Development of Thermosensitive and Mucoadhesive Hydrogel for Buccal Delivery of (S)-Ketamine

Abstract

(S)-ketamine presents potential for the management of acute pain and, more specifically, for the prevention of pain associated with care. However, the administration route can be a source of pain and distress. In this context, a smart formulation of (S)-ketamine was designed for buccal administration. The combination of poloxamer 407 and sodium alginate enables increased contact with mucosa components (mucins) to improve the absorption of (S)-ketamine. In this study, rheological studies allowed us to define the concentration of P407 to obtain a gelling temperature around 32 °C. Mucoadhesion tests by the synergism method were carried out to determine the most suitable alginate among three grades and its quantity to optimize its mucoadhesive properties. Protanal LF 10/60 was found to be the most effective in achieving interaction with mucins in simulated saliva fluid. P407 and alginate concentrations were set to 16% and 0.1%. Then, the impact of P407 batches was also studied and significant batch-to-batch variability in rheological properties was observed. However, in vitro drug release studies demonstrated that this variability has no significant impact on the drug release profile. This optimized formulation has fast release, which provides potential clinical interest, particularly in emergencies.

Growth Factors-Loaded Temperature-Sensitive Hydrogel as Biomimetic Mucus Attenuated Murine Ulcerative Colitis via Repairing the Mucosal Barriers

“…17% (w/v), which is usually not resistant to water dilution when applied in mucosal tissue. 28 To overcome this drawback, DAP has been successfully synthesized in our previous study. 14 DAP not only retains the thermosensitive property of P407 but also presents tougher mechanical strength and stronger tissue adhesion.…”

“…Among the variants of poloxamers, P407 is widely used as a hydrogel-forming material owing to its low toxicity and high solubility in water; P407 has the lowest hydrogel-forming concentration of ca. 17% (w/v), which is usually not resistant to water dilution when applied in mucosal tissue . To overcome this drawback, DAP has been successfully synthesized in our previous study .…”

Recent progress in thermosensitive hydrogels and their applications in drug delivery area

“…Furthermore, the synthesized formulation showed a promising in vitro drug-releasing profile and demonstrated high bioavailability with the fast release. 67 Yan et al reported the hybrid hydrogel of corn fiber gum and soya bean protein to deliver the thermosensitive bioactive components orally. The thermosensitive model component was riboflavin (Vitamin B2).…”

“…The selection of appropriate thermosensitive polymer for gelling temperature (32°C) based on the rheological studies of poloxamer 407. Furthermore, the synthesized formulation showed a promising in vitro drug‐releasing profile and demonstrated high bioavailability with the fast release 67 . Yan et al reported the hybrid hydrogel of corn fiber gum and soya bean protein to deliver the thermosensitive bioactive components orally.…”