CURRENT ASSORTMENT OF GASTRO-SOLUBLE POLYMERS USED IN PILL COATING AND FILM APPLICATION METHODS

CURRENT ASSORTMENT OF GASTRO-SOLUBLE POLYMERS USED IN PILL COATING AND FILM APPLICATION METHODS

Ciobanu Nicolae

Dr. pharm., Associate prof., Department of Drug Technology, “Nicolae Testemitanu” State University of Medicine and Pharmacy,

Chisinau, Republic of Moldova

Guranda Diana

Dr. pharm., Associate prof., Department of Drug Technology, “Nicolae Testemitanu” State University of Medicine and Pharmacy,

Chisinau, Republic of Moldova

Ciobanu Cristina

Dr. pharm., Associate prof., Department of Drug Technology, “Nicolae Testemitanu” State University of Medicine and Pharmacy,

Chisinau, Republic of Moldova

Petrache Ana

Undergraduate of the Faculty of Pharmacy, “Nicolae Testemitanu” State University of Medicine and Pharmacy,

Chisinau, Republic of Moldova

ABSTRACT

Currently, tablets are the most common pharmaceutical form, occupying about 40% of the total production of drugs on pharmaceutical market in the Republic of Moldova. Gastro-soluble tablets present medicinal preparations that have seen a spectacular evolution over time, due to technical and scientific progress. The purpose of film-coated tablets is to mask the unpleasant taste, thus obtaining a better tolerance, to increase bioavailability of the active substance and for achievement of a faster effect. Of the large group of polymers used for tablet coating, hypromellose and methacrylic acid esters containing amino or thiol groups are widely used. It should be noted that the most popular are swelling hydrophilic polymers, soluble in various parts of the gastrointestinal tract. This is due to the fact that it is much easier to control the kinetics of the release when using such polymers, and also to the fact that polymers of this type are biodegradable. Thanks to a wide range of polymers, it becomes possible to program the rate, degree and place of substances release in the body, during the development of dosage forms. In pharmaceutical practice, methods such as: cover in pan, in fluidized bed, in installations with centripetal action and by compression are used to coat tablets with stomach-soluble films. Currently, tablets are an industrial pharmaceutical form, the development of which is closely related to technological and scientific advances in medicine and pharmacy.

АННОТАЦИЯ

В настоящее время таблетки являются наиболее распространенной фармацевтической формой, занимая около 40% от общего объема производства лекарств на фармацевтическом рынке республики Молдова. Таблетки, растворимые в желудочно-кишечном тракте (ЖКТ), представляют собой лекарственные препараты, претерпевшие впечатляющую эволюцию с течением времени благодаря техническому и научному прогрессу. Покрытие таблеток пленочной оболочкой, позволяет защитить от неприятного вкуса и запаха, улучшает внешний вид, упрощает глотание таблетки, придает ей характерный внешний вид и служит защитным барьером. Из большой группы полимеров, для покрытия таблеток, широко используется гипромеллоза и сложные эфиры метакриловой кислоты, содержащие аминогруппы. Следует отметить, что наибольшей популярностью пользуются гидрофильные набухающие полимеры,  растворимые в различных отделах ЖКТ. Это связано с тем, что регулировать кинетику высвобождения при использовании таких полимеров значительно проще, а также с тем, что полимеры данного типа являются биодеградируемыми. Благодаря широкому выбору полимеров становится возможным программировать скорость, степень и место высвобождения веществ в организме при разработке лекарственных форм. В фармацевтической практике для покрытия таблеток с растворимой в желудке пленкой используются такие методы, как: нанесение покрытия путем распыления раствора в дражировочном котле, нанесение покрытия в установках с центростремительным действием, нанесение покрытия путем прессования. В настоящее время таблетки представляют собой промышленную фармацевтическую форму, разработка которой тесно связана с технологическими и научными достижениями в области медицины и фармации.

Keywords: tablets, polymers, gastrointestinal tract, pharmacy.

Ключевые слова: таблетки, полимеры, желудочно-кишечный тракт, фармация.

The polymer film coating process is a relatively recent discovery, compared to sugar coating and it emerged from the need to improve some of the disadvantages of dragees. The oldest reference to the film coating process date from 1930, but the first available filmed tablets were produced by Abbott Laboratories in 1954. In the early 1950’s, Dr. Dale Wurster, professor at the University of Wisconsin, patented the filming method by the air suspension technique, and in the next 12-15 years several hundred scientific develoments on this subject were published [2].

In the European Pharmacopeia coated tablets are included in the general tablet monograph (Compressi. Tabulettae) along with the uncovered ones, however, the two categories of tablets are defined: dragees, coated pills or tablets [3].

From the point of view of coated tablets classification according to the place of release of the medicinal substance, we distinguish:

• Gastric-soluble film coated tablets. Their manufacture includes films that protect the moisture tablets, in the same time it disintegrates during 10-30 minutes in the stomach.
• Enteric-coated tablets. Their manufacture includes coating films that locate the active principle eliberation in the intestines, prolonging their action. By using different polymers and adjusting the thickness of the film it is possible to disintegrate the tablets in a certain sector of the intestinal tract [7].

