In situ gels have been developed as an innovative strategy to prolong corneal residence time and enhance drug absorption compared to traditional eye drops. Our study aimed to formulate an ophthalmic in situ gel with a combination of two thermosensitive poloxamers, P407 and P188, in an optimal ratio not only to increase the time of action but also to increase the solubility of selected antibiotics for the treatment of ophthalmic infections. Two BSC II class substances, Azithromycin and Ofloxacin, with different mechanisms of action, have been incorporated into the in situ gel system after determining their solubility. The antibiotics-loaded in situ gel formulation was evaluated for its clarity, pH, rheological properties, and gel characteristics of gelling time, temperature, and capacity. The formulation demonstrated satisfactory clarity, appropriate pH, effective gelation properties in simulated tear fluid, and suitable rheological characteristics. In addition, APIs release insight has been studied through a dissolution test, and the effectivity against sensitive and resistant bacterial strains has been proved through the antimicrobial study. Therefore, our in situ gel system based on thermosensitive poloxamers, with two hydrophobic antibiotics, AZM and OFX, can be considered a valuable approach for ophthalmic drug delivery with an enhancement of the antibiotics bioavailability through increasing the contact time with the ocular surface and enhancing patient compliance.

Background: Menopause is characterised by a decline in oestrogen levels, leading to physical and psychological symptoms that significantly affect quality of life. Current parenteral oestradiol ester therapies, while effective, are often associated with side effects due to their oil-based formulations, including injection-site reactions and immune responses. Methods: In this study, we developed a water-soluble, polyethylene glycol cross-linked β-cyclodextrin (PEG–β-CD) polymer-based system for parenteral oestradiol delivery and evaluated its biocompatibility, solubility enhancement, immune compatibility, and pharmacokinetics. Results: Cytotoxicity assays using NIH-3T3 fibroblasts and RAW 264.7 macrophages showed minimal toxicity up to 10% (w/w). Phase-solubility studies demonstrated a significant increase in oestradiol solubility with the PEG–β-CD polymer, surpassing that of β-cyclodextrin or PEG alone. Dynamic light scattering and FTIR analyses confirmed successful complex formation, with submicron particles averaging 271 nm and physical incorporation of oestradiol into the polymer matrix. Macrophage activation assays and RT-qPCR analyses indicated an absence of immunogenic responses or pro-inflammatory cytokine induction. In vivo toxicity testing in Galleria mellonella larvae confirmed safety, while pharmacokinetic studies in Wistar rats revealed rapid initial absorption followed by stable, low-level serum concentrations comparable to those of commercially used oestradiol esters. Conclusions: These findings indicate that the PEG–β-CD polymer–oestradiol complex provides a safe, water-based alternative to traditional oil-based injections, with the potential to reduce side effects and improve patient compliance in postmenopausal hormone therapy.

Background: Buccal films have attracted continued interest due to their several advantages. However, developing effective buccal films for hydrophilic drugs remains challenging due to limited buccal permeability. Captopril, a water-soluble ACEI, represents a suitable model for evaluating buccal films. Chitosan–ascorbate has previously been studied in solution for its cytotoxicity and permeation-enhancing properties. However, its performance as a buccal-film dosage form requires further investigation. The present study extends earlier formulation work by evaluating the in vitro cytotoxicity, permeability, and stability of captopril-loaded chitosan–ascorbate buccal films. Methods: Blank and captopril-loaded films were assessed. Cytotoxicity and permeability were evaluated using TR146 cells and compared with chitosan–acetate films as a reference. Accelerated stability test (40 °C/75% RH, three months) was performed to monitor moisture content, mechanical properties, and drug content. FT-IR spectroscopy was used to investigate potential chemical interactions. Results: All films maintained cell viability above 80%. Chitosan–ascorbate films significantly increased captopril permeation compared with chitosan–acetate films, achieving up to a 12–16-fold increase in cumulative drug permeation. The stability test did not reveal any new chemical reactions or interactions based on FT-IR analysis, indicating that the polymer system remained structurally stable; however, it showed continuous moisture uptake, slight deterioration of mechanical properties and a decrease in drug content. Conclusions: This study provides an in vitro, dosage-form–level evaluation of captopril-loaded chitosan–ascorbate buccal films, demonstrating acceptable cytocompatibility and moderate enhancement of permeability. However, significant moisture sensitivity under accelerated conditions can represent limitations, highlighting the importance of protective packaging or further formulation optimization to overcome this.

Background/Objectives: The buccal mucosa offers a promising non-invasive route for systemic drug delivery, particularly for hydrophilic compounds like captopril (CAP), which exhibit low permeability and are subject to gastrointestinal instability and first-pass metabolism. This study aimed to develop and characterize captopril-loaded, chitosan-based mucoadhesive buccal films with different permeation enhancers and to evaluate their physicochemical properties, drug release, cytocompatibility, and in vitro transport across a TR146 buccal epithelial cell model. Methods: Films were prepared by the solvent-casting method using chitosan as the film-forming polymer. Different enhancers were investigated, including organic acid salts of chitosan (ascorbate, citrate, and lactate) and chemical permeation enhancers (sodium lauryl sulfate, polyethylene glycol 400, Span 20, and EDTA). Results: The resulting films exhibited acceptable thickness, moisture content, appropriate mechanical properties, and good mucoadhesive strength. In vitro dissolution studies demonstrated rapid CAP release, with >50% released within 15 min and near-complete release by 180 min across all formulations. Cytotoxicity assessment via a Neutral Red uptake assay in TR146 cells confirmed high cell viability (>81%) after 4 h of exposure, indicating good biocompatibility. In vitro permeation experiments revealed that films prepared with chitosan ascorbate and chitosan lactate enhanced CAP transport compared to other formulations, achieving the highest flux and apparent permeability coefficients. Conclusions: These findings demonstrate that chitosan ascorbate and lactate salts effectively improve the buccal permeability of captopril while maintaining good film properties and biocompatibility. This work highlights the potential of chitosan ascorbate- and lactate-based mucoadhesive films as an efficient platform for the buccal delivery of CAP.