ABSTRACT
The main method of treatment and prevention of endophthalmitis is a combination of intravitreal and topical administration of antibiotics, such as cefuroxime moxifloxacin or vancomycin. However, this method is ineffective due to the rapid elimination of the drug. This problem can be solved with the help of intravitreal in situ injection systems, which are injected with a syringe into the vitreous body and provide prolonged action of the drug at the focus of inflammation. Under the influence of temperature, the liquid drug undergoes a phase transition and turns into a gel after injection. This ensures its prolonged action. The study aimed to develop an intravitreal in situ cefuroxime delivery system for the treatment of endophthalmitis based on a thermosensitive biodegradable composition of poloxamer 407 and hyaluronic acid. A combination of poloxamer Kolliphor® P407, Kolliphor® P188, and PrincipHYAL® hyaluronic acids of different molecular weights was used as a delivery system. The potency of cefuroxime solid dispersion with polyvinylpyrrolidone-10000, polyethylene glycol-400, and polyethylene glycol-1500 in a 1:2 ratio was studied for prolonged action compared to cefuroxime substance. The experimental formulations were studied for the parameters of gelation temperature in a long-term test (4 months), pH, and release of cefuroxime using dialysis bags. To study the distribution parameter in the vitreous body, an in vitro model (1/13) was developed, which was a hollow agar sphere filled with 1% (w/v) polyacrylate gel. For the superior formulations, a HET-CAM test (chorioallantoic membrane test) was performed to determine the absence of irritant effects. According to the study results, a formulation containing a solid dispersion of cefuroxime:PEG-400 (1:2), the matrix of which contained 18% (w/v) Kolliphor® P407 poloxamer, 3% (w/v) Kolliphor® P188 poloxamer, and 0.5% (w/v) hyaluronic acid (1400-1800), was selected. This sample had an average gelation temperature of 34.6 °C, pH 6.7 ± 0.5, and a pronounced prolonged effect. Only 7.6% was released in 3 h of the experiment, whereas about 38% of cefuroxime was released in 72 h. No irritant effect on the chorioallantoic membrane was observed for any formulations studied.
ABSTRACT
Thermosensitive systems based on poloxamer 407 are widely used in targeted drug delivery; however, the stability of the phase transition temperature remains insufficiently studied. This article presents the results of a study on the effect of adding polyethylene glycols (PEG) with different molecular weights and some classical gel-forming polymers on the gelation temperature of thermoreversible compositions based on poloxamer 407 in a long-term experiment. The study showed a positive effect of PEG addition with average molecular weights at concentrations of 1.5-2.0%, as well as gelling agents at a concentration below the critical gelation concentration. The proposed rheological test for studying the samples' adhesion can give an indirect forecast of the composition adhesive rate. Based on the conducted studies, three experimental binary systems based on poloxamer 407 were selected, with the addition of HPMC 0.5%, sodium alginate 0.5%, and PEG 1500 1.5%. These systems are the most promising for the further development of in situ targeted drug delivery systems.
ABSTRACT
Spray film-forming systems (SFFSs) provide great potential for the treatment of various types of wounds. Such systems afford to prolong the action of active substances, to prevent cross-contamination, and to ensure accelerated wound healing. Spray films are known since the mid-20th century, and nowadays they are widely used to treat minor skin injuries, but numerous clinical cases describe their successful use in the treatment of burns, wounds, bedsores, etc. The current level of polymer development and composite synthesis has greatly expanded the possibilities of creating compositions of spray film-forming systems. Scattered information and lack of standardization of such delivery systems creates difficulties for pharmaceutical development. This review highlights most of the existing requirements and suggestions from studies to standardize the characteristics of SFFSs and classify them based on scientific sources and regulatory documentation, as well as the position of such systems in the pharmaceutical market. The search and evaluation of known characterization methods and their modifications, as well as the approval of their list (separately for development and for standardization) can potentially increase the research interest in the problem of spray film-forming systems development and contribute to the registration of new drugs and medical devices in this promising dosage form, including with its own pharmacological effect.
