You cannot invest in the Softgel industry without proper knowledge on soft gelatin capsule formulation.
It doesn’t matter whether you want to invest in the CBD oil Softgel, food supplement Softgel or medicine Softgel.
You must know exactly what soft gelatin capsules are made of.
Consequently, in this piece, we shall discuss several issues about the soft gelatin capsule.
Here is a glimpse of what you should expect benefits, ingredients, classification formulation techniques, formulation equipment, and many more.
Let’s kick off our discussion immediately.
Soft Gelatin Capsule Definition?
Before diving into the definition, in the pharmaceutical industry, you will notice that practitioners administer medications differently.
The most common dosage forms include tablets and capsules.
The capsules are tiny and cylindrical while the tablets vary in shape and are compact.
Again the capsules could be classified into gelatin and vegetarian.
Still, we can classify the gelatin capsules into two classes, namely soft and hard.
Now, let’s indulge in our fundamental question.
What is a Soft Gelatin Capsule?
Therefore, a soft gelatin capsule exists in a single or a unit piece, i.e. outer soft shell or solid capsule which holds the active medication.
This covering usually melts quickly once in the stomach region.
Soft gelatin capsules
The usually smooth capsule shell comprises of a gelatin material hence the name soft gelatin capsule.
The shell encloses the primary medicinal values together with active ingredients.
It’s especially suitable for use when handling medication ingredients that comprise majorly of oils, liquid, semi-solid or oil-soluble drugs.
So generally, they comprise of liquids, unlike the hard gelatin type.
Additionally, the soft gelatin capsules assume various shapes but mostly oval, spherical, and oblong.
Interestingly, they never have an exact proportion.
During the encapsulation process, the pharmacists appropriately mix the drugs with the right quantities of the solvent which exist inside the outer shells.
Optionally, the outer shell, content, or even both the two could comprise of an active component.
Note that the major component may exist in solution form, some in suspension or emulsion form.
All these ways provide a faster means of absorption of the active constituent compared to other delivery methods in the tablet.
Indeed soft gelatin capsules are very popular in the pharmaceutical sector due to those unique traits.
Additionally, soft gelatin capsules bring several advantages associated with the delivery of drugs.
Next, we move further to explore the benefits of soft gelatin capsules.
Benefits of Soft Gelatin Capsules
The following are the advantages of using soft gelatin capsules.
- It enhances the quick absorption rate of the drugs. The outer shell duly dissolves in the stomach releasing highly absorbent medicinal value which would, in turn, induce a rapid action in the body.
- Soft gels provide a better alternative of administering poorly soluble drugs through the injection of a liquid batch aimed at faster solubility.
- Soft gels improve the bioavailability of drugs.
- It’s useful in delivering a lowly component dosage of medicinal compounds such as those for the potent drugs, thereby decreasing its plasma variability. This technique suit doses less than 100 microgrammes.
- Soft gels mask the tastes and nasty odors of the active ingredient hence enhancing the oral intake by the patients.
- More comfortable to swallow due to its soft texture and flexible shapes unlike tablets and you don’t necessarily require accompaniment such as water.
- Through the unique properties of its outer shell, the soft gels harbor the active component from the harmful direct ultraviolet rays which may initiate oxidation of the material.
- The gelatin shell provides an airtight and safer enclosure of the fill material.
- The soft gels have got very precise and accurate content, thus delivering the intended dosage of the medicine.
- Soft gels have got an unusual and pleasing appearance.
- It ensures the complete encapsulation of primary ingredients, thereby providing a tamper-proof system.
- The soft gels are customizable to release its contents at a specific location in the gastrointestinal tract.
- Colors, shapes, laser etching, and sizes are all easily customizable with soft gels.
However, these several benefits tend to overshadow the shortcomings of the soft gels.
Indeed, they also have a share of their criticism.
CBD Soft gelatin capsules
- Only a few genuine manufacturers of soft gels exist across the globe due to some constraints.
