Preparation and assessment of ketamine hydrogels for prolonged transdermal anaesthesia

Purpose: To formulate and assess thermoresponsive ketamine hydrogels for prolonged transdermal analgesia/anaesthesia.
Methods: Thermoresponsive ketamine hydrogels were prepared from chitosan (CTS) and poloxamer 407. Four different formulations (2 formulations of ketamine with 1 and 2 % w/w CTS and 2 formulations with 10 and 15 % w/w ploxamer 407) were assessed for pH, spreadability, drug content, viscosity, in vitro permeation/diffusion, in vivo skin irritancy, and in vivo analgesia (using the hot plate/writhing
method in Wistar rats).
Results: The formulations had a high drug content (96.12 ± 1.24 to 98.49 ± 0.07 %) with good spreadability. They showed prolonged drug release/permeation of ketamine across the skin, ranging from 81.23 to 98.28 %, and were non-irritating to the denuded skin of Wistar rats with no erythema or oedema after 24 h. The preparation showed effective analgesia that lasted 24 to 30 h. In the writhing test, CTS hydrogels showed stronger analgesia (60.26 – 58.97 %) than those made with poloxamerbased hydrogels (56.41 and 53.85 %). Compared to the activity shown by the standard, lidocaine (which produced 62.82 % analgesia), the effect of the test formulations seem good for probable therapeutic use. Using the hot plate method, the poloxamer-based hydrogels showed more prolonged analgesia than the CTS-based hydrogels.
Conclusion: Ketamine hydrogels of CTS and poloxamer may be useful for prolonged analgesia in neuropathic pain and local anaesthesia in minor surgeries.

Keywords
Ketamine; Chitosan; Poloxamer; Thermoresponsive hydrogel; Transdermal; Skin permeation