Effects of Cogrinding with β-Cyclodextrin on the Solid State Fentanyl

Sufentanil–2‐Hydroxypropyl‐β‐Cyclodextrin Inclusion Complex for pain Treatment: Physicochemical, Cytotoxicity, and Pharmacological Evaluation

“…CDs are able to form inclusion (host–guest) complexes with a variety of organic molecules, the so‐called guest molecules 3. Inclusion complexes between opioids and CDs have been described,4–8 showing an increased duration of analgesia after using hydroxypropyl‐β‐CD as a vehicle for intrathecal administration. Since then, several studies have described a modulation of opioid release (morphine, fentanyl, and SUF) after complexation with CDs, especially after intrathecal administration 4,5.…”

“…In addition, Meert and Melis6 observed an increase in the duration of analgesia by intrathecal combination of complexed SUF (hydroxypropyl‐β‐CD) with the local anesthetic bupivacaine. Only few reports described the physicochemical characterization of opioids (fentanyl) in CDs7,8; however, intramuscular administration was not considered for the development of those studies.…”

Interaction of fentanyl with various cyclodextrins in aqueous solutions

“…1 H‐NMR is a well‐known analytical method that provides direct information regarding the complex structure via comparisons of the proton chemical shifts observed for the host–guest mixture with those observed for individual species. In this study, the NMR spectra of β‐CD, G1‐β‐CD, fentanyl base and fentanyl citrate were assigned on the basis of 1 H‐, 13 C‐ and two‐dimensional NMR measurements; the theoretical calculations; and the NMR spectral literature data of the compounds [17,20,32–35]. Figure presents the 1 H‐NMR spectra of the mixture of fentanyl citrate and G1‐β‐CD (a), the mixture of fentanyl citrate and β‐CD (b), and fentanyl citrate (c) at 0.7–3.2 (I) and 7.0–7.5 ppm (II).…”

“…As previously mentioned, we focused on CDs as pharmaceutical additives for improving the solubility or dispersibility of fentanyl base. Previously, we evaluated the solid‐state interaction between β‐CD and fentanyl base and revealed the cogrinding effect with β‐CD on the dispersion and inclusion of fentanyl base [17]. Therefore, in this study, the effect of CDs on fentanyl base in the solution was evaluated.…”

Physicochemical Characterization of Cyclodextrin–Drug Interactions in the Solid State and the Effect of Water on These Interactions

“…In association with solid‐state CD–drug interactions under humidified conditions, the physicochemical characteristics of ground and humidified mixtures of fentanyl base (Fig. b)—a highly potent and clinically used narcotic analgesic—and β‐CD were studied at β‐CD–fentanyl molar ratios of 1:1 and 2:1 . Ground mixtures were prepared using a desktop ball mill at 25°C and humidified by exposure to 85% RH at 30°C.…”