Chapter 7: apsules
gamma ray-emitting
Solid dosage forms
Conveniently carried
Readily identified = safe & effective
medication use
Easily taken; tasteless
Lower manufacture cost; less
breakage
More stable; longer shelf life
Enteric-coated tablets pass through
stomach for drug release & intestine
absorption
Extended release prolonged release
of medication
Sublingual / buccal dissolve under
tongue or mouth
Overview of Capsules
Solid dosage forms in w/c medicinal
agents &/or inert substances are
enclosed in a small shell of gelatin
(hard / soft)
Two pieces: cap & body hard-shell
One piece soft-shell
Hard-Gelatin Capsules
Used in most commercial medicated
capsules
Employed in clinical drug trials
Extemporaneous compounding
Made of gelatin, sugar, water
Colorants: FD&C; D&C dyes
Opaquants: titanium dioxide
Gelatin
o obtained by partial hydrolysis of
collagen obtained from skin,
white connective tissue, and
bones of animals
o stable in air when dry
o subject to microbial
decomposition when moist
o 13-16% moisture
o High humidity absorb moisture
distorted & lose rigid shape;
affect in vitro capsule dissolution
o extreme dryness brittle &
crumble
o Desiccant dried silica gel, clay,
and activated charcoal; protect
from moisture absorption
o Soluble in hot / warm water
o Protein; digested by proteolytic
enzymes and absorbed
Methods to track passage of
capsules:
o Gamma Scintigraphy
- noninvasive procedure; use of
radiotracer
- small quantity of material
- pharmacoscintographic
evaluation info on transit &
drug release pattern
- determine correlation bet. in
vitro & in vivo bioavailability
for immediate-release
- assess integrity & transit time
of enteric-coated
- drug & dosage form
evaluation in new product
devlpt.
o Heidelberg capsule
- pH-sensitive nondigestible
radiotelemetric devide
- no. 0 capsule used as
nonradioactive means to
measure gastric pH,
emptying time & residence
time
absorption from GI tract depend on:
o solubility of drug substance
o type of product formulation
o GI contents
o Intersubject differences
Manufacture of Hard Gelatin Capsules
Produced industrially
Mechanical dipping of pins / pegs of
desired shape in a temp-controlled
reservoir of melted gelatin mixture
Pegs ( manganese bronze ) affixed to
plates ( hold up to 500 pegs )
Each plate lowered to gelatin bath;
Pegs submerged to desired depth;
proper thickness & length
Dried by temp & humidity controlled
air
Mechanically trimmed & removed
from pegs
Continuous dipping, drying,
removing, joining of capsules
Taper the end of body, cap-making
peg rounded ( Pulvules, Eli Lilly )
Both ends of cap & body tapered
( Spansule, SmithKline Beecham )
Innovation: Snap-fit & Coni-snap
Orginal Snap-Fit
o Enables 2 halves of shells to
be joined together through
locking grooves in shell walls
o Problem: splitting
(telescoping) & denting of
capsule shell occur w/ the
slightest contact bet. 2 rims
 Coni-Snap
o The prob. Led to the devlpt.
Where rim of capsule is not
straight but slightly tapered
o Avoid telescoping; prevent
premature opening; lock 2
parts together
Coni-Snap Supro
o Upper part extends over the
lower part that only the
rounded edge of body is
visible
o Increases security of contents
& capsule integrity
o Opening is difficult lower
surface area = less gripping
surface
Capsule Sizes
Size 000 largest; size 5 smallest
Large capsules for veterinary use
Wide number of options for
prescription compounding
Preparation of Filled Hard Gelatin
Capsules
Develop & prepare formulation;
Select capsule size
Fill capsule shells
Capsule sealing ( optional )
Clean & polish the capsule
Developing the Formulation &
Selecting Capsule Size
Goal:
o Capsule w/ accurate dosage
o Good bioavailability, elegance
o Ease of filling, production, stability
Blending care is important for low-
dose drugs
Preformulation studies to determine
whether powders are blended to
achieve homogeneity
Diluent / filler to produce proper
capsule fill volume ( Lactose;
microcrystalline cellulose;
starch; Confectioners Sugar )
o Often provide cohesion
Disintegrants to assist breakup &
distribution of capsules contents in
stomach ( starch; croscarmellose;
sodium starch glycolate )
To achieve uniform drug distribution
= density & particle size of drug &
nondrug are similar
Milling to reduce particle size by
50-1000mm
Micronization for drugs of lower
dose / smaller particles are required
Preparing capsules on industrial
scale
o High-speed automated equipment
- Powder mix must be free-
flowing to allow steady passage
from hopper to capsule shells
o Lubricant / Glidant enhance flow
properties ( Silicon dioxide; Mg
stearate; Ca stearate; stearic
acid; Talc )
o When Mg Stearate (water insol.) is
used waterproofing charac. can
retard penetration; & delay drug
absorption
o Surface-active agent to facilitate
wetting by GI fluids to overcome
mg stearate problem ( Sodium
Lauryl Sulfate )
Inserting tablets or small capsules
separate chemically incompatible
agents
Gelatin capsules unsuitable for
aqueous liquids -> water soften
gelatin & distorts capsule
o Fixed / Volatile oil may be
sealed w/ thin coating to
ensure retention of liquid;
dont interfere w/ stability of
shell
o Inert powder to make wet
mass / paste; then placed in
capsule