Introduction. Due to increase in the frequency of detecting cases of tuberculosis caused by strains of mycobacteria with resistance not only to traditional, but also recently introduced into clinical circulation anti-tuberculosis drugs, it is urgent to search for and develop new drugs that can be effective against multidrug-resistant (MDR-TB) and extensively drug resistant (XDR-TB) strains. One of the most promising classes of such compounds are fluorine derivatives of benzothiazinones, and particularly compound PBTZ169 (INN macozinone). This antibiotic has a high specificity against mycobacteria tuberculosis (M. tuberculosis), inhibiting one of the key enzymes of cell wall synthesis. However, macozinone as an active pharmaceutical ingredient has significant features of physical and chemical properties that hinder the development of oral dosage forms based on it. It is classified as class IV by BCS and is characterized by a very low solubility and lipophilicity, a pronounced dependence of dissolution rate on the pH of the medium, and very low bioavailability when taken orally.Aim. To substantiate the target profile, critical quality attributes and to develop a prototype of an oral dosage form with modified release of macozinone, allowing to maximize its pharmacological activity.Materials and methods. Using pharmaceutical substance macozinone hydrochloride and various excipients, experimental tablets with a dosage of 500 mg macozinone were developed. The influence of the composition of the media and the added excipients on the solubility of macozinone in various biorelevant media, the degree of swelling in the liquid and the degree of mucoadhesion of the experimental tablets to the mucus of the pig stomach were evaluated. The HPLC method was used to evaluate the kinetics of the release of the active substance.Results and discussion. In this work, the expediency of creating macozinone-containing gastro-retentive dosage forms with a slow release of the active substance, the delay mechanism of which is provided by swelling and increased adhesion to the gastric mucosa, has been substantiated. Various tablet samples were experimentally tested in which the modification of the release of the active substance and the degree of swelling and mucoadhesion were varied by introducing various excipients into the formulations, including known swelling and bioadhesive matrix agents.Conclusion. According to the results of the experiments, samples of high-dose (500 mg) swellable and mucoadhesive tablets created by the technology of two-stage granulation with the inclusion of macozinone - hydroxypropyl-beta-cyclodextrin mixtures in the primary granules and introduction of combinations of soluble and insoluble hydrophilic matrix agents into the intergranular space were recognized as the most promising for subsequent pharmacokinetic studies.

Introduction: Cognitive impairment (dementia) is one of the most common pathologies with increasing numbers of patients. Most often they are the symptoms of Alzheimer’s disease and vascular brain diseases, for which such drugs as memantine and citicoline are used. The development of a combination drug with these active pharmaceutical ingredients can significantly increase the effectiveness of therapy. Materials and methods: The pharmacokinetics of memantine and citicoline combination drug was evaluated in comparison with the marketed drugs (reference drugs) of these pharmaceutical substances approved for medical use by determining their content in blood plasma of experimental animals after a single oral administration. Results: Seventy-two hours after the administration of memantine drug, about 5% and 17% of the maximum concentration of memantine released from Akatinol Memantine and the developed combination drug were found in blood plasma, respectively. By the 120th hour after the beginning of the experiment, no memantine was detected in blood plasma of any animal. By the 24th hour after the beginning of the experiment, about 46% and 50% of the maximum concentration of citicoline released from the developed combination drug and the Ceraxon drug were found in blood plasma of the rabbits, respectively. Discussion: It was detected that the amounts of released memantine and citicoline from the developed combination drug exceeded the amounts of the appropriate pharmaceutical substances released from the reference drugs. The bioavailability of these substances from the developed combination drug was higher than from the marketed mono formulations used as reference drugs. Conclusion: Based on the obtained results of memantine and citicolineconcentrations in bioassays, the main pharmacokinetic parameters of the studied preparations were calculated, the results of which showed the superiority of the developed combination drug over the reference drugs.

