SDFs - Capusles

What has the active ingredients sealed in a hard or soft shell made of gelatin or other substances (starch, HPMC)?

Solid dosage forms

Can they be swallowed whole or can be opened to mix powder with foods or drinks?

Yes

What kind of capsules must not be opened?

Enteric-coated & extended-release capsules

What kind of capsules are there?

Hard gelatin + soft gelatin

What makes up hard gelatin capsules?

Gelatin, water, and sugar

What makes hard capsules opaque?

Titanium dioxideis commonly added to hard capsules to provide opacity.

What are the 5 types of hard gelatin capsules?

• Standard

• Snap-fit

• Coni-snap

• Coni-snap Supro

• Polycap

What are the standard hard gelatin capsules?

• Capsule body enters the capsule cap

  • Lacking many features

What are the snap-fit hard gelatin capsules?

• 2 halves are positively joined through locking grooves around the shell walls

• 2 grooves fit into each other and make sure the filled capsule is closed

• Reduces accidental opening of shells

Wha

What is the problem with standard & Snap-fit?

High speed of capsule machine causes splitting (telescoping) &/or denting of the capsule shell with the slightest contact between the 2 rims when they’re joined together W

What are the Coni-snap hard gelatin capsules?

• Locking grooves (~ Snap-fit) make sure the proper closing of the rims of the filled capsules

• Slightly tapered body decreases the capsule rims touching on joining and eliminates splitting and denting

  • Dimples prevent premature opening of capsule

What are Coni-snap Supro?

• Have all features of Coni-snap

• Cap extends so far over body so only the rounded edge of latter is seen

• Opening such a filled capsule is hard because lower surface gives a less gripping surface to pull 2 halves apart

• Increases security of contents and capsule’s integrity (tamper-evident)

What are the Polycap hard gelatin capsules?

• 5-in-1 polypill has moderate levels of 5 different medications in 1, 1-a-day pill intended to decrease heart attacks and strokes

• Has 3 blood pressure medications (diuretic, ACE inhibitor, B-blocker, statin and aspirin)

How do the capsule sizes range?

000 (largest size) → 5 (smallest size)

How do you prepare the formulations?

• General formulation properties for an ideal dosage form

• Ease of filling

• Proper blending of drugs & excipients

• Special care is needed for low-dose drugs

What is useful for low-dose drugs to fill the volume and offers cohesion to the powders?

Diluents

What are some examples of diluents?

• Lactose

• Starch

• Mirocrystalline cellulose

What helps with the breakup and distribution of the capsule contents in the stomach?

Disintegrants

What are some examples of disintegrants?

Pregelantized starch

What helps enhances flow properties?

Lubricants

What are some examples of lubricants?

• Magnesium stearate

• SiO2

• Talc

What helps increase dispersion of powder in GI fluid?

Wetting agents

What are some examples of wetting agents?

Glycerin

What are the types of formulations?

• Powder/granule

• Pellet

• Semi-solid

• Liquid

• Capsule (capsule in capsule)

• Tablet (tablet in capsule)

What performs all the operations needed to prepare capsules at a rate of up to 180,000 caps/hour?

Capsule filling machine

What is capsule sealing?

Kapseals-Tamper-evident capsules, sealed joint (band) between the cap and the body

What is heat welding?

Sealed through a heat welding process that fuses the cap to the body through double wall thickness at this juncture

How are capsules cleaned and polished by a small scale?

Cleaned manually by cloth with NaCl

How are capsules cleaned and polished on a large scale?

Machine (vacuum, NaCl)

What are soft gelatin capsules?

Softgels, containing a liquid or semisolid matrix inside one piece of gelatin shell

What are soft gelatin capsules made out of?

Mainly gelatin, but also glycerin (increasing elasticity) and/or polyhydric alcohol (e.g., sorbitol) to render the gelatin soft or elastic

What kind of liquids are SGCs filled with?

1. Water-immisicible volatile and non-volatile liquids (vegetable & aromatic oils, hydrocarbons, organic acids, ester, alcohols)

2. Water-miscible, nonvolatile liquids (PEG’s non-ionic surfactants aka Tween 20/60/80)

3. Water-miscible and relatively nonvolatile compounds (PEG & isopropyl alcohol)

4. Dissolved or suspended in liquid solvent solids

What are the types of formulations that make up SGCs?

• Solutions

• Suspensions

• Pastes

• Dry powders

• Chewable soft gels

What are 5 advantages of SGCs?

• Improve drug absorption and patient compliance

• Safety of operation from potent cytotoxic drugs

• Oils and low-melting point drugs

• Dose uniformity for low-dose drugs

• Product stability

What is the difference between the shells of the SGCs + HGCs?

SGCs: Plasticized (glycerin, propylene glycol, sorbitol)

HGCs: Not plasticized

What is the difference between the content of SGCs + HGCs?

SGCs: Usually liquids or suspensions (dry solids are possible)

HGCs: Usually dry solids (liquids/semi-solids matrices possible)

What is the difference between the manufacturing process of SGCs + HGCs?

SGCs: Formed/filled in 1 operation

HGCs: Shells made in 1 operation and filled in a separate process

What is the difference between closure of SGCs + HGCs?

SGCs: Hermetically sealed (inherent)

HGCs: Traditional friction-fit; mechanical interlock, banding and liquid sealing possible

What is the difference between the sizes and shapes of SGCs + HGCs?

SGCs: Many

HGCs: Limited

What are the advantages of capsules over SDFs?

• More elegant

• Generally better bioavailability

• Versatile (can carry liquid, semisolid, or solid drugs)

• Easily prepared extemporaneously

• Easily protected from light (opaque shell)

What are the advantages of capsules over LDFs?

• More stable

• Longer shelf-life

• Accurate dosing due to single unit

• Easier transport and storage

• Taste masking is easier

• Easy identification by colored, embossed, or imprinted shell

• Efficient and more productive manufacture, less packing cost

What are the disadvantages of capsules?

• Hygroscopic drugs (KCl) and drugs bound moisture cannot be formulated

• More expensive than a tablet DF

• Soft or brittle hard gelatin shells (humidity)

What is the weight variation test?

• Contents of 10 capsules individually weighed / total weight = average

• Each capsule is cut open

• Contents removed using a suitable solvent

• Solvent evaporated

• Empty dried shells are weighed

• Result must follow USP

What is content uniformity?

• 9/10 tested capsules should have drug strength in the range of 85-115%

• None should fall outside 70-125% of declared potency

What is the disintegration test?

Time for capsule content to disintegrate

What is the dissolution test?

Rate of drug dissolution