Poor bioavailability of eye drops is a well-known issue, which can be improved by increasing the residence time on the eye surface and the penetration of the active pharmaceutical ingredient (API). This study aims to formulate in situ gelling mucoadhesive ophthalmic preparations. To increase the residence time, the formulations were based on a thermosensitive polymer (Poloxamer 407 (P407)) and were combined with two types of mucoadhesive polymers. Dexamethasone (DXM) was solubilized by complexation with cyclodextrins (CD). The effect of the composition on the gel structure, mucoadhesion, dissolution, and permeability was investigated with 3³ full factorial design. These parameters of the gels were measured by rheological studies, tensile test, dialysis membrane diffusion, and in vitro permeability assay. The dissolution and permeability of the gels were also compared with DXM suspension and CD-DXM solution. The gelation is strongly determined by P407; however, the mucoadhesive polymers also influenced it. Mucoadhesion increased with the polymer concentration. The first phase of drug release was similar to that of the CD-DXM solution, then it became prolonged. The permeability of DXM was significantly improved. The factorial design helped to identify the most important factors, thereby facilitating the formulation of a suitable carrier for the CD-DXM complex.

Background/Objectives: This study investigates the use of natural deep eutectic solvents (NADESs) in enhancing the solubility and skin permeation of a lidocaine base, a lipophilic form, in hydrogel systems. The aim was to develop an environmentally sustainable and biocompatible alternative to conventional lidocaine formulations, improving the dermal permeation and therapeutic efficacy. Methods: The lidocaine base was dissolved in a hydrophilic NADES system composed of choline chloride and citric acid, facilitating enhanced solubility, likely through new molecular interactions. Then, pH-adjusted hydrogels were formulated and optimized by employing a 3² full factorial design. Raman and nuclear magnetic resonance (NMR) spectroscopy were applied to evaluate the stability of lidocaine in the optimal formulation. The biopharmaceutical properties were investigated using in vitro drug release and skin permeation studies. In vivo tests assessed physiological skin parameters such as the hydration and transepidermal water loss. Results: The developed NADES-containing hydrogel significantly improved the solubility and stability of lidocaine. Skin permeation studies demonstrated enhanced dermal permeation compared with conventional hydrogel and ointment. These improvements, namely the enhanced solubility of lidocaine in the formulation and its increased permeation, were attributed to the dual effect of the NADES. Conclusions: NADES-containing hydrogels represent a promising green technology for formulating lidocaine-containing dermal preparations. This approach offers a biocompatible, natural-based alternative that can enhance the bioavailability and efficacy of topical anesthetics.

Effective ocular drug delivery is still a challenge for pharmaceutical technologists due to the complex elimination mechanisms of the eye. In situ gels and polymeric micelles are among the pharmaceutical technologies that may enable us to overcome these challenges. Therefore, the objective of this study was to evaluate the ocular applicability of in situ gels and polymeric micelles, as well as their combinations, containing a steroidal anti-inflammatory drug, dexamethasone. The developed formulations were compared on the basis of their physicochemical characteristics, rheological behavior, mucoadhesion, in vitro drug release profile, and in vitro and ex vivo permeability. The developed formulations exhibited moderate stability according to the zeta potential measurements; however, they demonstrated appropriate mucoadhesion and sustained drug release. Furthermore, the results of the permeability studies suggest that combining thermoresponsive in situ gels and polymeric micelles represents a promising strategy for enhancing the therapeutic efficacy of ocular drug delivery.