Capsules Flashcards
What is a capsule?
A solid dosage form in which the drug substance is enclosed within a hard or soft elastic capsule (usually gelatin)
What are some things that may be added to capsules? To facilitate encapsulation, hydrophobic API powders
Fillers, lubricants, glidants to facilitate encapsulation
Wetting agents for hydrophobic API powders
What are hard shell capsules typically filled with?
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
What might happen to gelatin capsules to cause them to fail stability tests?
The gelatin products might cross-link
How should empty capsule shells be stored?
In airtight containers away from dust, extreme temperatures, and humidity
What are some advantages of capsules for patients?
Tasteless
Elegant
Compact/portable
Ease of administration
What are some advantages of capsules for HCP?
Tasteless
Single/combination dose
Useful for clinical trials
Good bioavailability
What are some disadvantages of capsules?
Cannot use drugs that solubilize gelatin
Not suitable for hygroscopic or deliquescent drugs
Potential for leaking
What are capsule shells made of?
Gelatin, water, colorants, opacifying agents, preservatives, miscellaneous ingredients
What is gelatin (i.e., how is it prepared)?
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
How are capsules made?
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)
What is the advantage of hard-shell capsules over tablets or soft-shell?
They can be hand-filled, allowing prescriber to choose single or combination drugs at precise dose
How is weight assessment performed in quality control of hard capsules?
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
What is a disadvantage of a semi-automatic capsule machine?
There is no assurance of constancy
How is uniformity of dosage units demonstrated?
Content uniformity or weight variation
What is content uniformity? When can we apply content uniformity?
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
What is weight variation?
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%
For hard capsules that are >25mg and >25%, should you use weight variation or content uniformity?
Weight variation
For hard capsules that are
Content uniformity
For soft capsules that are suspensions, emulsions, or gels, should you use weight variation or content uniformity?
Content uniformity
For soft capsules that are solutions, should you use weight variation or content uniformity?
Weight variation
What are the advantages and disadvantages of liquid-filled capsules?
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
What RoA can soft-shell capsules be used for?
Oral, vaginal, rectal; specialty for topical, opthalmic, otic
What are the components in soft-shell formulation? (Shell and capsule filling machine)
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
What are the general advantages of soft gelatin capsules?
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
What are the pharmaceutical advantages of soft gelatin capsules?
Formulations with optimized active substances
Excellent pharmacokinetics/bioavailability
Content uniformity
What is the rupture test for soft gelatin capsules?
Dissolution apparatus with 500mL water and 50rpm paddle speed
Test is passed if capsules rupture within 15 minutes
What is microencapsulation? What is it used for?
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
