In the perspective of the pharmaceutical industry development, manufacturers expand their product portfolios by updating generic drugs. Complex Generics (CG) or Nonbiological Generic Drugs (NBGD) contain known pharmaceutical substances are out of patent protection and are made by using new technologies, excipients, nanocarriers, dosage form modernization, etc. These drugs are developed in the patients’ interests to improve their life quality and increase drugs’ efficacy and safety. The article discusses the categories and characteristics of CG, shows examples available on the pharmaceutical market, API and dosage forms. This article discusses approaches to quality control that pose challenges for developers and regulators. The fundamental importance of the innovative drugs manufacturing process and the ingredients standardization in the dosage forms formulations to create the standard product are indicated. First, a comprehensive control of polymers is required as an important tool to make the necessary pharmacokinetics. The influence degree on the API release and the effectiveness of dosage form (DF) depends on the polymer’s physicochemical characteristics. In this regard, it is important to create databases of these excipients accessible to developers containing information about properties, use, dosages and safety. In view of the complexity structure and manufacturing processes of the NBGD and insufficiency of pharmacopeial requirements for standard approaches for resolving issues of comparability and bioequivalence the current regulatory documents should be expanded and revise for a correct quality assessment. There is a need to create new scientific and regulatory roadmaps for the development and approval of complex generic drugs.

Introduction. Periprosthetic infections are a major problem in orthopedic surgery. The most optimal way to influence the bacterial film is to suppress the early stages of its formation. The use of hydrogel coatings for the prevention of periprosthetic infections is an effective measure, while the process of coating the implant can be simplified due to the use of in situ systems.Aim. The purpose of the research is to develop and study antibacterial in situ coatings for preoperative treatment of implants.Materials and methods. In the experiment we used poloxamers Kolliphor® P 407 and Kolliphor® P 188 (BASF, Germany), hyaluronic acid high-molecular PrincipHYAL® (1400–1800 kDa), low-molecular PrincipHYAL® (400–600 kDa), mixture of high, medium and low-molecular acids PrincipHYAL® Cube3 (ROELMI HPC Srl, Italy). As screening methods for identifying the optimal composition, we used gelation temperature measurements, pH measurements, studies of rheological properties, and microbiological tests.Results and discussion. During the experiment, we found the optimal concentration of hyaluronic acid 1400–1800 kDa – 0.5 %, at which the studied composition at a temperature of 4.5 ± 0.5 °C was a homogeneous liquid, and it made a sol-gel transition when heated. It was revealed that hyaluronic acid had no significant effect on the gelling temperature, so we added poloxamer 188. We also established the influence of the hyaluronic acid molecular weight on the in situ systems characteristics. High molecular weight hyaluronic acid stabilized the viscosity values and improved the adhesive properties of the system, samples with medium and low molecular weight hyaluronic acid showed lower dynamic viscosity values at the phase gel-sol transition end. We tested the optimal composition (containing 18.0 % poloxamer 407, 2 % poloxamer 188, and 0.5 % hyaluronic acid (1400–1800 kDa) adhesion to the titanium plate. When exposed to the paddle stirrer (rotation speed 20 rpm) for 15 minutes and stored in the thermostat (37,0 ± 0,5 °C) for a week, the analyzed composition showed adhesion strength, which makes it possible to use it for coating.Conclusion. By multistage screening a sample was selected for introduction of a model antibacterial component representing a cocktail of bacteriophages Klebsiella pneumonia, Staphylococcus aureus, Escherichia coli. Microbiological studies showed good compatibility of the immunobiological substance with excipients, which indicated the prospects for further preclinical studies.

