug; the results within 14 days showed that the binary systems slowed down the DMF degradation process. Solutions of DMF and the kneading products were freeze-dried, according to a design of experiment plan, to evaluate the effect of complexation on relevant stability aspects and quantify the presence of degradation products monomethyl fumarate and fumaric acid. RAMEB:DMF at 2:1 molar ratio seemed the most suitable system for DMF stabilization. The present work highlights how CDs can be a valid tool to increase the water solubility and stability of the drug, with interesting perspectives in relation to a possible nasal application.
V. Symposium of Young Researchers on Pharmaceutical Technology, Biotechnology and Regulatory Science, 2023
Relapsing-remitting multiple sclerosis is a chronic inflammatory disease of the central nervous s... more Relapsing-remitting multiple sclerosis is a chronic inflammatory disease of the central nervous system. Solid dosage forms in capsules of dimethyl fumarate (DMF) are currently used as first line treatment [1], [2]. However, the gastrointestinal side effects, the limited solubility and the low stability, limit its therapeutic efficacy. To overcome this issues, binary systems of DMF and semisynthetic derivatives of β-cyclodextrin (β-CD), in particular hydroxypropyl (HPβCD) and randomly methylated β-CD (RAMEB) were prepared with the aim to improve its bioavailability and allow its administration by the nasal route [3]. Complexes by kneading method, at 1:1 and 1:2 molar ratios, were prepared and characterized by means of differential scanning calorimetry (DSC) supported by FT-IR analyses in order to point out the solid-state interaction between the two components. Phase solubility studies were performed according to Higuchi and Connors method, with a concentration of CD ranging from 0 to 200 mM. Stability studies have been performed in order to verify how much the presence of CD can influence the degradation process of the drug; the results within 14 days showed that the binary systems slowed down the DMF degradation process. Solutions of DMF and the kneading products were freeze-dried, according to a design of experiment plan, to evaluate the effect of complexation on relevant stability aspects and quantify the presence of degradation products monomethyl fumarate and fumaric acid. RAMEB:DMF at 2:1 molar ratio seemed the most suitable system for DMF stabilization. The present work highlights how CDs can be a valid tool to increase the water solubility and stability of the drug, with interesting perspectives in relation to a possible nasal application.
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Papers by Eleonora Cama