СУЧАСНИЙ СТАН СТВОРЕННЯ, ВИРОБНИЦТВА ТА ДОСЛІДЖЕННЯ ТАБЛЕТОВАНИХ ЛІКАРСЬКИХ ПРЕПАРАТІВ Повідомлення 20. Характеристика процесу створення та дослідження гастроретентивних систем доставки лікарських речовин.

Анотація

MODERN STATE OF CREATION, PRODUCTION AND RESEARCH OF DRUGS

M.B. Demchuk, N.P. Darzuli, T.A. Hroshovyi, S.V. Demchuk¹

TernopilStateMedicalUniversityby I.Ya. Horbachevsky

¹JSC “Ternopharm”

Notice 20. The characteristic of process of creating and research of gastroretentive drug delivery system.

Summary: the literature on the benefits of the use and technological aspects of obtaining gastroretentive drug delivery system, such as floating, high density (sinking), mucoadhesive and magnetic systems, super porous hydrogel and matrix systems are summarized.

Keywords: gastroretentive drug delivery system, gastrointestinal tract, intragastric floating systems.

Introduction. Oral administration is the most convenient and preferred means of any drug delivery to the systematic circulation. Dosage forms with a prolonged gastric residence time, i.e. gastro retentive dosage forms (GRDFs), will provide us with new and important therapeutic options. GRDFs extend significantly the period of time over which the drug may be released. Thus, they not only prolong dosing intervals, but also increase patient compliance beyond the level of existing controlled release dosage forms. Gastroretentive drug delivery is an approach to prolong gastric residence time, thereby targeting site-specific drug release in the upper gastrointestinal tract for local or systemic effects. Prolonged gastric retention improves bioavailability, reduces drug waste, and improves solubility for drugs that are less soluble in a high pH environment. It has applications also for local drug delivery to the stomach and proximal small intestine. The most important parameters which has impact on the gastric retention time of oral dosage forms include: density, size and shape of the dosage form, food intake and its nature, caloric content and frequency of intake, posture, gender, age, sex, sleep, body mass index, physical activity and diseased states of the individual (e.g. chronic disease, diabetes etc.) and administration of drugs with impact on gastrointestinal transit time.

Various attempts have been made to retain the dosage form in the stomach as a way of increasing the retention time. These attempts include introducing floating dosage forms (gas-generating systems and swelling or expanding systems), mucoadhesive systems, high-density systems, modified shape systems, gastric- emptying delaying devices and co administration of gastric emptying delaying drugs.

Floating drug delivery systems have a bulk density less than gastric fluids and so remain buoyant in the stomach without affecting gastric emptying rate for a prolonged period of time. While the system is floating on the gastric contents, the drug is released slowly at the desired rate from the system. Floating drug delivery systems can be divided into non effervescent and gasgenerating (effervescent) system.

High density (sinking) or non- floating drug delivery systems have the density that must exceed density of normal stomach content (~ 1.004 gm/cm3). These formulations are prepared by coating drug on a heavy core or mixed with inert materials such as iron powder, barium sulphate, zinc oxide and titanium oxide etc.

Bioadhesive drug delivery systems (BDDS) are used as a delivery device within the lumen to enhance drug absorption in a site specific manner. This approach involves the use of bioadhesive polymers, which can adhere to the epithelial surface in the stomach. Materials commonly used for bioadhesion are polyacrylic acid, chitosan, cholestyramine, sodium alginate, hydroxypropyl methylcellulose, sucralfate, tragacanth, dextrin, polyethylene glycol and polylactic acids etc.

Super porous hydrogel systems. In this approach to improve gastric retention time super porous hydrogels of average pore size >100 micro miter, swell to equilibrium size within a minute due to rapid water uptake by capillary wetting through numerous interconnected open pores.

Magnetic systems. This approach to enhance the gastric retention time is based on the simple principle that the dosage form contains a small internal magnet, and a magnet placed on the abdomen over the position of the stomach.

Conclusions. The basic requirements and approaches to the development of gastroretentive drug delivery systems and examples to obtain tablets that can be kept for a long time in the stomach are considered.

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27. Rezhym dostupu: http://www.prnewswire.com/news-releases/endorex-presents-drug-delivery-and-cancer-product-updates-at-european-conference-74154997.html