- Preparations of the soft gels are quite costly since it’s only limited to large scale due to the high tech equipment involved.
- Soft gels are very thermal and moisture sensitive. It, therefore, means that you should be vigilant when storing them, especially in hot or humid climatic regions. Otherwise, they may stick or burst open.
- They pose dietary restrictions. The gelatin material is hugely cow or pig bones and skins. Unfortunately, some religions such as Jews, Muslims, and Hindus discourage the consumption of such animal products. Besides, the total vegetarians don’t easily use them.
Now you already know the reasons why most pharmaceutical industries are increasingly opting for soft gels.
We already implied that soft gels hugely rely upon the gelatin material.
Besides the gelatin, other materials play a significant role in the manufacturing of the capsules.
So what are these ingredients?
Keep on reading to learn more about that in the next segment.
Ingredients of Soft Gelatin Capsules
You must be now aware that a whole soft gel capsule comprises of an outer shell and a fill material.
Each of these compartments has got its unique composition.
We shall now analyze every possible constituent of the entire capsule parts.
Structure of soft gelatin capsules
1. Outer Shell of Soft Gelatin Capsules
It forms the most basic component of soft gelatin capsule formulation.
The shell comprises a host of components; the major ones include gelatin, plasticizer, a mixture of plasticizers and water.
Moreover, it may consist of preservatives, coloring agents, opacifying agents, flavorings, sweeteners, gastro-resistant products, etc.
You realize these constituents are numerous, meaning we can’t delve into all of them in this guide.
For the sake of our discussion, we shall focus on the significant elements.
· Gelatin for Soft Gelatin Capsule Formulation
Gelatin is a tasteless organic food material comprising collagen.
Animals are the prime source of this extract.
You can mainly derive it from the animal bones and skins.
Scientists reportedly prefer acquiring such products from the pigs and cows.
Of course, synthesizing gelatin from the bones and skin isn’t that straight forward process.
You would require to do this in a pharmacy with the aid of some equipment, a specialist would make the task easier.
Subsequently, due to the difference in the production of the gelatins, two main types are available.
The first type involves the production of gelatin by hydrolyzing the animal skins by the aid of the acidic solution.
Whereas the next one consists of the production by use of basic hydrolysis of bovine bones.
Importantly, with the advancement of technology, a proper substitute for the gelatin capsule is available.
The vegetarians and religious folks can now opt for vegetarian capsules made from pure plants and vegetative products.
That should be a reprieve to the vast number of such people.
· Plasticizers in Soft Gelatin Capsule Formulation
Have a close look at the soft gel; you will notice its’ smooth, elastic, and pliable outer cover.
These attributes are only possible by the use of an appropriate plasticizer.
Plasticizers significantly account for a large proportion of the capsule — usually, approximately 20 – 30 % of the soft gel.
Structure of Softgel – Photo courtesy: Mahesh
The commonly available plasticizer is glycerol.
Apart from that, many pharmacists use sorbitol and propylene glycol- 400 but only after mixing with glycerol.
The contributions of plasticizers to the final product are very crucial, so you need to be very vigilant to get it right.
The texture, dissolution, and disintegration of the eventual soft gel would vary depending on the kind of the plasticizer you use.
In fact, it may have an impact in altering its physical and chemical stability.
The bottom line is, the right plasticizer type and its concentration should guarantee adequate compatibility of the shell and the fill material.
· Water in Formulation of Soft Gelatin Capsules
Water is an undeniably essential part of the shell. It occupies a large chunk of about 30 – 40 % of the formulation.
Water is a crucial solvent for processing, specifically in the preparation of the gel together with encapsulation.
This water content provides enough turgidity to the capsules.
This stability comes in hand during fluctuation in the storage conditions where the capsules need to maintain their physical properties.
· Opacifiers in Soft Gelatin Capsule Formulation
In cases, whereby the fill formulation is suspension or even light sensitive, then you may use an opacifier preferably titanium dioxide.
