(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.

Abnormal corneal wound healing can compromise corneal transparency and lead to visual impairment. Mineralocorticoid receptor antagonists (MRA) are promising candidates to promote corneal remodeling with anti-inflammatory properties and lack gluococorticoids-associated side effects. In this preclinical study, a new polymer-free hydroxypropyl-gamma-cyclodextrin-based eyedrop containing 0.1% spironolactone (SPL), a potent but non-water-soluble MRA, was investigated for its ocular surface tolerance and efficacy in a rat model of corneal wound healing. SPL eyedrops were stable for up to 9 months at 4 °C. The formulation was well-tolerated since no morphological changes or inflammatory reactions were observed in the rat cornea after multiple daily instillations over 7 days. SPL eyedrops accelerated rat corneal wound healing, reduced corneal edema and inflammation, enhanced epithelial integrity, and improved nerve regeneration, suggesting restoration of corneal homeostasis, while potassium canrenoate, an active and soluble metabolite of SPL, had no effect. SPL eyedrops could benefit patients with impaired corneal wound healing, including that secondary to glucocorticoid therapy. Repurposing known drugs with known excipients will expedite translation to the clinic.

Hydroxychloroquine is an antimalarial drug indicated in the treatment of acute attacks of malaria due to Plasmodium vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum. It is also used for the treatment of rheumatoid arthritis, discoid and systemic lupus erythematosus, and more recently proposed in COVID-19 therapy. Hydroxychloroquine is only available in tablets which are not easy to administer for pediatric and geriatric patients, and patients unable to swallow such as patients found in intensive care units. The aim of this work was to develop and optimize a ready to use liquid hydroxychloroquine formulation and to carry out the corresponding chemical and microbiological stability studies. The formulation was evaluated for ease of preparation, physical properties, and palatability. Its stability was performed at ambient temperature and under refrigeration. After 6 months of stability testing, the results showed no pH change, no drug loss, no microbial development, and no visual change. The formulation, employing excipients in a range that EMA has recommended, showed chemical and microbiological stability for at least 6 months even in the worst storage conditions.

La carcinose péritonéale a longtemps été considérée comme le stade terminal des cancers colorectaux, ne laissant place qu'à des soins palliatifs. Aujourd'hui, l'association de la chirurgie de cytoréduction et de la chimiothérapie intrapéritonéale a considérablement amélioré le pronostic des patients. La chirurgie permet l'ablation macroscopique des cellules tumorales, tandis que la chimiothérapie locale vise à éliminer les cellules résiduelles après la résection. Cependant, l'efficacité de la chimiothérapie hyperthermique intrapéritonéale est limitée par la faible pénétration des agents cytotoxiques dans les tissus. De plus, aucun traitement prophylactique spécifiquement conçu pour prévenir l'implantation péritonéale n'est actuellement disponible, malgré l'existence de situations à risque. L'objectif de ce travail était de développer une formulation permettant une distribution homogène dans la cavité péritonéale et une libération prolongée de la chimiothérapie, afin d'en optimiser l'efficacité. Un hydrogel thermosensible à base de poloxamères a été mis au point. Une étude préliminaire, réalisée sur un modèle porcin, a permis d'évaluer la distribution de l'hydrogel dans la cavité abdominale, sa toxicité, ainsi que la cinétique de libération de l'oxaliplatine. La toxicité élevée de l'oxaliplatine et l'évolution des recommandations cliniques récentes, ont réorienté l'étude vers la mitomycine. Une seconde phase de recherche s'est orientée vers l'optimisation des propriétés de l'hydrogel pour ralentir la libération du principe actif. Pour cela, le poloxamère 407 a été associé à différents polymères, et l'impact sur les propriétés rhéologiques de l'hydrogel et sur le temps de dissolution de l'hydrogel a été étudié à l'aide de plans d'expériences. Cette démarche a permis d'identifier une formulation optimale de mitomycine permettant une libération plus prolongée. Enfin, pour limiter le passage systémique de cette molécule hydrophile de petite taille, son encapsulation dans des microparticules polymériques a été envisagée. Des microparticules composées d'acide poly(lactique-co-glycolique) (PLGA) ont ainsi été préparées selon la méthode de la double émulsion suivie d'une évaporation de solvant.