NTA Level 6 • Semester 1 • PST06103

Soft Gelatin Capsules

Pharmaceutical Production • Source Session/Topic 14

Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability.

Session 14: Soft Gelatin Capsules

Total Session Time: 120 minutes

Pre-requisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Define soft gelatin capsules

• Explain the composition of soft gelatin shell

• List the advantages and disadvantages of soft gelatin capsules

• Explain the formulation of fill materials for soft gelatin capsules

• Explain the filling process for soft gelatin capsules

• Explain packaging of soft gelatin capsules

• Differentiate soft gelatin capsules from hard gelatin capsules

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board and chalk/whiteboard markers

• LCD projector and computer

SESSION OVERVIEW

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing

STEP 2: Definition and Shell Composition (20 minutes)

• Soft gelatin capsules (softgels) are one piece, hermetically sealed, soft

gelatin shells containing a liquid, a suspension or a semisolid

• They are also known as soft elastic capsules (SEC)

• Soft gelatin capsules are available in round, oval, oblong and tube

shapes

• Soft gelatine capsules are mainly used for oral, vaginal and rectal

administration

• Typical soft gels are made up of gelatin, plasticizer, preservatives and

materials that impart the desired appearance (colorants and/or

opacifiers), and sometimes flavours

o Plasticizers

▪ They are materials added to make the softgel shell elastic and

pliable, usually accounting for 20-30%

▪ The most common plasticizer used in softgels is glycerol,

although sorbitol and propylene glycol are used frequently often in

combination with glycerol

▪ The amount and choice of the plasticizer contribute to the

hardness of the final product and may even affect its dissolution

or disintegration characteristics, as well as its physical and

chemical stability

▪ Plasticizers are selected on the basis of their compatibility

with the fill formulation, ease of processing, and the desired

properties of the final soft gel, including hardness, appearance,

handling characteristics and physical stability

▪ One of the most important aspect of soft gel formulation is to

ensure that there is minimum interaction or migration between the

liquid fill matrix and the soft gel shell

▪ The choice of plasticizer type and concentration is important in

ensuring optimum compatibility of the shell with the liquid fill

matrix

o Water

▪ The other essential component of the soft gel shell is water.

Water usually accounts for 30-40 % of the wet gel formulation and

its presence is important to ensure proper processing during gel

preparation and softgel encapsulation

▪ Following encapsulation, excess water is removed from the

softgels through controlled drying

▪ In dry gels the equilibrium water content is typically in the

range 5-8% w/w, which represents the proportion of water that is

bound to the gelatin in the soft gel shell.

▪ This level of water is important for good physical stability,

because in harsh storage conditions softgels will become either too

soft and fuse together, or too hard and brittled

o Colorants/opacifiers

▪ Colorants (soluble dyes, or insoluble pigments or lakes) and

opacifiers are typically used in the wet gel formulation

▪ Colorants can be either synthetic or natural, and are used to

impart the desired shell colour for product identification

▪ An opacifier, usually titanium dioxide may be added to produce an

opaque shell when the fill formulation is a suspension, or to

prevent photo degradation of light-sensitive fill ingredients

▪ Titanium dioxide can either be used alone to produce a white

opaque shell or in combination with pigments to produce a coloured

opaque shell

o Chelating agents

▪ Iron is always present in raw gelatin, excess iron should be

removed

▪ Addition of chelating agent prevents reaction of iron with other

materials e.g. colours

o Preservatives

▪ They are added to prevent from microbial attack e.g. fungi growth

▪ This is important because gelatin is susceptible to microbial

attack

▪ Preservatives include methyl paraben

STEP 3: Advantages and Disadvantages of Soft Gelatin Capsules (10 minutes)

• Advantages of soft gelatin capsules

o Improved bioavailability (drug is presented in a solubilised form)

o Enhanced drug stability

o Liquids can be encapsulated (non aqueous liquids)

o Easier to swallow and taste can improve compliance

o Convenient to carry

o Can be enteric coated for delayed release

o Popular for pharmaceutical, cosmetics and nutritional products

• Disadvantages of soft gelatin capsules

o Require special manufacturing equipment

o Stability concerns with highly water soluble compounds and compounds

susceptible to hydrolysis

o Efflorescent materials cannot be encapsulated

o Deliquescent materials cannot be encapsulated as they will cause

hardening or brittled capsules

o Limited choice of excipients/carriers compatible with gelatin

STEP 4: Formulation of Fill Materials (30 minutes)

