COVERING THE TABLETS WITH ENTERIC COATING BASED ON WATER SOLUTIONS OF POLYACRYLATES

27 Sep 2013

УДК: 605.483.64

Ye.V. Flisyuk, Ye.N. Kirillova, Z.B. Sakipova, S.K. Zheterova, A. Kadyrbai

St. Petersburg State Chemical-Pharmaceutical Academy
Kazakh National Medical University named after .S.D.Asfendiyarov

 

Nowadays it is impossible to imagine   preventive treatment and therapy of most diseases without solid dosage form, tableted pharmaceutical substances in particular. Their technology is continuously being developed and improved. Thanks to introducing special components (auxiliary substances) and using definite technological methods traditionally oral, solved mainly in  guster tablets now can be enteric with  quick action or vice versa  durable action, being solved in prescribed  part of  gastrointestinal tract. To provide those properties there are widely used film coats applied to the tablets core surface.

In our country and abroad researchers are looking for new auxiliary substances, developing new compositions of film coat for tablets with the aim of their assortment widening and quality improving. Leading firms-manufacturers of  auxiliary substances  for coating are «Colorcon» (USA), «BASF» (Germany), «Warner Jenkinson Europe» (USA), «Evonik industries» (Germany), «ShinEtsu» (Japan),   Aqualon KLUCEL® (Germany) and others. They manufacture both essences and ready made compositions of film coat for tablets. However dependent on pharmacological action, tablets technological properties there occurs the necessity of film forming composition amendment,  introducing into it various auxiliary substances (plasticizers, emulgents, pigments, etc.).  It  can influence in its turn the profile of active substances  release from tablets.

In the scope of manufacturing coated tablets an acute problem is creating the coating having selective solubility in the environment with different рН value, providing reliable protection of pharmaceutical substance from impact of moisture, air oxygen, gastric juice damaging affect. [1].

Enteric coat facilitates pharmaceutical substance localization in concentrated form directly in the appropriate  intestinal tract part, excludes side effect of some pharmaceutical substances on mucous coat of stomach and resolves dyspepsia, prevents  degrading of most antibiotics, ferments, hormones, some vitamins due to stomach acidic environment influence [2].

Most widely used enteric coats are acetyl phthalyl cellulose [3], phthalate and shellac [4]. But the coats require using organic and toxicant solvents. So lately there the problem of using enteric coats made from water polymers dispersion has become urgent as it secures standard sanitary-hygienic labor conditions and prevents fire and explosion hazard situation at production facilities.

Many foreign firms offer for this aim synthetic polymers based on polyacrylate.

This paper presents work on a comparative study of three film-forming compositions under various brand names (Kollicoat MAE 30DP, Kollicoat MAE 100P and ACRYL-EZE), which contain a copolymer of methacrylic acid and ethyl acrylate as a film former.

The firm BASF manufactures methyl-acrylic acid copolymer and ethyl acrylate to produce coats resistant to  gastric juice affect under the Kollicoat trade mark [5]. Kollicoat MAE are slightly acidic polymers solved at рН 5,5. The various trademarks differ from one another in the aggregate state. Among them the most widely used ones are: Kollicoat MAE 30DP and Kollicoat  MAE 100P. Kollicoat MAE 30DP is water dispersion of milky color with solid substance content of 30%.

Kollicoat МАЕ100P is white, easily dispersible powder produced from МАЕ 30DP by means of spray drying. Having neutralized carboxy groups in powder permits its easy dispersing in water without use of auxiliary substances, for instance not adding NаОН. It is recommended to add 1, 2- propylene glycol as a plasticizer to film forming solution.

Kollicoat МАЕ100P as compared to  Kollicoat МАЕ 30DP has following advantages:

— longer powder shelf-life;

— powder transportation ease.

Kollicoat МАЕ meets pharmacopeia requirements of the USA, Europe and Japan.  Kollicoat contains 0, 7% of laurilsulfate and 2, 3% of tween-80 as emulgents.

These formulae for coats require plastifier adding to make the film elastic.  Recommended plastifier is   1, 2- propylene glycol with concentration of 10% – 25% of the dry polymer weight.

