Sodium alginate as an alternative to shellac as enteric film coating for solid oral dosage forms

Enteric film coating for solid oral dosage forms provides a barrier that prevents acids in the stomach from dissolving or degrading any kinds of medication after oral dosage

Introduction

Enteric film coating of nutraceutical products can have multiple reasons like the requirement to protect the active ingredients or to avoid unpleasant smell after ingestion (e.g. garlic extract or omega-3 oil). Thus, it is important to modify the release in a manner that the actives withstand the acidic environment of the stomach (pH 1-4) and release only starts when reaching the small intestine (pH 5-7).

Individual reasons for the need of enteric protection are manifold (e.g. sensibility of the actives to the acidic environment in the stomach, leading to reduced or neutralised therapeutic effects, better adsorption rates in the small intestines, or causing of gastric mucous irritations). 1,2

Enteric film coating for solid oral dosage forms make this possible. It provides a barrier that prevents acids in the stomach from dissolving or degrading any kinds of medication after oral dosage. Biogrund offers enteric coatings for pharmaceutical as well as for food and nutraceutical industries.

The current film coating systems consist of pH-value controlled Methacrylacid/Ethyl Acrylate Copolymers or Hypromellose acetate succinates (HPMC AS) which enable an enteric protection. In addition, it also protects active ingredients against environmental influences such as light decomposition, oxidation and moisture. However, these polymers are not approved for food and nutraceutical products.

BonuLac is a natural shellac-based coating system, which provides a protective film with moisture sealing and enteric properties for food and nutraceutical products. With its taste masking properties it is recommended for the coating of natural extracts, oils and substances with unpleasant taste and odour. Even though shellac is a natural product, it does not comply with some clean label trends as it originates from the female lac bug and thus, is not vegan.3,4

Because of the increased demand for non-animal products by customers, the development of a vegan alternative to BonuLac for the food and nutraceutical industry was necessary.

In this study, we tested sodium alginate as an alternative to shellac based coating systems and developed a natural and vegan ready-to-use alternative for a user-friendly application.

Sodium alginate, also known as E 401, is the sodium salt of alginic acid, which is a polysaccharide. As Sodium alginate is extracted from the cell wall of brown seaweed it is a natural and plant based polymer. Moreover, sodium alginate is already established in the food industry as a thickener and coating agent. Also, it has a function as a gelling agent and forms a gel foam with gastric acid, which floats on the stomach content and forms a protective layer. This protective layer prevents the stomach acid from rising into the oesophagus. The undigested mixture is later excreted through the intestines. 5,6,7

AquaPolish F clear 190.02 E, which was the outcome of the studies that were performed, is a combination of sodium alginate with plasticisers and additional excipients. It is a ready-to-use, water-soluble film coating compound. Furthermore, it provides a protective film with enteric properties and gives a glossy effect to the surface of solid oral dosage forms.

Materials and methods

The composition and the quality of used raw materials and their functions are mentioned in Table 1. As sodium alginate is not available in qualities for the pharmaceutical industry, this product is only available for the food and nutraceutical industries.

Table 1: Qualities and functions of the components used in AquaPolish F clear 190.02 E

Because of the high viscosity of AquaPolish F clear 190.02 E (1100-1150 mPas; 10%, 20°C, 15 rmp, Brookfield) a solid content of 10% (wt%) was chosen. The enteric function was achieved with a weight gain of 15% (wt%). Coated tablets were prepared from tablet cores containing garlic extract and placebo cores.

Both, the tablets containing garlic as active ingredient and the placebos were coated with an ERWEKA coating pan. The used coating parameters are listed in Table 2. The form of the placebos was round (diameter: 1.3 cm; height: 0.2 cm), whereas oblongs were used for the garlic tablets (2.1x1.3x0.5cm).

Table 2: Used coating parameter for AquaPolish F clear 190.02 E

Disintegration tests were performed a day after the coating trial to allow complete curing of the film. The disintegration time of enteric-coated tablets was measured using a PTZ-S Pharma Tester. The method was identical to the European pharmacopoeia (Ph.Eur.) and conditions are listed in Table 3.

