CAPSULES: A TEACHER’S COMPREHENSIVE GUIDE
Welcome, future pharmaceutical scientists and manufacturing professionals!
Capsules are solid dosage forms in which one or more medicinal and inert ingredients are enclosed in a small shell usually made up of gelatin. They are of various shapes and sizes, and contain a single dose of one or more active pharmaceutical ingredients. They are intended for oral administration. Capsules are also defined as “gelatin or methylcellulose shell designed to hold solids and liquids for oral administration”.
There are two types of capsules: hard and soft. The hard capsule is also called two-piece as it has two pieces in the form of small cylinders closed at one end. The shorter piece is called the cap which fits over the open end of the longer piece, called the body. Hard capsules are intended to contain solids. The soft gelatin capsule is also called one piece and is intended to hold liquids. Capsules are available in many sizes to provide dosing flexibility.
As a pharmacy educator with years of experience teaching pharmaceutics, I have observed that students often find capsule technology challenging. Let me tell you: Capsules are one of the most versatile and patient-friendly dosage forms—they offer excellent bioavailability and are ideal for masking unpleasant tastes.
In this comprehensive guide, I will walk you through the fundamentals of capsules—their merits, demerits, manufacturing processes for hard and soft gelatin capsules, filling techniques, sealing, polishing, and the differences between hard and soft capsules. By the end of this article, you will have a thorough understanding of capsule technology. Let us begin!
Dpharmguru’s exam insights:
Capsules are frequently tested in pharmacy exams. Remember: Hard capsules are two-piece and contain solids. Soft capsules are one-piece and contain liquids. Hard capsules are made by dipping process. Soft capsules are made by rotary die or plate process. Capsules offer better bioavailability than tablets. These are classic exam questions!
5.6. CAPSULES
5.6.1. Merits of Capsules
- They are tasteless, odourless, and can be easily administered
- They are used to enclose drugs having unpleasant odour and taste within the tasteless shell
- They can be filled quickly and conveniently; physician can change the dose and combination
- They are easy to handle and carry
- They can be produced in large quantities
- They are economic, attractive, and available in a wide range of colours
- They require minimum excipients
- They increase drug bioavailability by releasing the medicament at a specific pH
5.6.2. Demerits of Capsules
- They are not suitable for filling hygroscopic drugs as the drug may absorb water, rendering the shell brittle
- They are not suitable for concentrated solutions which require previous dilution
- They are not suitable for highly soluble substances like potassium chloride, potassium bromide, ammonium chloride
- They are also not suitable for highly efflorescent or deliquescent materials
- They demand special storage conditions
5.7. HARD GELATIN CAPSULES
Hard capsules have a rigid shell in two separate pieces fitted together, hence are also called two-piece capsules. The material types which can be filled into hard gelatin capsules are:
- Dry Solids: Powders, pellets, granules, or tablets
- Semisolids: Suspensions or pastes
- Liquids: Non-aqueous liquids
The large-scale preparation of filled hard gelatin capsules is divided into the following general steps:
- Formulation development and selection of capsule size
- Manufacturing of hard gelatin capsule shells
- Filling of hard gelatin capsule shells
- Sealing of hard gelatin capsules
- Cleaning and polishing of filled capsules
5.7.1. Manufacturing of Hard Gelatin Capsule Shells
The manufacturing process of two-piece hard gelatin capsule shell involves the following steps:
- Dipping: The sets of moulds (maintained at 22°C) are dipped into the gelatin solution
- Spinning: The moulds are slowly withdrawn with simultaneous rotation to obtain a film of uniform thickness
- Drying: The pins are passed through a sequence of furnaces with controlled humid air
- Stripping: The dried films are removed from the moulds through mechanical jaws
- Cutting: The bodies and caps are cropped to suitable dimensions by rotating blades
- Joining: The two parts are joined together to form a complete capsule
The machines are about 10 meters long, 2 meters wide, and 3 meters high. Each machine carries nearly 50,000 mould pins and produces more than a million capsules per day.
