A comparative analysis of soft vegetable capsules: Taking your brands with Versagel™ to the next level

Carol Helena Aguilar Rodríguez – Pharmaceutical Chemist, Procaps SA

Carolina Quintero Ochoa – PhD Polymer Science and Engineering, Procaps SA

Abstract

In the following document, a study and comparative analysis of different soft vegetable capsules is presented for dietary supplements. Versagel™ and other 4 commercial references were evaluated and compared to determine their performance. One of the main challenges encountered in this technology is the obtainment of an adequate seal thickness or high seals which helps assure good shelf-life stability in hotter and highly humid zones.

From the characterization carried out, and the analytical evaluations at month 0 (initial) and accelerated stability (40°C - 75% RH) at month 1, it is concluded that the Versagel™ technology developed by Procaps can offer an excellent alternative for soft vegetable capsules for dietary supplements with superior performance to other products found in the international market.

From the characterization carried out, and the analytical evaluations from month 0(initial) and after one month of accelerated stability (40°C - 75% RH), it has been concluded that the Versagel™ technology developed by Procaps can offer an excellent alternative for soft vegetable capsules for dietary supplements with superior performance to other products found in the international market.

Introduction

The pharmaceutical industry is in constant search of solutions for different pathologies and/or diverse populations. Hence, it has been involved in the constant development of alternatives for soft gelatin capsules, which can meet new needs and challenges of upcoming markets and trends.

Procaps, as part of the pharmaceutical industry, has dedicated itself to study and develop Versagel™ technology, offering soft capsules of vegetable origin as an alternative and solution for religious and ethnic groups or populations with dietary restrictions. For this purpose, various starches (vegetable polymers) have been tested to replace gelatin which comes from an animal source. The use of these vegetable polymers not only allows us to offer a vegan product but also results in a product with certain advantages over conventional softgels. Some of the advantages are:

Avoid capsule shell crosslinking during its shelf life.

• Improve stability when using fills with extreme pH values ​​or high ionic strength.
• Allow the encapsulation of fills that require high temperature for an adequate encapsulation.
• Solve complex formulation challenges.

With Versagel™ technology now available, we can discover new ways to take soft gelatin capsules to a next level.

Objective

The objective of this paper is to compare our Versagel soft capsules with other products that are currently offered in the international market. This comparison was done through the characterization and evaluation from an initial month and after one month of accelerated stability (40 ° C - 75% RH).

Materials and Methods

Various analytical tests described below were carried out on all references of vegetable soft capsules:

• Visual Inspection

Visual inspection and reporting of the capsule´s characteristics such as: good appearance and shape, absence of leakers (leakage through the seal), visually acceptable seal, uniform color, and no presence of clumping (agglutination) when subjected to accelerated stability were evaluated.

Additionally, the shell materials declared on the label for commercial references and the materials used for Procaps´ soft vegetable capsules are described.

• Seal Thickness (%)

The % seal was determined with the use of a LABOMED Microscope (Software PixelPro). The capsules were cut to obtain a ring that was used to measure the thickness of the shell wall and seal.The % seal was determined by dividing the seal thickness by the shell wall thickness. Five samples were evaluated for each product and the average was reported. It is important to consider that % seal above 40% is important in order to prevent leakers or even capsules bursting during its shelf stability.

• Disintegration (USP Option 2)

For capsule disintegration, an acetate buffer 0.05M was used and it was performed in the 1000mL Apparatus 2 at 50rpm and 37°C. Six samples were analyzed per product (1 per glass). The accepted criteria was the USP <2040> Disintegration and Dissolution of Dietary Supplements which states that the capsules need to disintegrate in less than 60 minutes to pass the test.

• Hardness (N)

For this evaluation, a Bareiss brand gelatin durometer was used (digi test, weight: 20 N). Ten capsules were evaluated, and the average was reported.

Results

• Visual Inspection

All capsules have good shape, uniform color, and visually acceptable seal. None of them show leakers or clumping at the initial month of study or at month 1 of accelerated stability.

Shell and fill ingredients for each product are presented below. For the market products, the ingredients correspond to the materials declared on the label.

Shell and Fill Ingredients

• Seal Thickness (%)

In general, all but one reference (#3) presented good seals (over 40%). Versagel, showed the highest seals (59-70%) which, is one of the main challenges in this technology. Even though having % seals below 40 does not mean that leakers will be present, the higher the seal, the better off you are for shelf-life stability.

Seal Thickness at Initial Month (M0) and after 1 month (M1) of accelerated stability

• Disintegration (min)

The results for the disintegration test, shows compliance for all products. The acceptance criteria (<60 minutes) during initial month (gray bars) and the accelerated stability at month 1 (blue bars) show a disintegration time below 40 minutes for all samples. In the graph, it can be seen, that reference 4 and the Versagel product have the lowest disintegration time with 9, 8, 10, and 13 minutes for month 0 and month 1 respectively. In addition, it can be observed, that the results between month 0 and month 1 do not present significant differences indicating good stability for all products.

Disintegration Time (minutes) at Initial Month (M0) and after 1 month (M1) of accelerated stability

• Hardness (N)

All the references under study have low hardness compared to soft gelatin capsules which usually have 9 to 13N hardness. This is due to the type of polymer used for each capsule. Gelatin develops a harder shell than stach polymers. As can be seen in the graph, results are presented between 2.1 N and 3.7 N at the initial month and in accelerated stability between 1.8N and 3.4N. As mentioned before, none of the product shows leakers or clumping during accelerated testing and the capsules retain their initial shape.

All the references under study have low hardness compared to soft gelatin capsules which, usually have 9 to13N hardness. This is due to the type of polymer used for each capsule since, gelatin develops a harder shell than stach polymers. As seen in the graph, results present a hardness between 2.1 N and 3.7 N at the initial month and between 1.8N and 3.4 N in accelerated stability. As mentioned before, none of the products shows leakers or clumping during accelerated testing, and the capsules retain their initial shape.

Hardness at Initial Month (M0) and after 1 month (M1) of accelerated stability

Conclusions

From the results shown above, it is evident that Procaps can offer a vegetable soft capsule alternative for dietary supplements with the advantage of high seals and overall good properties during accelerated aging.

Versagel™ technology, is a platform developed by Procaps which allows our customers to offer different fill formulations in soft capsules (high temperature, high pH, use of APIs that enhances crosslinking of gelatin capsules) and, at the same time, can declare itself Vegetarian and Vegan for new lifestyles that are merging in the market as trends.

Our R&D and commercial team are excited to collaborate and take Versagel to the Next Level.

About Procaps Group

Softigel® by Procaps is a leading provider of Contract Development and Manufacturing services in softgel advanced technologies for the global pharmaceutical and nutraceutical industry. Through our extensive capabilities and deep expertise in product development and softgel manufacturing, we help different companies bring innovative products to their markets faster, offering their patients and consumers an exceptional experience, high preference and superior adherence to different therapies.  Our advanced delivery technologies, including Softgel and related technologies, our proven formulation, manufacturing and regulatory expertise, has enabled us to become an integrated CDMO (iCDMO), giving customers full-service, turnkey solutions in prescription drugs, OTC and dietary supplements across both development and delivery.  

For more information visit www.softigel.com or contact us at [email protected]