3. preparation of a liquid FS-1 drug form;. 4. lyophilization of solution. .... 4. Mark Gibson (2001). Pharmaceutical Preformulation and Formulation: A Practical.
UDC 615.453.62:615.281:615-011-078 STUDY OF SOME PHYSICAL AND TECHNOLOGICAL CHARACTERISTICS OF THE FS-1SUBSTANCE Barinov D.V.1,2, Kalykova A.S.1,2, Sakipova Z.B.1 1
S.D. Asfendiyarov Kazakh National Medical University, Module «Pharmacist-Technologist» 2 Scientific Center for Anti-Infectious Drugs
Some physical and technological characteristics of the FS-1 substance were studied: calculated the porosity by the bulk and true density, pressability and compression ratio, also the lyophilic property and wettability. Key words: FS-1 substance, technological parameters, porosity, bulk density, true density, Hausner ratio, compression ratio, wettability, pressability. Introduction. Value of iodine-containing preparations as antiseptics that all agents of wound infection naturally sensitive to them and the formation of acquired resistance to them is not typical, so iodine is still in the leading position among modern antiseptics. Widely used in medical practice found iodophores - iodine preparations based on non-toxic soluble polymers. They are complexes of iodine with polymers of different structures “Iodinol”- polyvinyl alcohol “Yodopiran”- polyvinylpyrrolidone, “Amiloiodil”- with the starch. The developed FS-1 substance [1] is a complex compound with iodine polidental ligands, which serve associates of carbohydrates and peptides. The active component of FS-1 substance is iodine polymer complex that serves as a matrix capable of retaining a molecule of iodine in the blood included in the preparation, thereby allowing transportation and placement of I2 in the intercellular space. The main stages of the synthesis of substance FS-1 is: 1. preparation of matrix polymer; 2. intercalation of active iodine; 3. preparation of a liquid FS-1 drug form; 4. lyophilization of solution. To obtain the most effective dosage form based on the dry powder substance FS-1 is necessary to study a number of characteristics which have a direct effect on the manufactured form. These characteristics can be classified into major groups: 1. phisical; 2. technological. This article discusses the methodological approaches to the study of some characteristics of FS-1 substance, which is a dry heat labile and hygroscopic dark color powder. On the chemical nature the FS-1 substance is an ionic compound nanostructured complex.
Materials and methods. To investigate the physico-chemical and technological characteristics were synthesized four series of FS-1substance. The synthesis conditions were the same, except the molecular weight of the synthetic polymer matrix. In the production of solid dosage forms of FS-1 substance the important characteristic is the porosity as one of the flowability factors. Powder porosity (P%) was determined from the values of bulk and true density. The bulk density (ρb, kg/m3) were determined by weighing a graduated cylinder with the substance after multiple seals. Hausner ratio was calculated (H), which described the degree of FS-1substance flowability. Determination of true density (ρg, kg/m3) was performed on a Pycnomatic – ATC, Porotec GmbH., Germany. One of the important technological parameters for dry substances is the compaction factor (Kc), which characterizes the time of pressing and pushing force of the formulation during tabletting. Compaction ratio or compression ratio - the ratio of the height of the substance in the press-form prior to compression to the height of the resulting tablets after compression. Compressibility of substance (Kp , g/mm) - the ability of the particles of FS-1 substance for mutual attraction and mechanical interlocking to form a solid tablet model. Since the FS-1 substance includes components differing hygroscopicity, it was determined parameter - hygroscopicity - is the ability of dry substance to absorb moisture from the environment. Degree of hygroscopic substances is generally measured in two conditions: room temperature and 100% humidity. Room humidity should not exceed 80%. The bioavailability of the dosage form influence the ability of the substance to dissolve and its rate of dissolution which, in turn, depends on the hydrophilicity of FS-1 substance. The hydrophilicity is due to the nature and amount of hydrophilic groups on the surface of the particles of FS-1 substance. Hydrophilicity substance studied by determining the degree of wetting in two mechanical states: finely dispersed powder phase and film. Results and discussion. Evaluation of some technological parameters FS-1 substance was carried out on the basis of the study factors affecting the production of mainly solid dosage forms. Among them: porosity, Hausner ratio, bulk density, true density, compression ratio, compressibility, hygroscopicity and wettability. The research results are shown in table 1. Obtained data indicate that as a result of laboratory syntheses were obtained FS1 substance series with varying porosity and particle size, and therefore with different flow properties. Comparison studied physical and technological characteristics are presented as a histogram (fig. 1). FS-1 Substance series No 01130312 is the most optimal for the production of solid dosage forms, when substance has considered ideal flowability characteristics, as evidenced by Hausner ratio (1.09) and good porosity (43.9%).