Background: Conventional ophthalmic eye drops have low bioavailability (<5%) and poor patient adherence, driving the development of sustained-release ophthalmic drug delivery systems. The lacrimal drainage system represents a unique anatomical site for minimally invasive depot formulations. Objective: To summarize and critically appraise punctal and intracanalicular drug delivery systems, occlusive devices, and in situ-forming hydrogels with respect to composition, release mechanisms, clinical efficacy, safety, and critical quality attributes (CQAs). Methods: A narrative literature review was conducted using PubMed, Scopus, Web of Science, Google Scholar, ClinicalTrials.gov, and patent/regulatory sources, including FDA materials and Google Patents, covering 2001–2026. Anatomical features, materials, active pharmaceutical ingredients, release profiles, and adverse events were analyzed. Results: Seventy-one sources were included. Occlusive plugs without an active pharmaceutical ingredient demonstrate premature expulsion in up to 57.4% of cases and bacterial colonization in 44%. Drug delivery systems provide release from 7 days (PEGDA hydrogels) to 3 months (Eximore, Ocular Therapeutix™). DEXTENZA^® (dexamethasone) is FDA-approved for postoperative inflammation, whereas pivotal trials of travoprost (OTX-TP) and latanoprost systems (L-PPDS, EXP-LP) did not demonstrate superiority over placebo or eye drops. In situ systems eliminate size-fitting requirements but face challenges related to gelation control and biodegradation. Conclusions: We propose the following candidate CQAs: retention (>80% over 4 weeks), swelling degree (30–60%), controlled burst release (<40% within 24 h), and mechanical compatibility. The proposed QTPP matrices for punctal, intracanalicular, and in situ systems may guide the development of ophthalmic drug delivery platforms.

The pharmaceutical development of a fixed dose combination form of citicoline and memantine for the treatment of cognitive disorders, which will improve compliance is a topical area of research. Purpose: to investigate the technological properties of the active pharmaceutical ingredients: memantine hydrochloride and citicoline monosodium salt in the framework of the development of a fixed dose combination modified release. The samples of pharmaceutical substances citicoline "Kyowa Hakko Bio Co., Ltd." (Japan) and memantine hydrochloride - Hetero Drags Limited (India) were used. Technological studies of the substances were carried out in accordance with the requirements of the State Pharmacopoeia of the RF XIV edition. It was revealed that the particles of the investigated substances show an anisodiametric shape, the anisodiametric shape of the analyzed particles indicates possible poor flowability of APIs, which predicts difficulties in dosing during the tablet compression process. The following characteristics were studied: the ability of the powder to compaction, the bulk density and compressibility index, Hausner ratio were established. It was found that, according to the USP classification, the flowability of substances can be characterized as very, very poor. Pharmaceutical substances of memantine hydrochloride and citicoline monosodium salt have unsatisfactory technological properties, which can complicate the processes of die filling and dosing of pharmaceutical substances during tableting tablet compression. To prevent these disadvantages, it is further recommended to provide research on the possibility of using wet granulation, or the usage in the composition of the tablet mass of excipients with a high bulk density and good flowability. Thus, within the framework of pharmaceutical development, the physicochemical properties of the pharmaceutical substances memantine hydrochloride and citicoline monosodium salt were investigated.

The development and study of the fixed dose combination tablets of citicoline and memantine is the relevant problem. The purpose of this study was the assessment of acute toxicity and local irritating effect of the new combined drug, the modified release tablets (citicoline 500 mg + memantine 10 mg). Material of research: fixed dose combination of modified release tablets (citicoline 500 mg + memantine 10 mg) (NovaMedica Innotech, Russia). The tested drug was administered intragastrically to males and females of half-plant outbred rats at a dose of 2000 mg/kg in the amount of active substances. According the research results, the death of animals was not noted. As it was found the value of LD50 for the test drug in the intragastric administration is>5000 mg/kg in accordance with OECD Test No.423. The tested drug can be attributed to the 5th grade of toxicity on the international classification of GHS, because LD50> 5000 mg/kg (V/g) and to 4 class of low-toxic compounds as per Hodge and Sterner classification: 500