Details

Autor(en) / Beteiligte

• Stasiłowicz, Anna
• Tykarska, Ewa
• Rosiak, Natalia
• Sałat, Kinga
• Furgała-Wojas, Anna
• Plech, Tomasz
• Lewandowska, Kornelia
• Pikosz, Katarzyna
• Pawłowicz, Kamil
• Cielecka-Piontek, Judyta

Titel

The Inclusion of Tolfenamic Acid into Cyclodextrins Stimulated by Microenvironmental pH Modification as a Way to Increase the Anti-Migraine Effect

Ist Teil von

• Journal of pain research, 2021-01, Vol.14, p.981-992

Ort / Verlag

New Zealand: Dove Medical Press Limited

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The poorly soluble nonsteroidal anti-inflammatory drug (NSAID), tolfenamic acid (TA), was studied to maximize its solubility, permeability through biological membranes, and pharmacological activity. A mixture with magnesium stearate (MS) - microenvironment pH-modifier was prepared, as well as systems additionally containing incorporating substances methyl-β-cyclodextrin (M-β-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). The identification of TA-MS-CD systems was confirmed using experimental methods: X-ray powder diffraction (XRPD) and Fourier transform infrared spectroscopy (FT-IR) with the theoretical support. Apparent solubility study was performed using the paddle apparatus, while in vitro gastrointestinal tract (GIT) and blood-brain barrier (BBB) permeability were conducted by using PAMPA (Parallel Artificial Membrane Permeability Assay). The in vivo part of the study used the mouse nitroglycerin (NTG)-induced migraine pain model. From practically insoluble substance, TA in TA-MS-M-β-CD system dissolved up to 80.13% ± 2.77%, and in TA-MS-HP-β-CD up to 92.39% ± 3.25% in 180 minutes. An increase in TA permeability was also obtained in the TA-MS-M-β-CD and TA-MS-HP-β-CD systems through GIT membranes (P values 2.057 x 10 cm s and 2.091 x 10 cm s , respectively) and through BBB (P values 3.658 x 10 cm s and 3.629 x 10 cm s , respectively). The enlargement of the solubility and permeability impacted analgesia. The dose 25 mg/kg of both TA-MS-HP-β-CD and TA-MS-M-β-CD was almost equally effective and only slightly less effective than the dose 50 mg/kg of pure TA. Both TA-MS-HP-β-CD and TA-MS-M-β-CD used at 50 mg/kg more effectively attenuated tactile allodynia in NTG-treated mice than the same dose of pure TA. None of TA forms influenced heat hyperalgesia. Increasing solubility of TA caused an increase of its analgesic effect in an animal model of migraine pain.