• In soft gelatin capsules, the outer shell surrounds a liquid or semi-

solid centre (inner fill)

o Soft gelatin capsules are suitable for liquids and semisolids

• An active ingredient can be incorporated into the outer shell, the inner

fill, or both

• Formulation of the soft gel capsules therefore involves liquid rather

than powder as in hard shell capsules

• Materials are generally formulated to produce the smallest possible

capsule consistent with maximum stability, therapeutic effectiveness and

manufacture efficiency

• Many drug compounds cannot be encapsulated into the soft gelatine

capsules because of their solubility in water and thus their ability to

dissolve the gelatin wall

o E.g. emulsions cannot be filled into these shells because they contain

water which will affect the gelatin

o Aqueous compounds that are minor constituents of a formula or are

combined with a type of carrier (liquid or solid) that reduces their

effect on the shell can be filled into soft gelatin capsules

o The fill content (or inner fills) for the soft gelatin shells are only

non-aqueous materials

o The pH of the liquids filled into soft gelatin capsules can be between

2.5 to 7.5

• There are three primary types of inner fill materials:

o Neat substances

▪ Oily liquids are filled into the capsules

▪ E.g. cod liver oil capsules

o Solution fills

▪ An active solid drug is dissolved in a solvent or carrier

▪ Solvents include oils and polyethylene glycol

o Suspension fills

▪ An active solid drug is dispersed in a carrier

▪ Can accommodate up to 30% solids before viscosity and filling

become a problem

▪ Suspensions can be heated up to 35ºC to decrease viscosity during

the filling process

▪ Suspended solids must be smaller and made homogeneous before

filling to prevent clogging during filling

▪ Suspension is used for solids that are not sufficiently soluble

in liquids or in combinations of liquids

▪ The capsulation of suspensions is the basis for the existence of

a large group of products

▪ The design of suspension type formulations and the choice of the

suspending medium are directed toward producing the smallest size

capsule having maximum production capacity consistent with maximum

physical and ingredient stability and therapeutic efficacy

▪ The formulation of suspensions for capsulation follows the basic

concepts of suspension technology

▪ Formulation techniques, however, can vary depending on the drug

substance, the desired flow characteristics, the physical or

ingredient stability problems, or the biopharmaceutical properties

desired

▪ Examples of suspension fills include drugs suspended in the

following carriers;

▪ Oily soy bean mixtures

o Soybean Oil with beeswax (4-10% w/w) and lecithin (2-4% w/w)

o The lecithin improves material flow, and imparts some

lubrication during filling

o Enough beeswax is added to get a good suspension, but avoid

creating a non-dispersible plug

▪ Polyethylene glycol

o PEG 800 -1000 for semi-solid fills

o PEG 10,000 -100,000 for solid fills

o A mixtures of the above is also employed (Heat up to 35ºC to

make fluid enough for filling)

▪ Optional Ingredients that can be added in the suspension fill:

o Surfactant: sorbitan derivatives such as polysorbate 80 or

lecithin

o For hydrophobic drugs dissolved or dispersed in an oily

matrix, a surfactant of HLB 10 will increase the

dispersibility of the product in aqueous fluids and also may

improve bioavailability

STEP 5: Filling Process for Soft Gelatin Capsules (20 minutes)

• Soft gelatin capsules are usually formed, filled and sealed in one

operation

• Soft gelatin capsules are mainly manufactured by the following methods

(plate process, rotary die process and Globex methods)

o Plate-process Method

▪ A warm sheet of gelatin is placed over a die plate containing

numerous die pockets

▪ Then a vacuum is applied to draw the sheet into the die pockets

▪ Then the pockets (now lined with gelatin) are filled with the

fill liquid or paste

▪ Another gelatin sheet is placed over the filled pockets and

sandwiched under a die press, and the capsules are formed

o Rotary-die Method

▪ This methods uses a rotary die press with two hoppers and two

rotating dies

▪ In this machine the soft gelatin capsules are prepared and filled

immediately with a liquid medicament i.e. formation of the shell

and filling are performed in a single operation

▪ The gelatin liquid mix (for the soft shell) is placed in one

hopper and the liquid medicament is placed in the other hopper

▪ The two rotating dies rotate in opposite directions, and when the

fluid gelatin mixture enters the machine from the hopper, two

continuous gelatin ribbons are formed in half gelatin shells

▪ Measured quantity of the medicament (metered fill) is injected

between the ribbons precisely at the moment that the dies form

pockets of the gelatin ribbons

▪ The two halves of the capsules are sealed together by heat and

pressure of the rotating dies

▪ As the die roll rotate, the convergence of the matching die

pockets seals and cuts out the filled capsules

▪ The capsules are washed with organic solvents and pre-dried

o Globex Method

▪ This method takes advantage of the phenomenon of drop formation

▪ The apparatus used consists of two concentric tubes, through the

inner tube flows the medicament (the fill liquid) and, through the

surrounding outer tube, the gelatin solution (shell forming

solution)