Currently the firms manufacturing compositions for coats are in the process of perfecting their composition to improve the coats technological characteristics and making their preparation easier.  Therefore they add plastifier, emulgents, pigments, titanium dioxide, talk (it fulfills substances separation function upon coating) directly to the initial composition.

One of those products is the composition of an American firm Сolorcon under the trademark ACRYL-EZE [6].  Unlike Kollicoat ACRYL-EZE contains TiO2 and talk. Talk performs substances separation function, lowers stickiness degree of the drying lacquer film and promotes making a smooth composition surface. TiO2 gives the coat even white color, thus making the lacquer film opaque. One more distinction of ACRYL-EZE is the fact that it already contains plastifier in its composition (triethylcitrate).

Plасево tablets made of lactose have been used as core tablets.

In order to study coat formula properties surface strain (s) has been investigated and polymers solution viscosity has been evaluated.

Table  1  presents formulae characteristics for  coats.

Surface strain (s) study has been carried out for  evaluating interrelation with tablets surface  wetting ability as tablets coat quality is affected by adhesive force (film adhesive power with a tablet surface), also  by cohesive force (interaction between the molecules in the polymer itself). With surface strain (s)  decreasing  the surface wetting ability is improved and consequently the film adhesion to the tablet surface increases which makes the coat gain in stronger.

Experiments outcomes prove that surface strain (s) (Acryl-eze) has somewhat lower value due to adding to it big amounts of emulgents (sodium lauril sulfate) which represents surface active substance.

Polymers solutions viscosity assessment showed that pigment and talk adding  increases to a certain extent the dispersion viscosity as it is in case with Acryl-eze. Kollicoat MAE 100P viscosity is by an order higher than  Kollicoat MAE 30DP viscosity and it gradually decreases  in exponential law due to  air bubbles being forced out from dispersion and stress relieve between latex particles.

Table 2 gives results of received model film characteristics research which show that all the films meet the requirements for solubility (0,1 М НСl  is not solved within an hour; 1,5% NaHCO3  solved less than within an hour) which is an indispensable quality index for enteric coats [7]. As well there are given the values of films steaming velocity and elasticity comparison per point-based system.

The value of films steaming ability is of great significance for tablets coating process as upon non-conformity of coating steaming capacity to the volume of steam formed during drying the core there might take place coating integrity disorder. In the process of coating it is desirable for the film to have vapor permeability as high as possible, but on the other hand when being stored high film vapor permeability will affect the tablets shelf life as moisture will actively penetrate into the core.

Figures 1 and 2 show dependence of  film vapor permeability and steaming velocity on plastifier content.  Test results show that plastifier content growing leads to steaming ability value increase (the highest steaming ability have the films with  20% plastifier content, the least- with  10% plastifier content). Films manufactured of Kollicoat MAE 30DP and Kollicoat MAE 100P have similar steaming values. Films manufactured from Acryl-eze are almost twice slower moisture permeable which is connected with talk and TiO2 addition into its composition. They fill in the pores in the film and prevent moisture permeability. Film coating has been conducted in a laboratory apparatus of boiling layer “Aeromatic” .

Initial tablets mass in experiments was 0,2 kg, coating solution consumption- 0,008 – 0,080 ml/sec, air temperature at product reservoir input — 60оС.

In the process of coating 7% of coat (Kollicoat MAE 30DP and Kollicoat MAE 100P) and 8% of Acryl-eze have been used. After coating solution supply termination there was fulfilled the process of drying tablets with coating during 3–5 minutes at fluidizing air consumption of 110 -150 m3/hour.

To study the uniformity of tablets coating in the process of covering tablets with  film coating of ethyl acrylate and methyl-acrylic acid copolymers methodology elaborated at TPhS S-P chemical-pharmaceutical academy  chair has been used. [8].

On the base of the outcomes of weight analysis of specimens selected from the layer there has been fulfilled calculation of distribution curves. Standard differential distribution curves of tablets per coating mass on them are given on Fig.3. Analysis of received results showed that tablets distribution dispersion per coating mass on them  received with use of  Kollicoat MAE 30DP (15%, 20%)  and Kollicoat MAE 100P (20%) is lower than upon using Kollicoat MAE 30DP (25%) and Acryl-eze (20%). Thus, using Кollicoat (in concentration up to 20%) gives more even coat per tablet mass.