Table 1 - The results of studies of FS-1 substance Substance batches Parameter Hausner ratio (Н) Porosity (P), % Bulk density (ρ b), kg/m3 True density (ρ g), kg/m3 Compression ratio (Кс) compressibility (Кр ), g/mm
The results of studies of FS-1 substance 01110113 02110113 03170113 04180113 01130312 1.23 1.29 1.26 1.21 1.09 37.2 36.6 38.5 40.0 43.9 1.0513 1.0644 1.0314 0.9798 0.9276 1.6751 1.6783 1.6782 1.6325 1.6537 1.15 1.32 1.44 1.34 1.35 0.183 0.187 0.183 0.191 0.190
FS-1 substance series No 04180113, in its parameter had sufficient technological properties, for use in the manufacture of solid dosage forms. This series has a moderate flowability, porosity and particle size. Other FS-1 substances series (01110113, 02110113 and 03170113), had insufficient flowability due to low porosity and small particle size. The described deficiency will have considerable difficulty in using a substance with such features during the manufacture of solid dosage forms, when dosing. All substances series FS-1 had good compression characteristics and the compression ratio. FS-1 substance has a pronounced hygroscopic in conditions of maximum humidity and mild conditions in the room humidity. After 72 hours study under the maximum humidity FS-1 substance absorbed to go to viscous fluid state, which is unacceptable. Whereas, the hygroscopicity study in room conditions showed that after 100 hours humidity at room upper layer of FS-1 substance contact with medium weak solidified (flowability lost), but at weak hit again acquired flowability. The dependence of the amount of moisture absorbed presented as the kinetic curves in figure 2 for maximum humidity and figure 3 for the room humidity.
Figure 1 - Comparison of the studied physical and technological characteristics of the FS-1 substance
Figure 2 – The dependence of moisture absorbed of FS-1 substance with over time under the maximum air humidity
Figure 3 – The dependence of moisture absorbed substance FS-1 with over of time under room humidity All substances series FS-1 are well wetted irrespective pH, and therefore are hydrophilic . Conclusions: Conducted researches have shown that in the application of FS-1 substance for the manufacture of solid dosage forms must be administered excipients in tablet mass: to improve the flowability of substance FS-1 is advisable to use an emulsifier - magnesium stearate; to improve the disintegration - croscarmellose sodium (Ac-Di-Sol); as a filler, to reduce the hygroscopicity of the FS-1 substance - dextrates or a microcrystalline cellulose.
References: 1. Ilin A.I., Kulmanov M.E. Patent Appl. № 2010/1816.1, Republic of Kazakhstan (30 December 2010). 2. Чуешов В.И.,,Гладух Е.В., Ляпунова О.А., Сайко И.В., Сичкарь А.А., Рубан Е.А., Крутских Т.В. Промышленная технология лекарств. – 2010. Электронный учебник.: http://ztl.nuph.edu.ua/html/medication/index.html 3. Podczeck, Fridun & Brian E. Jones, eds. 2007. Pharmaceutical Capsules. London: Pharmaceutical Press, p. 111. 4. Mark Gibson (2001). Pharmaceutical Preformulation and Formulation: A Practical Guide from Candidate Drug Selection to Commercial Dosage Form. Boca Raton: CRC Press. ISBN 1-57491-120-1. ИЗУЧЕНИЕ НЕКОТОРЫХ ФИЗИЧЕСКИХ И ТЕХНОЛОГИЧЕСКИХ ХАРАКТЕРИСТИК СУБСТАНЦИИ ФС-1 Баринов Д.В.*, Калыкова А.С.*, Сакипова З.Б.**. *Научный центр противоинфекционных препаратов. **Казахский Национальный Медицинский Университет.
Резюме. Изучены некоторые физические и технологические характеристики субстанции ФС-1: рассчитана пористость на основании изученных насыпной плотности и истинной плотности, коэффициент сжатия и прессуемость, а также лиофильность и смачиваемость. Ключевые слова: Субстанция ФС-1, технологические параметры, пористость, насыпная плотность, истинная плотность, коэффициент Хауснера, коэффициент сжатия, смачиваемость, прессуемость.