Table 3: Conditions of the disintegration test for AquaPolish F clear 190.02 E

To pass the test, oral dosage forms must be resistant in the already preheated 0.1 M hydrochloric acid for two hours. The oral dosage forms are not allowed to show any signs of disintegration or cracks, which might result in the release of the contents. After that, the acidic solution is replaced by a preheated phosphate buffer solution. The temperature is maintained at 37 °C. To pass the test, the release of the active has to be achieved within 60 minutes.

Furthermore, a stability study of tablets coated with AquaPolish F clear 190.02 E was performed. The coating was applied on tablets containing garlic extract as active agent. The conditions are listed in Table 4. A disintegration test was done every two weeks for a total of three months.

Table 4: Conditions of the stability study for AquaPolish F clear 190.02 E

Results

For the first trial placebos and tablets with garlic extract were coated with AquaPolish F clear 190.02 E. Table 5 shows the results of the disintegration test.

Table 5: Results of the disintegration test of AquaPolish F clear 190.02 E on placebos and tablets with active ingredient

The film coating did not disintegrate in the hydrochloric acid for two hours. In the buffer the coating disintegrated completely within the prescribed time.

The powder compound AquaPolish F clear 190.02 E could be suspended in water with a solid content of 10% and the round placebo tablets were given a slightly glossy surface after coating by the sorbitol used in the film coating compound. (Figure 1).

Figure 1: AquaPolish F clear 190.02 E in three different stages: R2U powder compound, suspended in water and applied on placebo tablets.

As Figure 2 shows, the disintegration (in buffer) of the coating decreased with increasing age of AquaPolish F clear 190.02 E. Nevertheless, all tablets survived the acid stage and thus, passed the disintegration test.

Figure 2: Disintegration of garlic tablets coated with AquaPolish F clear 190.02 E in the phosphate buffer (n=7)

Furthermore, pictures of the film coated tablets were taken before and after the stability study (Figure 3). The tablets after the stability study were a bit cloudier than before. However, this had no impact on the enteric function.

Figure 3: (A) Coated garlic tablet with AquaPolish F clear 190.02 E before the stability test. (B) Coated garlic tablet with AquaPolish F clear 190.02 E after 3 months of stability test

Conclusion

AquaPolish F clear 190.02 E is soluble in water and ensures a user-friendly application. Furthermore, it is able to mask odour and taste, provides a protective film with reliable enteric properties and does not originate from an animal source.

Because of the high viscosity of AquaPolish F clear 190.02 E, the solid content should be kept to a maximum of 10%. To achieve the function of an enteric protection the weight gain for tablets should be at least 15% based on tablet weight. Here we still see a need for process optimisation, which has prompted us to further develop sodium alginate based AquaPolish E formulations.

Also, the stability study showed that the coating maintains its function over a longer time in stress situations. Based on the results obtained in this study it has been proven, that sodium alginate is a suitable alternative for shellac based enteric coatings.

References

1. P.V. Kasture, S.A. Hasan, S.R. Parakh, S.B. Gokhale, “Processing of Tablets” in Pharmaceutics-I First year diploma in pharmacy, Pune, Arihant Printers, 15th Edition, 2008,

2. M. Kumpugdee-Vollrath, E. Gögebakan, J Krause, U. Müller, G. Weißmann. “Coatings in der pharmazeutischen Industrie, Magensaftresistente Coatings” in Easy Coating: Grundlagen und Trends beim Coating pharmazeutischer Produkte, Wiesbaden, Vieweg+ Tauber, 2001, p 53

3. H.Wen, K. Park ”Oral targeted drug delivery systems:enteric coating” in Oral controlled release formulation design and drug delivery, New Jersey, John Wiley&Sons, 2010, p.206

4. N.Karak, “Biopolymers for paints and surface coatings” in Biopolymers and Biotech Admixtures for Eco-Efficient Construction Materials, Woodhead Publishing, 2016

5. M. Kumpugdee-Vollrath, E. Gögebakan, J Krause, U. Müller, G. Weißmann. “Alginate” in Easy Coating: Grundlagen und Trends beim Coating pharmazeutischer Produkte, Wiesbaden, Vieweg+ Tauber, 2001, p 191-193

6. https://www.test.de/medikamente/wirkstoff/antazidum-gelbildner-kaliumhydrogencarbonat-natriumalginat-kombination-w274/ 01.07.2020

7. https://www.gaviscon.de/so-wirkt-gaviscon/natuerlicher-wirkstoff-alginat/ 10.07.2020

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