Evaluation of penetrance of coated tablets in 0,1 М of НСl solution has been done and correlation of received values with steaming ability values of some films has been revealed.

Assessment of coated tablets pressure resistance regarding core-tablets showed that pigments addition into the coats  sufficiently increases tablets strength  unlike the coats received from dispersions without pigments.

Within the conducted researches properties of three film forming formulae  based on  methyl-acrylic acid and  ethyl acrylate copolymer have been studied; optimal polymer concentration (20%) and plastifier (10%), referring Кollicoat has been selected; model films characteristics and  quality indices of  coated tablets have been investigated. Consequently it can be concluded that for producing  enteric coat meeting pharmacopeia requirements there can be successfully used  Kollicoat МАЕ30DР and Acryl-eze compositions

Kollicoat МАЕ30DР advantage as compared to Acryl-eze is as follows:  the first one has the best technological characteristics (low viscosity, absence of additives creating complication upon spraying) and provides more homogeneous coating as compared to Acryl-eze.

references

1       А.с. 1091930 USSR, МКИ В 05.С.9/04. Coating the solid pharmaceutical forms/  Minina S.A.,  Yefimova L.S.,  Bagdasaryan A.A. (the USSR).-#3374533/28-13; Presented  23.11.81; Published. 15.05.84. Bulletin # 18.-15p.

2       Bertovska Zh.E.,  Akifjyev O.N.,  Krolle S.V.  Film coating of   valtaren, etacine tablets, ИОС-1734//Basic guidelines of  pharmacy development: Brief outlines of reports. II pharmacists congress. Latvian SSR.-Riga, (1984), p.p.179-180.

3       Kryazhev V.N., Pogosov Yu.L.  Properties of acetyl phthalyl cellulose // Chemical-pharmaceutical journal. #5, 43-45 (1973)

4       Yefimova L.S.,  Abstract of a thesis of the candidate of pharmaceutical sciences. Leningrad (1971)

5       Kollicoatâ MAE. Methyl-acrylic acid and ethyl acrylate copolymers for producing coats resistant to  gastric juice affect// Technical information.

6       ACRYL-EZE // Technical information.

7       State pharmacopeia of the USSR. XI edition. Issue 2. Moscow. «Meditsina»,

 
 

Таблеткаларды полиакрилаттың сулы ерітіндісі негізіндегі  ішекте ертитін қабықпен қаптау

Түйін: Осы мақалада пленка түзуші заты метакрил қышқылының акрил қышқылы этил эфирінің сополимері болып табылатын әртүрлі саудалық атаумен (Kollicoat MAE 30DP, Kollicoat MAE 100P и ACRYL-EZE) берілген үш түрлі пленка түзуші құрамның салыстырмалы зерттеулері берілген. Жүргізілген зерттеулер нәтижесінде таблеткалардың сапа көрсеткіштері модельді  пленкалар құрамына тәуелділігі анықталды:  полимердің оптимальды концентрациясы  20%  және пластификатор — 10%. Kollicoat МАЕ30DР и Acryl-eze құрамындағы пленка түзуші қабықтармен қапталған таблеткалар сапасы Фармакопеядағы ішекте еритін таблеткаларға қойылатын талаптарды толық қанағаттандырады.

 Нанесение кишечнорастворимых покрытий на основе водшых растворов полиакрилатов

на таблетки

Резюме: В данной работе представлено сравнительное исследование трех пленкообразующих составов  под различными торговыми названиями (Kollicoat MAE 30DP, Kollicoat MAE 100P и ACRYL-EZE), в которых пленкообразователем является сополимер метакриловой кислоты с этиловым эфиром акриловой кислоты.

В результате проведенных исследований  изучена зависимость показателей качества таблеток от  составов модельных пленок: определена оптимальная концентрация полимера — 20% и пластификатора — 10%. Установлено, что таблетки, покрытые пленкообразующими составами Kollicoat МАЕ30DР и Acryl-eze, полностью соответствуют требованиям, предъявляемым Фармакопеей к кишечнорастворимым таблеткам.

COVERING THE TABLETS WITH ENTERIC COATING BASED ON WATER SOLUTIONS OF POLYACRYLATES