Study of the effect of active pharmaceutical ingredients of various classes of BCS on the parameters of thermosensitive systems based on poloxamers.

Introduction: The development of thermosensitive in situ systems has become widespread and prospective due to the optimal parameters of the phase transition - in the temperature range from room to physiological. Those properties can provide thermosensitive polymers, for example, poloxamers - as the most common.It is worth noting that the addition of active pharmaceutical ingredients (APIs) changes the parameters of in situ systems, but no systematic study of the effect of APIs has been conducted. The aim of this work was to develop a systematic approach to studying the effect of APIs on the in situ rheological properties of poloxamer compositions. Materials and methods: The biopharmaceutical classification system (BCS) was chosen as the basis. Accordingly, the following APIs were selected for the experiment: BCS class I - lidocaine hydrochloride and ketorolac tromethamine, class II - ibuprofen and diclofenac, class III - pyridoxine hydrochloride and ribavirin, class IV - furosemide and abiraterone. To create thermoreversible compositions, previously studied for stability combinations of poloxamer 407, poloxamer 188 and PEG 1500 were used.At the stage of preparation of experimental samples formulations with APIs of classes II and IV of BCS were excluded, since the solubilizing ability of poloxamers is not enough to obtain stable combined complexes. Results: In the course of the work, the following results were obtained: BCS class I APIs significantly reduced the phase transition temperature of the matrix of poloxamers 407 and 188, while the addition of PEG 1500 eliminated the effect of APIs on gels; BCS class III APIs practically did not affect the rheological properties of the studied combinations; the phase transition temperature of the gel based on poloxamer 407 did not change with the addition of Class I and Class III APIs.Nevertheless, the obtained results made it possible to reveal the regular behavior of in situ complexes of poloxamer matrices depending on the class of BCS of the API. Further research is required.

Development of In Situ Intranasal System Based on Chitosan Formate.

We studied the potential of using a salt form of chitosan as a pH-sensitive in situ matrix. Among common chitosan salts obtained by heterogeneous synthesis, chitosan formate exhibiting the highest pH-sensitivity was selected. However, the low mucoadhesion strength of the composition, as well as high pH required for the phase transition necessitate designing a polycomponent compound with a poloxamer to additionally provide a thermosensitive phase transition. Compared with the use of pure poloxamer, the chitosan complex demonstrated improved mucoadhesion in in vitro studies, and the phase transition parameters were optimal for intranasal administration. An in vivo study revealed no locally irritating effect of the composition, which allows its further development.

[In situ gels as a modern method of intranasal vaccine delivery].

The continuous emergence of new pathogens and the evolution of microbial drug resistance make it absolutely necessary to develop innovative, effective vaccination strategies. Use of nasal vaccination can increase convenience, safety, cause both local and systemic immune reactions. Intranasal administration nevertheless has a number of shortcomings that can be overcome by using the latest achievements of pharmaceutical science. One of the aspects of such solution may be the use of systems for the production of intranasal vaccines in situ polymer compositions that provide a directed sol-gel transition controlled by the physiological conditions of the nasal cavity. At the same time, the gelation of the administered dose in contact with the nasal mucosa involves prolonged exposure of the drug at the injection site, greater mucoadhesion, counteraction to mucociliary clearance, modified and more complete release. A number of both foreign and domestic manufacturers produces polymers such as chitosan, gums, polyoxyethylene and polyoxypropylene block copolymers (poloxamers, proxanols), carbomers. For effective pharmaceutical development of new intranasal IBD delivery systems corresponding to the QbD concept, not only the knowledge of the range of excipients is necessary, but also simple, accessible, and reproducible methods for determining indicators that define the critical parameters of such delivery systems. In accordance with the conducted scientific search, the main indicators of standardization of in situ intranasal systems were identified: temperature and time of gel formation, gel strength, rheological characteristics, mucoadhesion, release, nasal mucociliary clearance time.

Determination of Bactericidal Activity Spectrum of Recombinant Endolysins of ECD7, Am24, Ap22, Si3, and St11 Bacteriophages.

The bactericidal activity of recombinant endolysins LysECD7, LysAm24, LysAp22, LysSi3 and LysSt11 was assayed in multidrug resistant strains (n=120) of Salmonella enterica, E. coli, Acinetobacter baumannii, Enterobacter spp., Pseudomonas aeruginosa, Klebsiella pneumoniae, and Campylobacter jejuni. The assay showed that the recombinant endolysins had a wide spectrum of bactericidal activity compared to endolysins of their progenitor phages. Among examined endolysins, we selected the active pharmaceutical substances with broad spectrum of bactericidal activity. Most strains were sensitive to LysECD7 (70.7%), LysAm24 (65%), and LysAp22 (58.6%), which seems to be promising causative agents for the development of finished dosage form.

Analysis of the Pharmacokinetics of Suppository Forms of Bacteriophages.

Pharmacokinetics of suppository forms of bacteriophages was studied on male Chinchilla rabbits. Suppositories with various composition of bacteriophages were administered once per rectum to rabbits, and the presence of phage particles was estimated in the blood, urine, and feces over 24 h. Pharmacokinetic study showed that the phages were detected in the blood, urine, and feces at various terms of the experiment irrespective of the size of viral particles, which confirmed the possibility of their systemic effects after rectal administration. Thus, the use of suppository form of bacteriophages can ensure the presence of phage particles even in infection foci that cannot directly contact with the preparation.

New Combined Eye Gel with Alpha-2-Beta Interferon.

The results of the development of combined eye gel with interferon alpha-2-beta are presented. Experimental samples of the gel based on different gelling agents were prepared and their biotechnological and technological characteristics (the absence of the cytotoxic effect, aggregation stability, osmotic activity, bioadhesion, and rheological parameters) were evaluated. The composition with hydroxyethyl cellulose, Natrosol 250HHX, in a concentration of 1.5% as a gelling agent showed the best results and the best one-year stability.