РАЗРАБОТКА РЕЦЕПТУРЫ И ТЕХНОЛОГИИ ПЕНООБРАЗОВАТЕЛЯ ИЗ МАСТИЧНОЙ (PISTACIA LENTISCUS L.) КАМЕДИ.

An acid fraction derived from the evergreen plant of Mastic gum(Pistacia lentiscus L., family Anacardiacae, genus Pistacis L.) has been found to have bactericidal activity against 11 strains of Helicobacter pylori. However its healing potential is significantly reduced by poor solubility and low biological penetration. Therefore, the current problem is to develop a system that provides increased penetration of the drug into the stomach through the epithelial barrier. Foams are especially interesting in this regard. Foams are light systems, they do not swell, on the contrary, they grow in volume, completely covering the mucous membrane. The foams do not require taste correction and are designed to deliver a therapeutic substance from the skin and mucous membranes and provide an effective treatment. The aim of the research was the determination of formulation and development of technology of innovative medicinal form from Mastic gum. Based on biopharmaceutical studies, the formulation of capsules containing a foaming powder composition was determined: Mastic gum 250.0; Sodium lauryl sulfate (SLS) - 9.0; Lecithin - 12.6; Xanthan 4.5; Gelatin 4.5; Isomalt 90.0; Dry egg whites - 41.0; Sodium bicarbonate - 21.0; Citric acid - 6.0; Metocell M102 - 10.0; Talc - 1,4. The technology of preparation of Mastic gum foaming powder containing capsules has been developed.Foaming capsules containing Mastic gum, in artificial gastric juice, with foam-forming ability and foam stability meet the standard requirements for foam systems.

MEDICATIONS FOR ERADICATION OF HELICOBACTER PYLORI (REVIEW).

Helicobacter pylori is a pathogenic microorganism that causes gastritis, duodenitis, peptic ulcer disease of the stomach and duodenum. Recent data confirm the close association of Helicobacter pylori with the development of gastric cancer. Due to the failure of standard H. pylori eradication regimens, intensive studies are being conducted to develop targeted local delivery and prolonging activity drug forms. Based on scientific studies, sufficient knowledge has been accumulated on the inhibitory action of biologically active substances of plant origin: peptides, polyphenols, terpenes, fatty acids on Helicobacter pylori, which allows developing an alternative treatment scheme. It is especially important today to create local and long-acting, high-density, mucoadhesive, floating and swelling systems. Unlike other forms of medicine, foam systems are interesting in this respect. They are distinguished by a large touch surface, high bioavailability and rapid therapeutic effect. Foam provides economical dosing, better contact with the mucous membrane, and give the drug a prolonged action. Under the influence of body temperature the foam increases in volume, filling all free spaces and channels. However, the foam can provide high concentrations of the medicinal substance for up to 4 hours.

FORMULATION THERMORESPONSIVE NANOCOMPOSITE HYDROGELWITH EMBEDDED PLGA NANOPARTICLES CONTAINING CYTOTOXIC AGENT.

The aim of the study was to develop and characterize the nanocomposite in-situ hydrogel as local drug delivery system of cytotoxic agent. In-situ hydrogel consisting of 15% thermosensitive (Poloxamer 407) and 1% mucoadhesive (sodium alginate) polymers was selected as the optimal formulation by the conducted studies. The influence of nanoparticle concentration on gelation time and temperature has been experimentally established. As a result, the optimum concentration of nanoparticles (5%) is selected, which does not alter the gel forming process. The resulting nanocomposite hydrogel was characterized through Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), rotational viscometer (LVDV-1T). FT-IR spectra confirmed the PLGA nanoparticles presence within the hydrogel matrix through the absorption peak located at 1750 cm-1. SEM images allowed observing the nanoparticles to be homogenously dispersed. The release pattern of the active substance from the nanocomposite hydrogel is following: at 72 h, 64% and 78% of the active substance were released into the phosphate buffer and cell culture area, respectively. Irritation test on hen's egg model revealed that formulated nanocomposite hydrogel did not show damage of vascular system.

BIOPHARMACEUTICAL UNDERSTANDING OF FORMULATION PREPARATION VARIABILITY OF PLGA NANOPARTICLES LOADED WITH ERYSIMUM EXTRACT.

The purpose of this study was to evaluate effect of process and formulation variables on the preparation of Erysimum extract loaded PLGA nanoparticles. The influence of the various biopharmaceutical factors such as type of organic solvent, type and concentration of surfactant, polymer concentration in the organic phase, ratio of organic phase and water phase were studied. Modified emulsification solvent evaporation method was used for preparation of nanoparticles. Based on the performed experiments optimal formulation of nanocomposite is suggested. Nanoparticle size, size distribution and entrapment efficiency were determined. Among five non-ionic surfactants polyvinyl alcohol provided more stable nanocomposite. Influence mechanisms of different surfactants on nanoparticle formation are provided. Water miscible organic solvent, acetone obtained 232 nm nanoparticles with improved size distribution. Entrapment efficiency was increased to 73% by reducing ratio of organic and water phases. Based on experiments nanoparticles with stable, reproducible properties are fabricated.

FORMULATION AND TECHNOLOGY DEVELOPMENT OF HERBAL PHENOLIC BIOPOLYMER-CONTAINING FILMS FOR BURN TREATMENT.

