Enhanced pharmacological efficacy of sumatriptan due to modification of its physicochemical properties by inclusion in selected cyclodextrins

Abstract

The study focused on the pharmacological action of sumatriptan, in particular its antiallodynic and antihyperalgesic properties, as an effect of cyclodextrinic inclusion of sumatriptan, resulting in changes of its physicochemical qualities such as dissolution and permeability through artificial biological membranes, which had previously been examined in vitro in a gastro-intestinal model. The inclusion of sumatriptan into β-cyclodextrin and 2-hydroxylpropylo-β-cyclodextrin by kneading was confirmed with the use of spectral (fourier-transform infrared spectroscopy (FT-IR); solid state nuclear magnetic resonance spectroscopy with magic angle spinning condition, 1H and 13C MAS NMR) and thermal (differential scanning calorimetry (DSC)) methods. A precise indication of the domains of sumatriptan responsible for its interaction with cyclodextrin cavities was possible due to a theoretical approach to the analysis of experimental spectra. A high-performance liquid chromatography with a diode-array detector method (HPLC-DAD) was employed to determine changes in the concentration of sumatriptan during dissolution and permeability experiments. The inclusion of sumatriptan in complex with cyclodextrins was found to significantly modify its dissolution profiles by increasing the concentration of sumatriptan in complexed form in an acceptor solution compared to in its free form. Following complexation, sumatriptan manifested an enhanced ability to permeate through artificial biological membranes in a gastro-intestinal model for both cyclodextrins at all pH values. As a consequence of the greater permeability of sumatriptan and its increased dissolution from the complexes, an improved pharmacological response was observed when cyclodextrin complexes were applied.

Computer-Aided Design of Cefuroxime Axetil/Cyclodextrin System with Enhanced Solubility and Antimicrobial Activity

“…The eligibility of certain kinds of cyclodextrin to achieve the desired stability of the system in solution is determined by the structure of CD and guest API [13]. The thermodynamic effect described by Gibbs free energy of complex formation, as well as by entailed stability constant Ks, can be estimated by structure-based modeling with in silico methods [11,12,[14][15][16][17][18]. Application of theoretical approaches, considering a vast number of testable cyclodextrin derivatives, is an essential tool for streamlining experimental investigation.…”

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

“…[50][51][52] In our previous studies, we also confirmed that an increase in the analgesic effect for sumatriptan after introduction into CD structures was possible. 23 Other studies confirming the beneficial impact of CD systems on the analgesic effect were also obtained in the case of ketoprofen, where antipyretic, analgesic and anti-inflammatory effects increased, and in the mice study for meloxicam, where the elevated API serum levels maximized its analgesic activity. 53,54 The strengths of the studies performed include increasing the solubility of TA with a method that can be easily used in the preparation of a drug form for patients.…”

“…To induce migraine-like pain, nitroglycerin (NTG) (Perlinganit, 1mg/1mL, UCB Pharma GmbH, Germany) was administered by the intraperitoneal route 60 min before further behavioral tests. 23 Behavioral tests were performed at the Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College in Cracow, Poland. In in vivo tests, 63 adult male Albino Swiss (CD-1) mice weighing between 18 and 22 g were used.…”

“…Based on our previous research measurements were collected before NTG administration (referred to as "before nitroglycerin"), 60 min after its injection (baseline, pre-drug measurements), and then, 60 min after TA systems administration (post-drug measurements). 23 This time point for measuring post-drug effects of TA forms was selected based on the available literature data which showed that for TA used orally the mean time to reach the peak plasma concentration (T max ) was approx.1 h. 30 Assessment of Tactile Allodynia -Von Frey Test Mechanical hypersensitivity (tactile allodynia) in mice was assessed using the electronic von Frey unit (Bioseb, France). 31 This device is supplied with a single flexible filament applying increasing force (from 0 to 10 g) against the plantar surface of the hind paw of a mouse.…”

“…The infusion of NTG in mice caused thermal and mechanical allodynia, and these symptoms were reversed by sumatriptan. 23 Moreover, some studies showed that NTG-treated mice developed aversion to light and increased meningeal blood flow and this mouse model was also used to study the progression of the disorder from an acute to a chronic condition. Taken together, this NTG model may be considered as a "gold standard" and a reliable screening tool in the search for novel therapies in migraine treatment.…”