Controlled release ibuprofen-poloxamer gel for epidural use – A pharmacokinetic study using microdialysis in pigs

Abstract

In order to avoid the risks of sideeffects of epidural local anesthetics and opioids, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) epidurally would be an interesting option of analgesic therapy. The fairly short duration of action of spinally administered NSAIDs, e.g., ibuprofen, may be prolonged by using controlled release poloxamer gel formulation. Using a microdialysis technique we studied the epidural and intrathecal pharmacokinetics of ibuprofen after its epidural administration as a poloxamer 407 formulation or a solution formulation. In addition, plasma ibuprofen concentrations were analyzed from central venous blood samples. Ibuprofen concentrations in the epidural space were significantly higher and longer lasting after the epidural gel injection compared with the epidural solution injection. The epidural AUC of ibuprofen was over threefold greater after epidural ibuprofen gel injection compared with the ibuprofen solution injection (p<0.001). The systemic absorption of ibuprofen from 25% poloxamer 407 gel was very low. The in situ forming poloxamer gel acted as a reservoir allowing targeted ibuprofen release at the epidural injection site and restricted ibuprofen molecules to a smaller spinal area. Ibuprofen diffusion from the epidural space to the intrathecal space was steady and prolonged. These results demonstrate that the use of epidurally injectable poloxamer gel can increase and prolong ibuprofen delivery from epidural space to the CSF enhancing thus ibuprofen entry into the central neuroaxis for spinal analgesia. Further toxicological and dose-finding studies are justified.

Thermoresponsive Hemostatic Hydrogel with a Biomimetic Nanostructure Constructed from Aggregated Collagen Nanofibers

“…The XRD pattern of TS-Gel-Ag-col under different F-107 dosages showed only the diffraction peaks of F-107 (Figure d). Two strong and sharp crystallization peaks, which, respectively, represent the repeating monomer structure of the F-107 molecules in the horizontal and vertical directions, appeared at about 19 and 23°, in agreement with the literature. , Significantly, the amorphous diffraction peaks of Aggregated-col were not observed, possibly because F-107 may completely wrap the fiber surface of Aggregated-col because of its high concentration in the gel, which further confirmed that F-107 was not chemically bonded to Aggregated-col.…”

Localized and targeted delivery of NSAIDs for treatment of inflammation: A review

“…In cases where the vehicle is small enough and has a low enough viscosity to pass through a needle, the introduction of this delivery system to the body is facile (Table 3). [26][27][28][29][30] Typical systems which have these desired properties are nanoparticles or conjugate systems. 26,29,30 While long-term delivery is not required for this type of delivery, it is advantageous as osteoarthritis is the main research focus for this vehicle type.…”

Development and In Vitro Evaluation of Controlled Release Viagra® Containing Poloxamer-188 Using Gastroplus™ PBPK Modeling Software for In Vivo Predictions and Pharmacokinetic Assessments

“…Hydrophilic polymers have been widely applied in drug delivery systems [ 15 ] in form of nanoparticles [ 16 , 17 ], microspheres [ 18 ], self-emulsifying systems [ 19 ], micelles [ 20 , 21 ], cubosomes [ 22 ], ophthalmic formulations [ 23 ], transdermal delivery [ 24 ], nano-solutions [ 25 ], and controlled release matrix formulations [ 26 ]. For example, several studies have been conducted with the hydrophobic polymer P-188 and/or P-407 to develop stable and controlled release dosage formulations for therapeutic agents, including diclofenac sodium [ 26 ], theophylline [ 27 ], methotrexate [ 28 ], morphine [ 29 ], vancomycin [ 30 ], tetramethylpyrazine [ 31 ], indomethacin [ 32 ], ibuprofen [ 33 ], and ketorolac tromethamine [ 34 ]. To the best of our knowledge, no research has been performed yet on developing a controlled release matrix system for SDF using P-188 or another type of polymer.…”