SoftGel Capsules | Gelatin Capsule | SoftGels Dosage Form

Overview of softgels manufacturing & softgel technologies for the solubility, stability & bioavailability enhancement of soft gelatin capsules.

Q1. What is a softgel or soft gelatin capsule?

Soft gelatin capsules (softgels) are capsule shells surrounding a liquid or semi-solid fill. An active ingredient can be incorporated into the capsule shell, the inner liquid/semi-solid fill, or both. Softgel unit dose solid dosage forms feature an easy-to-swallow capsule shell that is tamper-resistant, facilitates odor and taste masking, and is available in a broad range of shapes and colors.

Properties of soft gelatin capsule shells:

Gelatinous: Softgel capsule shells are composed of dry gelatin, formulated to have 30-40% glycerol.

Oxygen Permeability: Capsule shells offer protection against diffusion of oxygen into drug products by acting like a barrier.

Residual Water Content: Softgels contain residual water and compounds susceptible to hydrolysis which are protected, if dissolved or dispersed in an oily liquid fill.

Presence of Iron: Iron is present in raw gelatin, however, it is limited to 15 ppm..

Bloom or gel strength: It ranges from 150g to 200g.

These properties, amongst others, enable softgel dosage forms to offer several advantages over other oral dosage forms. They are designed to solubilize and improve the oral bioavailability of poorly soluble compounds, deliver low and ultra-low doses of a compound, deliver a low melting compound, and minimize potential generation of dust during manufacturing.

Soft gelatin capsules offer additional benefits including, but not limited too:

- Portability

- Faster action of drugs

- Ease of administration

- Color, size & shape (oblong, round, oval, etc.) variability

- Stability enhancement

- Increased solubility & improved bioavailability of drugs

- Liquid soft gelatin encapsulation

- Specialized dosage forms

E.g. Chewable softgels, suckable softgels, twist-off softgels, meltable softgels, extended release softgels, etc.

These features and benefits offered by softgel dosage forms make them increasingly popular for pharmaceutical, cosmetic, and nutritional formulations. Market Research Future’s (MRFR)’s study suggests that the global softgel capsule manufacturing market is expected to strike a CAGR of 5.46% during the forecasted period 2018 to 2023. The report further highlights that the softgel market value is likely to grow from USD $2,381.90 million in 2017 to USD $3,276 million by the end of 2023.

Q2. What are the different components (ingredients) of soft gelatin capsules?

Soft gelatin capsules consist of an outer fill (capsule shell) and an inner fill (oily mixture, solution, or suspension). These soft gelatin caspule ingredients are explored, in detail, below.

Capsule Shell or Outer Fill - Soft Gelatin Capsule Ingredients

1. Gelatin: (E.g. Bovine, Porcine, Piscine or Vegicap alternatives)

Gelatin is an animal protein made by boiling the collagenous material from animal bones, hides, and skin. Depending on its source, gelatin can be divided into two types; Type A, from acidic hydrolysis of animal skin, and Type B, from basic hydrolysis of bovine bones.

Gelatin is one of the most crucial soft gelatin capsule ingredients and can only be used once it has been approved by regulatory authorities. Furthermore, approval is only granted when it satisfies minimum specifications relating to gel strength, viscosity, particle size distribution, etc.

Now, there is a vegetarian alternative - vegicap soft capsules - which are derived from carrageenan, an all-natural, plant-based seaweed extract. Vegicap soft capsules enable the drug product to appeal to more consumers with dietary restrictions. Vegicap soft capsules also offer the following advantages; they are tasteless, easier to swallow, and quick to absorb.

2. Plasticizer: (E.g. Glycerin & Sorbitol)

Plasticizers are used mainly for oral solid dosage forms to facilitate oral pharmaceutical applications. Plasticizers are added to polymers used as film forming agents in order to make them pliable and soft, thereby enhancing the flexibility and plasticity of the films. In case of soft gel capsules non-volatile plasticizers that complement gelatin molecules are used.

3. Solvent: (E.g. Water)

Water is used as a solvent in soft gelatin capsules. Water forms a very crucial soft gelatin capsule ingredient of the outer shell. As a show of its importance, water occupies about 30 – 40 % of the overall wet gel formulation. It further compliments the processing procedure, especially during gel formulation and soft gelatin encapsulation.

4. Opacifiers: (E.g. Titanium Dioxide)

Opacifiers provide protection against light and photodegradation. They also play a role in concealing the soft capsules’ inner fill contents.

5. Preservatives: (E.g. Antioxidant, Antimicrobial & Chelating Agents)

These agents play a role in the preservation of soft capsule contents, which increase their shelf life and make soft-gels safe for consumption.

6. Flavorings: (E.g. Essential oils, Sucrose, etc.)

Flavoring agents are used to achieve taste masking in solid dosage forms (softgel capsules, tablets, etc.) in order to make them more suitable and acceptable for ingestion.

7. Colorants: (E.g. Dye, Lakes, Mineral Colors, etc.)

Coloring agents can impart various colors to softgel dosage forms. Colorants play an important role in improving patient compliance and can be further selected to complement the disease being treated.

8. Other Additives

Liquid/Semi-solid Inner Fill - Soft Gelatin Capsule Ingredients

1. Oily Mixtures (E.g. Undiluted Mineral or Vegetable Oils)

Oily mixtures may be referred to as neat substances since they purely consist of oily liquids. A neat substance is a sample which is conducted in a liquid phase, without any solvent.

2. Solutions (E.g. Soft gelatin capsule ingredients - Polyethylene Glycols)

Oral solutions are clear liquid preparations for oral use containing one or more active pharmaceutical ingredients (API) dissolved in a suitable medium (solvent).