The assortment of macromolecular substances used for non-enteric coating (gastro-soluble films) includes:

• Cellulose derivatives: methylcellulose, ethylcellulose, hydroxypropyl cellulose (Sepifilm^®), microcrystalline cellulose (Avicel^®).
• Polyvinyl combinations: polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl chloride.
• Substituted polysterols.
• Polyacrylates (Eudragit^®).

Tablet film coating is a technology-driven process, and the evolution of coated dosage forms depends on advancements in coating technology, equipment, analytical techniques, and coating materials [6].

The purpose of the work consists in the evaluation and description of the current assortment of gastro-soluble polymers used in the coating of tablets, methods of formulation of polymers in non-enteric coating material and brief description of the techniques for applying gastrosoluble films in the manufacturing process of coated tablets.

Materials and methods used for the study included the analysis of bibliographic information and reviews, published in various national and international journals and books of pharmacy and pharmaceutical technology.

In the production of coated dosage forms, the composition of coating material depends on destination of the product (tablets for swallowing, sucking tablets or chewing tablets), the time during which the active substance must be released (with immediate release, with delayed release or with controlled release) and the place where the active substance must be released (in the oral cavity, in to the stomach or intestine). The coating process is generally determined by the composition and nature of the material that forms the coating.

Depending on the purpose, there are two main types of tablet coating, which differs in formulation and sometimes in applied technology:

• Coating with gastro-soluble films.
• Coating with shells that modify the release of the active substance from pills.

Coating with gastro-soluble films is intended for:

• Masking the taste, the smell and the colour of the active substance;
• Protect the active substance from light, air and moisture;
• Avoidance of incompatibilities between components;
• Increasing the mechanical strength of tablets;
• Improving the appearance and ensuring the identification of the coated medication;
• Facilitate swallowing of tablets.

Water-soluble or acidic substances are used for coating, forming layered coatings or coating films. They belong to the category of non-film-forming materials: sugar, sugars and polyols. Gastro-soluble film-forming polymers are: hydroxypropylmethyl cellulose, methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, sodium carboxy-methyl cellulose, polyvinylpyrrolidone, polyethylene glycols, salts of entero-soluble polymers or methacrylic esters containing amino groups (diethyl-aminomethyl cellulose, benzyl-amino cellulose, Eudragit E100) [6].

The film coating is used for coating with solutions or dispersions of the nominated polymers and is a modern alternative to sugar coating. Initially polymer solutions in organic solvents were used, nowadays being replaced by solutions or suspensions in water.

Thus the coating films consist of film-forming polymers which are applied to the tablet cores in the form of solutions or dispersions and other dissolved or suspended excipients. After removal of the solvent or dispersion vehicle, the polymers and the other excipients remain on the core in the form of a continuous and uniform film. The other excipients can sometimes make up even more than 60% of the coating, depending on the coating capacity of the polymer. Along with the film-forming polymer, are required: plasticizers, dyes, sliders, lubricants, dispersants, solvents or vehicles, etc.

The polymers must be slightly soluble in the used solvent to allow flexibility in formulation, to have a good coverage capacity and must be soluble in gastrointestinal fluid, in order not to compromise the bioavailability of the active ingredient. The molecular weight of the polymers is of great importance and must be taken into account in the selection of the coating process [2].

The film coating process of the tablets has taken a great development, due to the shortening of the stages, which are quite numerous. The technological flow of manufacturing film-coated tablets is shown in figure 1.

Figure 1. The technological flow of manufacturing of film-coated tablets

In the case of film-coated tablets, the core is coated with a polymer film or film, relatively thin, which represents 1-10% of the weight of the entire tablet. In this way the nucleus retains its initial organoleptic characteristics, and the whole wrapping operation is much shorter.

The technological process of applying of gastro-soluble coating material several methods are used such as: cover in pan, in fluidized bed, in installations with centripetal action and by compression coating [1,5].

However, most of the time the spray film solution is applied. Spraying the coating film allows very fine atomization of the drops, which are thereby deposited on the moving cores, ensuring a uniform coverage, furthermore the drying is done quite quickly (figure 2).

Figure 2. The representation of the process of spraying coating film [4]

Compression coating consists of a two-stage coating process: core compression, and then compressing the dry coating mixture around the core. Sometimes, separate compression of the core is not necessary. In this technique the application of the coating on the core is done dry by compression, without the involvement of humidity and heat. The tablets obtained by dry coating are also called mantle tablets. But the application of these coatings requires special compressing machines (double-sided rotary machines).

In conclusions film coatings, especially gastro-soluble films, are the most promising today. Coating with thin films compared to classic filming has a number of advantages. It greatly shortens the coating time and reduces the consumption of the coating material, so they are more economically reliable. The insignificant increase of the mass and volume of the tablets has an advantage in administration and reduces the cost price of the packaging. The film-coated tablets retain their original shape, even the original engravings can be maintained, which reduces the chances of error in delivering.

References:

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3. European Pharmacopoeia, 5th ed., EDQM, European Pharmacopoeia, Council of Europe, B.P. 907, F - 67029 , Strasbourg, France , July 2004 .
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