5.7.2. Filling of Hard Gelatin Capsule Shells
The filling process involves the following steps:
- Rectification: Empty capsules are oriented so that all point in the same direction, i.e., body end downwards
- Separation of Caps from Bodies: Depends on the difference in diameters between cap and body portions; vacuum pulls bodies down
- Dosing of Fill Material: Various machines are employed for filling (e.g., Lilly capsule filling machine)
- Replacement of Caps and Ejection: The cap and body portions are re-joined, and filled capsules are ejected
5.7.3. Sealing of Hard Gelatin Capsule Shells
- Gelatin Banding (Kapseals): Sealing with a coloured band of gelatin for tamper-evident capsules
- Heat Welding: Fuses the capsule cap to the body through the double wall thickness at their junction
- Thermal Bonding: Uses a liquid wetting agent that lowers the melting point and then thermally bonds at 40–45°C
Industrial capsule sealing machines are capable of producing 60,000–150,000 gelatin banded, heat welded, or thermally coupled capsules per hour.
5.7.4. Cleaning and Polishing of Filled Capsules
- Pan Polishing: Accela-Cota pan coating machines lined with polyurethane or cheese cloth
- Cloth Dusting: A cloth drenched with inert oil is used for rubbing the capsules
- Brushing: Capsules are introduced under rotating soft brushes to clean the dust from the surface
5.7.5. Merits of Hard Gelatin Capsules
- They have greater bioavailability in comparison to tablets
- Their drug releasing rate is much faster because of high solubility of gelatin shell
- They provide high degree of flexibility for formulations
- Their manufacturing is simple
- They involve less production steps
- They undergo less analytical tests
- They pose minimum risk of cross-contamination
- They mask unpleasant taste and obnoxious odour, aiding in patient compliance
5.7.6. Demerits of Hard Gelatin Capsules
- They are difficult to ingest very large doses of drug
- They are not suitable for drugs that dissolve the capsule shell
- They are not suitable for hygroscopic and deliquescent materials
- They are not suitable for highly soluble salts (iodides, bromides, chlorides)
- They involve rapid release of medicaments, may result in gastric irritation
5.8. SOFT GELATIN CAPSULES
Soft capsules or liquid gel caps are formed from liquid gelatin which is later hardened in a humid environment. Soft gel capsules are one continuous piece of gelatin. Soft capsules have thicker shells than hard capsules, and contain antimicrobial preservatives. The contents of soft capsules are usually solutions or suspensions of the API(s) in non-aqueous liquids.
5.8.1. Preparation Process of Soft Gelatin Capsules
The manufacturing process is divided into the following steps:
- Gelatin Preparation: Raw granular gelatin is mixed with glycerine and water. Glycerine acts as a plasticiser. The mixture is placed into a gelatin melter and heated until it turns into a molten liquid mass (~3 hours).
- Material Filling: Oil mixtures or pastes are prepared in processing tanks and moved into the hopper of the encapsulation machine.
- Encapsulation: Two techniques are used:
- Plate Process: A warmed sheet of gelatin is placed over a plate with depressions; vacuum draws the sheet into depressions; liquid medicament is poured; another sheet is placed; pressure seals and cuts capsules.
- Rotary Die Process: Two continuous sheets of gelatin are supplied to die rolls; fill material is injected through a metering device; capsules are shaped, filled, sealed, and cut continuously. Produces 25,000–30,000 capsules per hour.
- Drying: Two stages—tumble dryer (30–40 minutes) removes ~25% water; second stage in drying rooms for 24–48 hours until hard.
- Inspection: Misshaped, damaged, or not fully filled capsules are removed manually or by automatic sorting machines.
- Polishing: Tumbling is the most used production method to clean soft gel capsules.
- Packaging: Store at 20–24°C and 35% relative humidity.
5.8.2. Merits of Soft Gelatin Capsules
- They can be used for dispensing solids, liquids, suspensions, emulsions, volatile oils, semisolids, etc.
