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.

[The development of the physicochemical characteristics of the new original nootropic substance TST-9]. / Izuchenie fiziko-khimicheskikh svoistv novogo original'nogo nootropnogo sredstva TST-9.

Physicochemical properties of the original pharmaceutical substance TST-9 based on the 3,7-diazabicyclo[3.3.1]nonane derivative with the chemical name IUPAC 6-[4methoxy-3-(1H-pyrazol-1-ylmethyl) benzyl]-1,11-dimethyl-3,6,9-triazatricyclo[7.3.1.1]tetradecane-4,8,12-trion, were studied. TST-9 is used as an active substance for the development of the composition and technology for the preparation of an innovative oral drug. The pharmaceutical substance TST-9 is an amorphous white powder, odorless, soluble in chloroform, acetonitrile, methylene chloride, acetone, dimethyl sulfoxide, dimethylformamide and alcohol, sparingly soluble in diethyl ether, dioxane and is very slightly soluble in water, hexane, and heptane. The melting point ranged from 94°C to 96°C without visible decomposition of the substance. The microbiological purity corresponds to category 2.2. Residual organic solvents in the form of chloroform did not exceed 0.006%. The amount of impurities was not more than 0.15%. The loss in mass upon drying was not more than 0.5%. The "identity" was confirmed using nuclear magnetic resonance spectroscopy and HPLC with UV detection. The data obtained in the study will contribute to the further development of the dosage form, the choice of the route of administration and the dosage regimen, as well as the selection of analytical methods for analyzing the quality of the finished dosage form and the effective, high-precision determination of the content of the active substance and its likely decay products.

[Application of adhesive compositions in surgery (in Russian only)]. / Primenenie kleevykh kompozitsii v khirurgii.

New adhesive compositions will almost completely prevent leakage of surgical sutures and undue tissue damage, improve healing and postoperative rehabilitation. At present time there is no universal type of bioadhesives that is suitable for all tissues and types of sutures because of various surgeries and their specificity. The article describes the advantages and disadvantages of all common types of bioadhesives, as well as the ways to overcome their disadvantages.