3. Suspensions (E.g. Soybean Mixed with Beeswax, glycerides, etc.)

Suspensions are widely used liquid dosage forms. They may be defined as preparations containing finely divided drug particles (active ingredients) distributed somewhat uniformly throughout a medium in which the drug exhibits a minimum degree of solubility.

Q3. What is soft gelatin technology?

Soft gelatin capsule technology enables the production of unit dose solid dosage forms referred to as soft gelatin capsules. Soft gelatin technology is a technology for bioavailability enhancement of poorly soluble molecules. Soft-gelatin capsule technologies further enable various oral pharmaceutical applications and offer numerous advantages that can bring superior compounds to market faster. Soft shell capsule manufacturing processes, supported by soft-gelatin technologies, progress in seven steps.

Steps Involved in Soft gel Manufacturing or Soft Gelatin Capsule Manufacturing:

Step 1: Raw Material - Storage & Selection

Step 2: Weighing Soft Gelatin Capsule Ingredients - Inner & Outer Fills

Step 3: Preparation - Inner Fill Material & Soft Shells

Step 4: Soft Gelatin Encapsulation

Step 5: Softgel Dosage Form Inspection

Step 6: Soft Shell Capsule Packaging

Step 7: Finished Product Storage & Distribution

Soft gelatin technologies provide further applications and advantages, apart from bioavailability enhancement. These benefits imparted by soft-gelatin technologies are listed below.

- Soft-gelatin capsule technologies produce unit dose solid dosage forms, which reduce dosage variability.

- Formulations produced by soft gelatin technology have rapid onset of action and can be effective even with a reduced API load.

- Serialization and track-and-trace soft-gelatin capsule technologies enable accountability and traceability of products throughout the pharmaceutical supply chain.

- Softgel solid dosage forms have lesser side effects and improved therapeutic effects.

Recent soft-gelatin capsule technology advancements have made today’s softgels (soft shell capsules) even more convenient and more effective for consumers, and it is well equipped to hold its own against newer formats. Soft shell technologies for bioavailability enhancement and other benefits, will continue to evolve with new advancements in softgel equipment, soft gelatin ingredients, liquid filled hard capsule techniques, oral pharmaceutical applications, and other softgel dosage form developments.

Q4. What are the steps involved in soft gelatin encapsulation?

The fourth stage of soft gel manufacturing, soft gelatin encapsulation, is the process of converting gel mass into a thin layer of gelatin and wrapping it around the inner fill material to form a softgel unit dose solid dosage form. Before commencing encapsulation, manufacturers must choose the appropriate softgel encapsulation machines for their chosen soft gel manufacturing projects.

Equipment is thus selected according to the requirements of the capsule manufacturing projects, however, softgel encapsulation machines also have to fulfill additional criterias in order to be selected; (1) Softgel encapsulation machines must conform to GMP standards, (2) Softgel encapsulation machines must have the right features & specifications, (3) Softgel encapsulation machines should be easy to maintain & operate, and (4) the selected technologies should facilitate bioavailability enhancement. After the raw materials have been weighed and prepped, and the appropriate soft gel encapsulation machine has been selected, encapsulation may commence.

Encapsulation is completed in the five steps noted below:

Step 1: The prepared inner fill and outer fill materials are transported to encapsulation bays.

Step 2: Each encapsulation capsule manufacturing machine is segregated into individual bays.

Step 3: Molten gel is pumped into the machines.

Step 4: Two thin ribbons of gel are formed, on either side of the soft gel manufacturing encapsulation machines.

Step 5: The ribbons are passed over a series of rollers and dies that help in determining the size of the capsules.

Following encapsulation, the resultant compounds are tumble dried, cured via supplemental drying, sized, inspected, and finally packaged, after which the soft gel capsules are ready for storage and distribution.

Q5. Who are the leading soft gelatin capsule contract manufacturers in the industry?

The leading contract manufacturers offering soft gelatin capsule manufacturing services are:

Capsugel

Capsugel is an pharmaceutical empty capsules manufacturer that has more than 20 years of experience in hard gel & soft gel technologies. Capsugel thereby offers a range of empty capsule (empty hard gelatin capsules) and softgel capsule formulation solutions. Capsugel provides color combinations that suit both the product indication and customer preferences.

Furthermore, SGcaps® - their one piece capsule, features an easy-to-swallow shell consisting of plasticizers (glycerin, sorbitol, PEG) that meet all cGMP guidelines, FDA and MEA purity standards and feature a Certified QA system for traceability of raw materials.

Suheung Capsule

With over 30 years of experience in contract manufacturing services for pharmaceutical empty capsules, softgel capsules, empty hard gelatin capsules, empty HPMC capsules, and more, Suheung Capsule has mastered the fundamentals and acquired a unique know-how in contract manufacturing/OEM production. Their dedicated R&D center for contract manufacturing services can assist from product conceptualization to final realization. Suheung’s quality products are supplied as bulk or packaged products, which includes softgels.

ACG Worldwide

ACG is the largest pharmaceutical empty capsules manufacturer offering end-to-end manufacturing solutions for the pharmaceutical industry. Their process solutions include filling machines for capsules containing everything from powders to liquids. Additionally, customers get all the support they need to select the right capsule-type filling method for products such as pharmaceutical empty capsules, including empty hard gelatin capsules and empty HPMC capsules. Furthermore, their new generation GK SoftGel Encapsulation line is ideal for medium scale softgel manufacturing.

Qualicaps

Qualicaps® is a trusted delivery vehicle for products that promote healthcare. Qualicaps’ technology and product portfolio to complement the needs of solid oral dosage production include empty capsules, HPMC capsules, and softgel machines. Moreover, as an empty capsules manufacturer, they offer a development and design team to customize equipment for specialized needs and a Technical Services team to help troubleshoot filling and sealing issues.