Solid Dosage Forms (Capsules)

Capules

Solid dosage forms containing active substances and inactive substances inside small shells of gelatine or gelatin substitutes

Types of capsules

Hard and soft

Advantages of hard capsules

Mask the taste/odor of unpleasant drugs and can be easily administered

Are easier formulation than tablets

Are goof for poorly compressible material

Can be produced on very small scale, unlike tablets

Are economical and attractive in appearance

Are easy to swallow with some water

Require less excipients than tablets

Are easy to handle and carry

Can be opacified or colored to protect from light

Disadvantages of capsules

Moisture sensitive and become sticky in high humidity and brittle in very low humidity

Might require a desiccant inside the package if intended to be sold in humid areas

Large scale manufacturing requires expensive machinery

What are hard capsules used for

Commercial medicated capsules

Clinical supplies and placebos

Compounded capsules

How are most capsules intended to be used

Most capsules are intended to be swallowed. With a pharmacist approval, some capsules are opened to get the contents especially for patients who are not able to swallow

Characteristics of Hard Gelatin Capsules

The shells are made of a mixture of gelatin, water, and some additives.

They are clear, colorless, and tasteless however they can be colored and made opaque with titanium dioxide.

Most capsules contain combinations of colorants and opaquants. Caps and bodies can have different colors.

Which dyes are preferred

FD and C

It is usually used more often in food and safer to use than D and C

Gelatin

Is a protein obtained by partial hydrolysis of collagen which we can get from skin, connective tissues, and bones of animals. Sourced from cows, pig, and fish.

Gelatine Alternatives

HPMC (Hydroxymethyl Cellulose)

Starch - modified starch (veggies capsules)

These provide better protection from humidity

Manufacturing of Hard Shell Capsules

Manufactured in two sections. The capsule body and shorter caps, overlap when joined. It is important to control the thickness of gelatin walls so that the capsule’s body and cap fit snugly to prevent disengagement. Some capsules are made with tapering ends. Another design for capsules is called Coni-snap where there are grooves in the walls.

Hard Capsule Sizes

Empty capsules are manufactured in various length, diameters, and capacities. For human use the sizes range from 000 to 5. The larger the number the smaller the capsule.

Goal of formulation of a hard capsule

Elegance

Accurate dosage form

Good Bioavailability

Acceptable stability

Ease of filling

Components of a Hard Capsule

Capsule Shells, active, excipients

Development of HC shell

Choose size

Choose color

Choose composition (gelatin, HPMC)

How much powder can a HC contain

65mg to 1g

How is capsule size determined

By trail

Are gelatin capsules suitable for aqueous liquids

No

Formulation of Active in HC

Preformulation studies should be done to determine the micrometric, stability, compatibility, and physiochemical properties of the active powder. Dose determination.

Formulation of Excipients in HC

Need to consider saftey, compatibility, cost and availability.

Examples of Diluents

Lactose, MCC, maltodextrin

Examples of glidants and lubricants

Talc, Mg stearate, fumed silica

Examples of wetting agents

Sodium lauryl Sulfate

Examples of disintegrants

Starch, sodium starch glycolate, crosspovidone

Purpose of Diluents

Adjust capsule weight

Purpose of glidants/lubricants

To enhance flow, speed, and uniformity of fill

Purpose of wetting agents

For poorly soluble drugs to enhance dissolution

Purpose of disintegrants

To help breaking up the capsule and distributing the capsules contents in the GI tract

What can capsules be filled with

Loose powders

Granules

Pellets

Tablets

Smaller capsules

Oils

Steps to filling a hard capsule in a lab

Orient the shell

Open the capsule

Fill the body

Re-cap and close

Sealing (optional)

cleaning and polishing filled capsules

Steps to filling a hard capsule on an industrial scale

Weigh ingredients

Sieving

Mixing (granulation or palletization is optional)

testing for homogeneity

filling powder into capsule

quality control tests

packaging

Capsule Filling: lab

Bench Scale Filling

Used for lab scale

50-300 capsules

For special development

Capsule filling: industry

Industrial scale filler

semi to fully automates

5000-200,000 capsules per hour

Soft gel capsules

Are solid capsules surrounding a liquid or semi-solid center. An active ingredient can be incorporated into the outer shell, the inner fill, or both. Are one-piece forms that encase a predetermined dose of liquid, semi liquid, or solid fill. Are filled and hermetically sealed in a single operation.

Composition of soft gel capsules

They are made of gelatin and glycerin or sorbitol.

Contain more moisture than hard gelatin so preservatives may be added to prevent microbial growth.

Hermetically seal liquids, suspension, pastes, dry powders and even prefabricated tablets.

Elegant and easy to swallow

Examples of preservatives or soft gel capsule

Methylparaben and Propylparaben

Advantages of soft gel capsules

Improved bioavailability

Enhanced drug stability

Superior patient compliance

Product differentiation by color, size, and shape

Portability and easy to swallow

Better tamper evidence

Cloaking bad taste

Uniformity and precision dosage

Disadvantages of Soft Gel Capsules

Water soluble materials are difficult to incorporate

Highly moisture sensitive

Dose adjustment is not an option

High equipment cost

High running cost

Steps of manufacturing soft gel capsules

Prepare gelatin-based ribbons (include color/flavor)

Prepare filled liquid

Encapsulate and hermetically seal te fill with the ribbon

Cool to prevent sticking

Dry

Package

What does the size and shape of a SC depend on

The molds (dies) used

Anatomy of a SC

Shell and Fill

Fill contains suspending agents

Quality Control Requirments

Need to identify how much active, how much drug is released from the capsule in a specific time (dissolution), uniformity of dose, loss on drying, and how much active is there in the dosage form (assay)