Capsules

Question 1

What is a capsule?

Answer 1

A solid dosage form in which the drug substance is enclosed within a hard or soft elastic capsule (usually gelatin)

Question 2

What are some things that may be added to capsules? To facilitate encapsulation, hydrophobic API powders

Answer 2

Fillers, lubricants, glidants to facilitate encapsulation

Wetting agents for hydrophobic API powders

Question 3

What are hard shell capsules typically filled with?

Answer 3

Powders, beads, granules
May coat sugar beads with API to provide extended-release profiles/enteric properties
Larger dose API can be formed into pellets and coated
Semisolids and liquids can also go into hard shell capsules but must be properly sealed

Question 4

What might happen to gelatin capsules to cause them to fail stability tests?

Answer 4

The gelatin products might cross-link

Question 5

How should empty capsule shells be stored?

Answer 5

In airtight containers away from dust, extreme temperatures, and humidity

Question 6

What are some advantages of capsules for patients?

Answer 6

Tasteless
Elegant
Compact/portable
Ease of administration

Question 7

What are some advantages of capsules for HCP?

Answer 7

Tasteless
Single/combination dose
Useful for clinical trials
Good bioavailability

Question 8

What are some disadvantages of capsules?

Answer 8

Cannot use drugs that solubilize gelatin
Not suitable for hygroscopic or deliquescent drugs
Potential for leaking

Question 9

What are capsule shells made of?

Answer 9

Gelatin, water, colorants, opacifying agents, preservatives, miscellaneous ingredients

Question 10

What is gelatin (i.e., how is it prepared)?

Answer 10

Prepared by thermal denaturation of collagen (major structural protein in skin, bone, cartilage, cornea), isolated from animal skin and bones using very dilute acid or base (gelatin A or B) - triple helix is heated, denatures to a gel or sol state
Different IEP (5 and 7)
Large number of glycine, proline, 4-hydroxyproline residues

Question 11

How are capsules made?

Answer 11

Gelatin gravity fed into dipper section then moulded onto stainless steel pin bars dipped in gelatin
Pin bars pass through drying system
Moisture is removed
Capsule halves are individually stripped from pins
Caps and bodies are trimmed
Bodies and caps are joined
QC monitored throughout (size, moisture, thickness, colour)

Question 12

What is the advantage of hard-shell capsules over tablets or soft-shell?

Answer 12

They can be hand-filled, allowing prescriber to choose single or combination drugs at precise dose

Question 13

How is weight assessment performed in quality control of hard capsules?

Answer 13

Weigh 10 capsules from representative sample of each batch and record
Calculate theoretical weight of contents
Determine if there is a deviation of more than 10% in either direction

Question 14

What is a disadvantage of a semi-automatic capsule machine?

Answer 14

There is no assurance of constancy

Question 15

How is uniformity of dosage units demonstrated?

Answer 15

Content uniformity or weight variation

Question 16

What is content uniformity? When can we apply content uniformity?

Answer 16

Assay of individual content of drug substances in number of individual dosage units to determine if individual content is within limits set - applies in all cases

Question 17

What is weight variation?

Answer 17

Products that do not meet 25mg/25% threshold limit should be tested by weight variation (25mg of drug comprising 25% of dosage weight unit) if concentration relative to standard deviation is not more than 2%

Question 18

For hard capsules that are >25mg and >25%, should you use weight variation or content uniformity?

Answer 18

Weight variation

Question 19

For hard capsules that are

Answer 19

Content uniformity

Question 20

For soft capsules that are suspensions, emulsions, or gels, should you use weight variation or content uniformity?

Answer 20

Content uniformity

Question 21

For soft capsules that are solutions, should you use weight variation or content uniformity?

Answer 21

Weight variation

Question 22

What are the advantages and disadvantages of liquid-filled capsules?

Answer 22

Advantages: Increased content uniformity and dissolution, increased homogeneity (therefore more accurate measure), increased dissolution because drug is already in solution or suspended in hydrophilic liquid
Disadvantages: Contact between hard and soft-shell and liquid content is more intimate, may have undesired interaction

Question 23

What RoA can soft-shell capsules be used for?

Answer 23

Oral, vaginal, rectal; specialty for topical, opthalmic, otic

Question 24

What are the components in soft-shell formulation? (Shell and capsule filling machine)

Answer 24

Shell (similar to HGC): Gelatin, plasticizer (e.g., glycerin), water, preservatives, colourants, opacifying agents, flavouring agents
Capsule filling machine: Single liquid, liquid blend, suspension, semisolids, dry powders

Question 25

What are the general advantages of soft gelatin capsules?

Answer 25

Large variety of forms, sizes, colours
Protection of sensitive active substances and auxiliaries
Can encapsulate liquids and solution of diverse polarity and suspensions
Controllable rates of dissolution
High marketing potential
High acceptance by industrial customers and patients

Question 26

What are the pharmaceutical advantages of soft gelatin capsules?

Answer 26

Formulations with optimized active substances
Excellent pharmacokinetics/bioavailability
Content uniformity

Question 27

What is the rupture test for soft gelatin capsules?

Answer 27

Dissolution apparatus with 500mL water and 50rpm paddle speed
Test is passed if capsules rupture within 15 minutes

Question 28

What is microencapsulation? What is it used for?

Answer 28

Technique by which thin coatings are applied to small particles
Uses: mask bitter tasting drugs, sustained/prolonged release, separate incompatible drugs, protect from oxygen and moisture, modify physical and chemical properties