- Their disintegration is faster than hard gelatin capsules and tablets
- They are available in various sizes and shapes
- They can be easily swallowed as compared to hard gelatin capsules
5.8.3. Demerits of Soft Gelatin Capsules
- They cannot be used for hygroscopic, effervescent, and deliquescent drugs
- They cannot be used for acidic drugs, ketones, and aqueous products
- They cannot be used for drugs that cause stomach irritation
5.8.4. Difference between Hard and Soft Gelatin Capsules
| Aspects | Hard Gelatin Capsules | Soft Gelatin Capsules |
|---|---|---|
| In-House Development and Manufacture | Small Batches | Yes |
| Ability to Manufacture Humidity | Yes | No |
| Scale-Up | Simple and in-house | Requires large quantities and must be outsourced |
| Temperature of Fill | Max. ~70°C | Max. ~35°C |
| Plasticiser in Shell | No | Yes |
| Risk of Drug Migration | Low | High for drug soluble in plasticiser |
| Permeability of Shell to Oxygen | Low | High due to plasticiser and moisture content |
| Sensitivity to Heat and Light | Low | High due to plasticiser |
| Limitation on Excipients | High concentrations of hygroscopic excipients must be avoided | Hygroscopic excipients can be tolerated due to plasticiser |
Dpharmguru’s exam insights:
Hard vs Soft capsules are frequently tested. Remember: Hard capsules are two-piece, contain solids, have no plasticiser, and have low permeability. Soft capsules are one-piece, contain liquids, have plasticiser (glycerine), and have high permeability. Rotary die process is used for soft capsules. These are classic exam questions!
FREQUENTLY ASKED QUESTIONS (FAQs)
1. What is the difference between hard and soft gelatin capsules?
Hard gelatin capsules are two-piece capsules containing solids. Soft gelatin capsules are one-piece capsules containing liquids. Soft capsules have plasticisers (glycerine) in the shell, while hard capsules do not.
2. What is the rotary die process?
The rotary die process is used for manufacturing soft gelatin capsules. Two continuous sheets of gelatin are supplied to die rolls; fill material is injected; capsules are shaped, filled, sealed, and cut continuously. Produces 25,000–30,000 capsules per hour.
3. What are the advantages of capsules over tablets?
Capsules have better bioavailability, faster drug release, mask unpleasant taste, require minimum excipients, and are easier to swallow than tablets.
4. What is Kapseal?
Kapseal is a coloured band of gelatin used to seal the joint between the two parts of a hard gelatin capsule to make it tamper-evident.
5. Why are hygroscopic drugs not suitable for capsules?
Hygroscopic drugs absorb water from the gelatin shell, rendering it brittle and causing it to crumble into pieces, making the capsule unsuitable for use.
6. What is the role of glycerine in soft gelatin capsules?
Glycerine acts as a plasticiser in soft gelatin capsules. It makes the shell flexible and prevents it from becoming brittle.
SUMMARY
Capsules are a versatile and patient-friendly dosage form. This guide covered:
- Definition: Solid dosage forms with gelatin shells containing one or more APIs
- Types: Hard (two-piece) and Soft (one-piece)
- Merits: Tasteless, odourless, easy to administer, better bioavailability, minimum excipients
- Demerits: Not suitable for hygroscopic, deliquescent, or highly soluble drugs
- Hard Capsules: Manufactured by dipping process; filled with powders, pellets, or liquids; sealed by banding or heat welding
- Soft Capsules: Manufactured by rotary die or plate process; contain non-aqueous liquids; have plasticiser in shell
- Comparison: Hard capsules have no plasticiser, low permeability, and are filled at higher temperatures; soft capsules have plasticiser, high permeability, and are filled at lower temperatures
As I always tell my students: “Capsules are the bridge between patient comfort and drug efficacy—they make even the most unpleasant medicines easy to take.”
REFERENCES AND FURTHER READING
- Pharmacy Council of India (PCI). (2022). Pharmaceutics Syllabus. New Delhi: PCI.
- Indian Pharmacopoeia Commission (IPC). (2018). Indian Pharmacopoeia (8th ed.). Ghaziabad: IPC.
- Aulton, M. E., & Taylor, K. M. G. (2018). Aulton’s Pharmaceutics: The Design and Manufacture of Medicines (5th ed.). Elsevier.
- Allen, L. V., & Ansel, H. C. (2014). Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems (10th ed.). Wolters Kluwer.
- Lachman, L., Lieberman, H. A., & Kanig, J. L. (2018). The Theory and Practice of Industrial Pharmacy (4th ed.). CBS Publishers.
- Subrahmanyam, C. V. S. (2019). A Textbook of Pharmaceutics. Vallabh Prakashan.
Disclaimer: This article is for educational purposes only and does not constitute medical advice. Always consult qualified healthcare professionals for medical concerns. Pharmaceutical regulations and guidelines may vary by region—always refer to your local regulatory authorities for specific requirements.
written by:
Dr. N. Sujith Kumar
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