Capsules Flashcards
Common oral solid dosage forms
- Tablets
- Capsules
- Powders/Granules
- Pastilles, lozenges
- Gums
- Oral lyophilisates (i.e. MAXALT MELT (rizatriptan benzoate))
• As before, the key aim is to determine when to use aparticular dosage form
Capsules
Capsule – Capsula – small box
Hard and soft gelatin capsules
Capsules
• Manufacture:
• Manufacture:
– Avoids certain processes (i.e. compaction, possibly granulation, drying – if wet granulation was required)
– Difficult to counterfeit
• Manufacture:
– Specialist filling equipment is normally required
Capsules
• Bioavailability:
• Bioavailability
– May be used to increase oral bioavailability of poorly watersoluble drugs (especially liquid-filled capsules)
– An easy method by which to deliver liquids
• Bioavailability
– Homogeneity of fill
Capsules
• Formulation:
• Formulation:
– A range of formulation types means a range of ways to deliver drugs
• Formulation:
– Physical and chemical stability, particularly for liquid-filled capsules, may be an issue
Hard Gelatin Capsules
- Edible package composed of gelatin (or
occasionally polymers / starch) - Gelatin is derived from animal tissue (type A from the acid treatment of pig skin, type B from an alkaline treatment of demineralised bones – may be used individually or in blends)
- Consist of a cap and body
- Usually filled with powders, but increasingly used for liquid-filled systems
- Capsule has locking device via indentations on outside of body and/or inside of cap
Powder filling of hard gelatin capsules
- Equipment consists of a powder hopper which feeds powder into a reservoir
- Usually dosator used to fill capsules
•dosing tube in which there is a spring loaded piston
•tube plunged into powder bed - powder rises in tube to form ‘plug’
•tube rises out of powder bed, moves over capsule body and plunger moves down, depositing powder in shell - Dose therefore determined by volume of plug in dosator - adjusted by moving position of piston
Powder filling of hard gelatin capsules - industrial scale
• Industrial scale – may be ‘dependent’ or ‘independent’
- Dependent – uses the capsule body directly to measure the powder
- Still used in many countries but slow, can be very dependent on operator skill and uniformity of dosing clearly dependent on powder flow and uniformity of filling
- Independent – most commonly used for large pharma
- ‘Plug’ of material formed from powder which is then transferred to body
- Force used in 10-100N, compared to 10-100kN used for tabletting
- Most common approach is to use a dosator
- The piston may compress powder to form a coherent plug
- The tube rises out of powder bed, moves over capsule body and plunger moves down, depositing powder in shell
- The dose therefore determined by volume of plug in dosator - adjusted by moving position of piston
What is a dosator
– This is a tube containing variable volume chamber at bottom and piston at top
Types of gelatin
• Type A
– From the acid treatment of pig skin, using HCl, H2SO4 or H3PO4 for ca. 1 day, followed by processing, purification, etc.
• Type B
– Alkaline treatment of demineralised bones, by placement in a slurry of calcium hydroxide for 1 – 3 months
– Following this, gelatin is extracted by a series of hot water washes, with water temperature increasing in each subsequent wash
– Solutions form a gel and evaporation of water results in production of solid gelatin
• Replacements / alternatives: HPMC, starch
Difference in types of gelatin
• Type A and Type B gelatin have different properties:
– Different isoelectic points;
– Therefore solubility varies as a function of pH
• Different range of molecular weights
The use of gelatin
• MW – 15,000 – 250,000
• Grade / quality is defined by the bloom strength
– The weight, in grams, required to depress a plunger (of defined 12.7mm diameter) to a defined depth of 4mm within an aged gelatin gel (6.66% w/w) in water.
• Physical / physicochemical properties:
– Non-toxic, widely used in foods
– However, bovine spongiform encephalopathy (BSE) has been an issue (now uses grade 1 – highly unlikely source of BSE, or grade 2 – unlikely but not absolutely excluded)
– Soluble in biological fluids; below 30 degrees gelatin capsules swell but do not dissolve in aqueous solution
– Excellent film-former, so easy to make capsules from it
– Rheological properties enable it to be easily processed, even at high temperatures
– Sol-gel transition means it readily forms a solid when cooled
Composition of hard gelatin capsule shells
Process aids
- Small amount (<0.15% w/v) of sodium lauryl sulphate (SLS) as a wetting agent to ensure that the metal moulds are uniformly covered when dipped into the gelatin solution.
- No longer contain preservatives.
- Moisture levels in the finished capsules are 13.0-16.0% w/v to prevent bacterial growth. (This amount of moisture is strongly bonded to the gelatin molecules, so the water activity / availability is substantially reduced)
Hard Gelatin Capsules
• Filled with:
– Powder (or granules)
– Similar to aspects of tablet manufacture:
• Particle size should be uniform and consistent, to ensure even flow and dosing during filling
• May be granulated – reduces problems of filling with irregular shapes in capsules
– Filling is bench-scale (hospitals, research, clinical trials) or industrial scale (manufacture)
• Filled with:
– Liquid or semisolid formulation (i.e. gel)
• …into which the drug is dispersed or dissolved (i.e. a solution or a suspension)
• Uses a metered volumetric system
• Sensitive to temp
• Prone to leakage, sealing at the join between the capsule cap and the body is vital
Capsule Sizes
Capsules available in 8 sizes with different fill volumes: 5 - 0.13ml 4 - 0.20ml 3 - 0.27ml 2 - 0.37ml 1 - 0.48ml 0 - 0.67ml 00 - 0.95ml 000 - 1.36ml
Size 000 is approx 2cm in height, size 5 about 1cm.
As an example, Size 0 used for 500mg doses of antibiotic
Why use HGCs?
- Industry will generally use tablets if it can
- Capsules used for materials that can not be easily formulated as a tablet due to e.g.
•change polymorphic form on compression
•degrade on compression
•sensitivity to water and not easily dry granulated
•advantages associated with delivering liquids / dispersed systems (i.e. solubility issues)