The opacifier initiates the formation of a thick cover.
Furthermore, it disrupts any potential photodegradation of the light susceptible ingredients.
Using Titanium oxide as individual constituent results in the formation of a white but opaque shell.
Elsewhere, when you incorporate other substituents, then you get a colored one.
· Colouring Agents for Soft Gelatin Capsules
Colorants perform a direct task; they give the shells your intended color, which will, in turn, help you to identify your capsules quickly.
Different colors of Softgel capsules
Note that, colorants are available in two options, i.e., synthetic and natural.
Selecting between the two shouldn’t be a tough task.
It all depends on the customer’s preference or bias towards synthetic products or natural ones.
· Preservatives in Softgel Capsules Formulation
Preservatives are in tiny quantities, yet they serve a vital function. Common ones are methylparaben or propylparaben.
They keep in check the drug medicinal value and keep away any impending interference from microbes.
Preservatives contribute to approximately as low as 0.2 % of the concentration of the entire medicinal capacity.
· Flavoring Agents in Soft Gelatin Capsules
Remember, we earlier on indicated that soft gels mask the unpleasant taste of the drugs.
This is possible, thanks to the flavoring agents.
You have a long list of these products to select. Notable examples are essential oils, ethyl vanillin, sucrose, etc.
2. Fill Material in Soft Gelatin Capsule Formulation
Unlike the shell, the formulation of the fill is unique and vary accordingly to the needs of the manufacturer.
Meaning, each fill material is diverse on its specialty to achieve the intended optimal therapeutic value.
During the formulation, you have to reconsider the chemical stability of the active ingredient seriously.
Doing this is not only a conventional manufacturing procedure but also above all, it improves the bioavailability of the drug.
Aside from that, any conventional fill exists in three primary types.
Have a look.
i. Neat components such as oily liquid
It doesn’t end there; you have to use an efficient filling technique that guarantees accurate measurement while achieving a stable capsule.
That’s it. Those are your target ingredients of every soft gel capsule.
The next segment is equally informative and technical in equal measure. You can’t miss that.
3. Soft Gelatin Capsule Formulation Techniques
During the formulations, you need to uphold extreme care and vigilance because this is a challenging technical procedure.
Here is an essential design of the soft gel formulation that you don’t rule out.
Always make sure that the interaction or the migration between the liquid/ semi-liquid fill and the outer shell is very negligible.
Now it’s at this point that the choice of the type of plasticizer plays an integral role.
Therefore, it’s these shell and fills interactions that the formulation techniques seek to identify and prevent.
Again, such interactions are most prevalent during the manufacturing process, drying, or storage.
The ability to identify and control the degree of these interactions is a plus for you.
This kind of interactions compromises the stability of the final product.
With all that in mind, we can now dive into the two agonizing types of interactions.
They are as follows.
- Chemical reactions
- Physical interactions
Softgel capsules manufacturing – Photo courtesy: BIOPHARMA ASIA
I will break down each into a simple discussion for uncomplicated understanding.
· Chemical Reaction in Softgel Capsules Formulation
A chemical reaction involves the several reactions that may occur between the fill matrix against the gelatin and the plasticizer.
So generally, it involves the components of the fill matrix together with the outer shell ingredients.
Take, for example, during the encapsulation process; gelatin may undergo crosslinking if the active ingredient comprises of reactive groups of elements such as aldehyde.
You can solve this problem by only using succinylated gelatin.
Another scenario of reaction occurs as a result of esterification and transesterification of medicine that contains polyols as an element.
The good news is that you can also limit this reaction.
Regularly use a glycerol free shell formulation; this is because of glycerol is highly reactive compared to other polyols.
If not, you may add a correct quantity of polyvinyl pyrrolidone to the fill matrix.
Note that the chemical reaction isn’t only limited to these two case scenarios; they may vary depending on the chemical elements of the soft gel.
What you need to do is always consult a renowned manufacturer whenever you’re not sure of the solution.