Application of phytofilms based on biosolublepolymers is considered as a prospectivemethod for burn treatment . Herbal remedies contain biologically active substances, that are relatively less toxic, do not cause skin irritation or allergic reactions and, importantly, affectstrains of the microorganisms and viruses resistant to antibiotics and synthetic drugs. Nowadays, the advantages are given to such burn healing drugs, which along with high specific efficacy, have analgesic, anti-inflammatory and antimicrobial effects, and don't irritate the tissues. The mentioned peculiarities are characteristic for a new herbal phenolic biopolymer poly[3-(3,4-dihydroxyphenyl) glyceric acid](PDGA), isolated from the roots and stems of different comfrey species . The aim of the study was the development of the formulation and technology of biosoluble films for burn treatment on the basis of PDGA. The optimal content of phytofilm for burn healing was selected on the basis of the biopharmaceutical study results. The impact of the film-former on the quality, adhesion and moisture absorption of the phytofilmhas been studied. The optimal degree of the phytofilm moisture, determining its high adhesive properties,was established. The film prepared on the basis of sodium alginate, with 30.4% humidity, demonstrated the greatest adhesion strength. After investigation of the PDGA release it was found, that the hydrophilic bases such as: sodium carboxymethyl-cellulose (69.2%) andsodium alginate (78,65%) appeared to be optimal among the others. At the same time, taking into consideration the disadvantages of sodium carboxymethyl-cellulose (tautening effect on burnt surface, relatively low stability), a film based on sodium alginate has been chosen. The manufacturing technology for obtaining PDGA-containing phytofilm by casting is proposed. Theshelf-lifeofproposedPDGA-containingphytofilmis 2 years.

DEVELOPMENT OF FORMULATION AND TECHNOLOGY FOR THE POLY[3-(3,4-DIHYDROXYPHENYL)GLYCERIC ACID] GEL.

One of the most actual problems of pharmacy is the development of medication forms for external application with complex effects on (gel, emplastro, aerosol, etc.) skin wounds, burns and inflammatory factors. The centuries-old practice of using phyto-preparations (herbal remedies) proved that they have fewer side effects in comparison with synthetic drugs. Despite the wide application of herbal preparations, in the literature there is a little information about their application in development of wound and burn healing modern dosage forms. Among the medicinal plants with the mentioned pharmacological actions, comfrey (Symphytum L.) should be distinguished. Phenolic polymer poly[3-(3,4-dihydroxyphenyl)glyceric acid] (PDGA) or poly[oxy-1-carboxy-2-(3,4-dihydroxyphenyl)ethylene], amounting approximately 25% of polysaccharides and 1.5-2.5% of dry plant material, were isolated from the roots and stems of Caucasian comfrey species (S. asperum, S. caucasicum). Contrary to polysaccharides this phenolic polymer of Comfrey appeared to have a high immunomodulatory (anticomplement), antioxidative, antilipoperoxidantive, anti-inflammatory and wound-healing efficacy/activities. The aim of the study was development of the composition and technology of PDGA-containing gel. According to the results of complex biopharmaceutical studies PDGA gel optimal composition has been proved. The technological scheme for preparation of PDGA gel has been developed. PDGA gel stability under normal conditions of storage at +40С was studied. The gel has a shelf life (determined expiration date) of 2 year.

[Perilla nankinensis Decne by using melt granulation method].

The aim of the research was to work out the technology and tablet composition from the overground parts of the Perilla nankinensis Decne on the base of complex research. The dry extract was prepared from dried overground parts of perilla introduced in Georgia. The structural-mechanical and technological character of tablets and their masses were identified by the known methodic. Friability was studied by defining the fluctuation and bending corner. Volume density was established by using vibration cylinder. Volume density of powders was studied by pyknometers. Porosity was calculated by the bearing of volume density of the masses. The size of pressing was established by defining the firmness of tablets. The granule composition was defined by analysis. Disintegration and dissolution were studied by using "rotating basket" and "basket-rack assembly". From the result we got it was clear that the dry extract for research don't have good fluctuation and pressing. It should be mentioned that it contained moisture and is hygroscopic. As the character of substances is not satisfied it was necessary to select new assisting substances and studying and using additional technological method. We have selected some more additional substances for optimal firmness and for the purpose of shortening the time of tablet dissolution. There were also selected parameters of optimal pressing force. Assisting substances are practically selected and theoretically accepted on the base of studying technological and physical-chemical character features of the substances of the dry extract from the over ground parts of Perilla nankinensis Decne. As a result optimal composition of tablets is delivered. It is also scientifically proved and practically offered optimal technological parameters of tablets forming melt granulation method.

[Development of inhalation powder formulation of gentamicin sulphate].

Aminoglycosides, including gentamicin, are considered among the most useful classes of antibiotics for treating Pseudomonas aeruginosa infections. The major drawback of aminoglycosides is the need for their relatively high-dose intravenous administration, which carries the potential for systemic toxicity. Granulometry analysis of gentamicin sulfate powder (substance) has shown, that generally it consists of large particles, and thus is not suitable for inhalation. Six different inhalation composition containing gentamicin sulfate has been developed, one of which showed the best inhalation properties. Technological chart and pilot Master formula for inhalation gentamicin sulfate composition delivered via Handi Haler have been developed.

[Nebulized drugs: the evolution?]. / Nébulisations médicamenteuses : évolution ?

The revival of nebulization as a drug delivery route is real. The current delivery systems respond to the new European norms, the new mesh-vibrating nebulizers allow delivering drugs more quickly, other nebulizers, more performant because of less drug losses and of a better lung deposition of the drug, are in progress. Only 12 drugs are commercialized for nebulization. All are available in dispensaries, some requiring a first prescription by a physician working in a hospital (cystic fibrosis drugs), others requiring a prescription from only some specialists as paediatricians or pulmonologists (bronchodilators). Works are in progress concerning the diameter and shape of the drug particles (nanotechnology) and also concerning the use of nebulized drugs for a systemic effect (vaccines, insulin, cyclosporine, anticancerous agents, etc.).