Introduction. The problem of pain relief after surgery is relevant in modern dentistry, as pain control is an important part of treatment. In addition to anesthesia, there are other problems of post-resection therapy such as bleeding from the wound and inflammation. Modern dental practice does not have a targeted delivery system or a medical product with analgesic, anti-inflammatory, anesthetic or hemostatic action, which ensures high adherence of patients to the ongoing post-resection therapy.Text. To solve this problem, it can be proposed to develop an in situ implant – a dosage form that is formed directly at the injection site, in the alveolar socket. Targeted delivery system has advantages: no need to use a medical dressing material; no risk of secondary contamination; dosing accuracy and target delivery to the lesion locus; high mucoadhesion to the site of application; the duration of the active ingredient release and others. The purpose of the review is to substantiate the possibility and relevance of developing a new in situ implant system for use in dental post-resection practice. The study was conducted on the main databases of publications (Scopus, Web of Science, PubMed and others), and patent search database on materials published from 2000 to the present. The study describes the currently existing in situ systems for dental problems, which could be a prototype of systems for delivering an anesthetic directly to the tooth socket, the polymers used to create them and the possibility of releasing drugs, and also characterizes existing drugs for the pain relief (applied both locally and for systemic action), in comparison with in situ systems, which have certain advantages and great potential for development.Conclusion. Based on the results of the work, a conclusion about the possibility of pharmaceutical development of dental in situ implants was made, and the most promising polymers for phase transition in the alveolar socket were identified.

N-acetylcysteine (NAC) is a synthetic derivative of L-cysteine, known since the mid-20th century as a mucolytic agent and, in recent decades, has attracted attention for its antioxidant and antibiofilm properties. Bacterial biofilms are structured communities of microorganisms enclosed in an extracellular polymeric matrix, which accounts for their markedly increased resistance to antibiotics (up to 1000-fold higher than in planktonic forms) and to the host immune response. According to the literature, up to 65% of infectious agents are associated with biofilm formation, making them a challenging therapeutic target. This review systematizes current data on the molecular mechanisms of the antibiofilm action of NAC, including disruption of matrix proteins and polysaccharides, degradation of extracellular DNA, suppression of the quorum sensing system, and disturbance of bacterial redox homeostasis. Particular attention is given to synergistic combinations of NAC with antibiotics of five major classes; effective concentrations are provided, and the types of interaction are characterized. The results of clinical studies from the last decade are reviewed, demonstrating the potential of NAC as an adjuvant in urinary tract infections, chronic rhinosinusitis, diabetic osteomyelitis, and cystic fibrosis. The main limitations (pH dependence, instability, low oral bioavailability) are critically evaluated, and approaches to overcoming them using nanoparticles, hydrogels, and combinations with propolis or chitosan are proposed. The review is intended for researchers in antimicrobial chemotherapy and developers of new drug delivery systems.

Introduction. Spray film-forming systems (SFFSs) are dosage forms that form an in situ film when sprayed. One of the key features of SFFSs is partial vapor permeability, a special case of occlusion. Various methods assess vapor permeability by determining the occlusion factor, but disparate approaches in studies prevent harmonizing results and identifying optimal parameters.Aim. Development of a methodology for determining the vapor permeability of spray film-forming systems, measuring the occlusion factor and studying the most significant factors affecting the accuracy of determining this characteristic.Materials and methods. Determination of vapor permeability was carried out using a special setup, consisting of a cell with water and a membrane fixed over it, on which the model composition was applied. Measurement cylinders of 25 ml (Russia) or penicillin vials with a smooth neck of 10 ml (Russia), membranes for filtration and dialysis (nylon, EPM.K, LLC RME "Technofilter", Russia), dialysis bags MEMBRA-CEL® (cellulose acetate, Viskase Companies, Inc., USA) and Sartopure® PP3 (polypropylene, Sartorius Stedim Biotech, Germany) were used. As sealants to isolate airflow around the membrane Parafilm M, C-silicone ZetaPlus L Intro Kit (Zhermack, Poland, Italy), hotmelt adhesive Master Hand (Union Source Со., Ltd., China), UV-curable material "UNIREST" (LLC "StomaDent", Russia) were used. Comparative analysis of materials was carried out on a model composition containing 0.5 % (m/o) Kollicoat® MAE 100P (BASF, Germany), 3 % (m/o) Soluplus® (BASF, Germany), 2 % (m/o) Kollisolv® PEG-400 (BASF, Germany), 70 % ethyl alcohol (SOJSC "Ferein", Belarus).Results and discussion. The combination of Parafilm M and the presented sealants showed high performance. Synthetic membrane occlusion factor for the model substance varied depending on the membrane type from 9.35 ± 3.58 to 16.86 ± 6.09, reflecting low-medium degree of occlusion.Conclusion. In this study optimized techniques for determining the vapor permeability for SFFS were developed. It was observed that rationalized membrane selection, consideration of the probability of moisture absorption by the membranes, method of sealing and cell calibrations, temperature and humidity levels, and vapor pressure were necessary.