· Physical Interaction in Softgel Capsules Formulation
Basically, physical interaction in the soft gel occurs due to the constant movement of the fill elements as a whole in the shell.
Likewise, the action could be through the outer cover.
Still, it could occur via the shell or in the fill matrix.
Now the degree of the physical interactions of the outer shell and fill ultimately depends on two factors.
They include the type and suitability of the chemical composition of both the outer cover and fill.
Additionally, the quantity of specific components is another fundamental factor.
A typical example being the amount of water.
Always maintain the water content of the fill at a critical value not exceeding approximately 5 %.
There you have it. Remember, the measure of success of your manufacturing process is directly proportional to its ability to minimize these interactions.
Apart from the techniques, you have to be aware of the equipment involved.
Our next section focus on the formulation equipment.
Stick with me.
Soft Gelatin Capsules Formulation Equipment
Various methods are available for conducting the formulation process. Some of them include:
- Rotary die process
- The plating process
- Reciprocating die process
- Alcogel process
- Seamless gelatin capsules.
Nevertheless, we shall stick to the Rotary die process.
The procedure takes place in the Rotary die equipment.
Softgel capsules encapsulation machine
And, by the way, just in case you need this machine and other related accessories, you can check this: Soft Gelatin Capsules Encapsulation Machine and Equipment.
Allow me to take you through the working mechanism of the rotary die.
i. Feed the two gelatin ribbons continuously into the assembly of the rotating die.
ii. The rotary die then forms the two ribbons into two halves for a complete capsule.
iii. After that, the ribbons now converge beside to the fill injector.
iv. The fill injector accurately measures and introduces the required volume of the fill matrix into the capsules. The nozzle has got a pump which initiates the flow of material.
v. After that, a pulley system transfers the full capsules to the sealing chamber. During this process, the die assembly rotates.
The above process is a complete process for the encapsulation.
During the above process, you need to take regulate the following parameters: gelatin and fill temperature, ribbon thickness, seal width, fill quantity.
vi. Afterward, drying follows. Transfer your capsules onto the tumble drying tunnel. This section has an optimum temperature and compressed air.
vii. Once the capsules are adequately dry, move them into a low humidity room for another cycle of drying.
It’s essential to monitor the following parameters during drying: gelatin moisture level, fill moisture, and capsule hardness.
The main objective of drying is to ensure the attainment of the moisture level of about 6 – 8% by the gelatin shell.
The process doesn’t stop at this point.
You certainly have to guarantee the suitability of the soft gel capsules.
The final procedure entails several finishing measures undertaken on the products.
viii. Pick the soft gels and sort them according to sizes.
ix. Inspect the products to remove damaged ones.
x. Now you can polish and clean the soft gel capsules to remove any unwanted materials on the capsule surface such as glycerine or oil.
xi. Finally, pack the soft gels under optimum conditions, i.e. Temperature range of 20 – 28°C. The relative humidity should be of about 40 %. These conditions improve the stability of the soft gels.
In summary, the soft gel formulation process boils down to a series of steps.
i. Preparation of Gelatin
ii. Preparation of the fill material
Let’s move into our next aspect of the discussion.
Classification of Soft Gelatin Capsules
We can group the soft gels into two broad categories, ie.
- Type A
- Type B
Different sizes of soft gelatin capsules
· Type A
The A category soft gels are achievable by the acidic hydrolysis process on the precursor of the isoelectric point of Ph-9.
The Pork skin is the primary source of this soft gel.
· Type B
Unlike the type A, you can manufacture the B type from alkali hydrolysis on a precursor that displays an isoelectric point at Ph-4.7.
Animal bones are the excellent sources of manufacturing this kind of soft gel.
You have it all now.
I am sure you have learned a lot regarding the soft gel capsule formulation.
Obviously, with the increasing demand of the soft gel, a lot of advancements are already out about optimizing the bio performance of the capsules.
Above all, you now understand the formulation process.