▪ Shell forming solution is pumped through the outer capillary of

the concentric double capillary

▪ The medicament issues from the tube surrounded by gelatin and

forming a spherical drop

▪ This is ensured by allowing the drop to form in cooling bath of

liquid paraffin of about 4°C, in which the gelatin is insoluble

▪ Cooling bath ensures immediate sol-gel transformation, hence

formation of flexible yet firm robust outer film

▪ Soft capsules are collected, washed with organic solvent to

remove residues of cooling liquid, and gently dried at a relative

humidity of 20% in infrared tunnels

▪ The advantage of this method is the production of seamless

capsules which are tamper-evident and free of contamination or

entrapped air

STEP 6: Packaging of Soft Gelatin Capsules (10 minutes)

• Packaging is the science, art and technology of enclosing or protecting

products

• Some of the characteristics of packaging materials include;

➢ Should protect the capsules from environmental conditions

➢ Non-reactive with the product

➢ Not impart taste or odour to the capsules

➢ Nontoxic

➢ Meet applicable tamper resistance requirements

• The capsules are packaged in well closed containers and stored at

temperature not exceeding 30 C

o Glass containers

o Plastic containers

• Capsules are individually protected by enclosing in strip and blister

packaging

o Strip packaging involves hermetically sealing the capsules within the

strip of aluminium or plastic film

▪ A press on the blister forces the capsule through the backing

strip

o Capsules have longer shelf life in unopened glass bottles than in

strip pack and vice versa

STEP 7: Difference between Hard and Soft Gelatin Capsules (15 minutes)

|Hard shell gelatin capsules |Soft shell gelatin capsules |

|Two pieces i.e. short cap and large|One piece, hermetically sealed |

|body | |

|Cylindrical in shape |Round, oval and tube like shapes |

|Powders, pellets, tablets are |Non aqueous liquids and semisolid|

|encapsulated | |

|Gelatin in hard form (less |Gelatin is soft (more |

|plasticizers) |plasticizers) |

|Capsules are sealed after they are |Filling and sealing of the soft |

|filled to ensure that the |gelatin capsules are done in a |

|medicaments may not come out of the |combined operation |

|capsule due to rough handling | |

|Different specific sizes are |No specific size are available |

|available | |

STEP 8: Key Points (5 minutes)

• Soft gelatin capsules (softgels) are one piece, hermetically sealed, soft

gelatin shells containing a liquid, a suspension or a semisolid

• Typical soft gels are made up of gelatin, plasticizer, preservatives and

materials that impart the desired appearance (colorants and/or

opacifiers), and sometimes flavours

• Materials are generally formulated to produce the smallest possible

capsule consistent with maximum stability, therapeutic effectiveness and

manufacture efficiency

• Soft gelatin capsules can be manufactured by plate process, rotary die

process and Globex methods

• The capsules are packaged in well closed containers and stored in a cool

place

STEP 9: Evaluation (5 minutes)

• What is a soft gelatin capsule?

• How do softgels differ from hard gelatin capsules?

• List ingredients used to make the soft gelatin shell

References

Aulton M.E & Kevin M.G, (Eds): (2013) Pharmaceutics: The design and

manufacture of medicines, (4th ed.) Churchill Livingstone.

Hugo and Russell (2011), Pharmaceutical Microbiology (8th ed.), Willey-

Blackwel publications

Gennaro, R. A, et al. (Eds) (1995) Remington: The Science and Practice of

Pharmacy, Volume I & II, (19th ed.): Mack Publishing Company, Easton,

Pennsylvania 18042

Liebsch, B et al. (1988): Tanzania Pharmaceutical Handbook, Dar es Salaam

University Press.

Lund, W. Editor (1994). The Pharmaceutical Codex, Principles and Practice

of Pharmaceutics (12th ed.): The Pharmaceutical Press, London

Polderman, J. (1990) Introduction to Pharmaceutical Production: Novib, The

Hague

Rawlins E.A, Editor: 1977 Bentley’s Textbook of Pharmaceutics, (8th ed).

Baillie're Tindall. London Kamm, G. and Kohler, B. Editors: 1995

Manual for Decentralized Infusion Production, Infusion Unit Project

Tanzania

Schmidt, O. (ed) 2000 Pharmaceutical Quality systems, Interpharm Press,

Colorado.

Shayne C et al (2008), Pharmaceutical Manufacturing Handbook: Production

and processes, John Wiley & Sons

Watson, D. G (1999) Pharmaceutical Analysis: A Textbook for Pharmacy

Students and Pharmaceutical Chemists: Churchill Livingstone,

Edinburgh.

← Previous Topic Next Topic →View all Pharmaceutical Production topics Open Complete Full Notes

PDF / OFFLINE NOTES

Unataka kutumiwa notes hizi kupitia WhatsApp?Kwa notes zilizopangiliwa vizuri kwa kusoma offline au PDF, bonyeza kitufe hapa chini. Ujumbe wenye Level, Semester, Module na Topic utaandaliwa moja kwa moja.TUMIWA NOTES WHATSAPP

WhatsApp: 255620339260