DEVELOPING THE

FORMULATION
18 LACAP, DIXIE MAE N.
What is
the GOAL?

To prepare a capsule with:
> Accurate dosage
> Good bioavailability
> Ease of filling &
production stability
> Elegance



DRY FORMULATIONS
- active and inactive components must be blended
thoroughly to ensure a uniform powder mix for the fill.

LOW-DOSE DRUGS
Care in blending
Lack of homogeneity in blending may result in
significant therapeutic consequences.
PRE-FORMULATION STUDIES
To determine:
if all the formulations bulk powders may be
effectively blended together.
require reduction of particle size
any other processing to achieve homogeneity
DILUENT/FILLER

added to the
formulation to
produce the proper
capsule fill
volume
provides bulk and
cohesion to the
powder
beneficial in
transferring
powder blends into
capsule shells
DISINTEGRANTS
> Assist the breakup and distribution of the
capsule

s content in the stomach

HOW TO ACHIEVE UNIFORM DRUG
DISTRIBUTION?
*Density and particle of the drug and nondrug components
must be similar

Particle size
may be reduced
by:
MILLING
MICRONIZATION
MILLED POWDER
Milling process
particles ranging from
50 to 1000 micrometer
blended effectively for
uniform distribution
throughout a powder mix
ONLY IF the DRUG DOSAGE
is 10 mg or GREATER
MICRONIZED
POWDER
Micronization Process
DRUG DOSAGE:less than 10 mg
PARTICLE SIZE:1-20 um(mcm)
for lower dose or smaller
particles
HIGH SPEED AUTOMATED
EQUIPMENT
LUBRICANT/GLIDANT
enhances flow properties of powder
mix
aids in high-speed automated
equipment (industrial scale
production)
Magnesium Stearate
(lubricant) for it

s waterproofing
characteristics
can

t be penetrated by the
gastrointestinal fluids
delays drug dissolution & absorption
useful for modied release capsule
SODIUM LAURYL
SULFATE
surface active
agent
facilitates
wetting by the GI
fluids
is added to aid
drug dissolution
and absorption
delay
DISINTEGRATION
AGENTS
facilitates breakup and
distribution of the
capsule

s content
aids GI fluids to
displace the air around
the powder for the
penetration to occur
and drug dispersion and
dissolution to start
microcrystalline cellulose
Why do we INSERT CAPSULES/
TABLETS inside capsules?
to separate chemically
incompatible agents
to add pre-measured
amounts of potent drug
subs.
rather than weighing a potent
drug
COATED PELLETS
(industrial scale)
designed for
modified release
drug delivery
commonly placed in
capsule shells
DICLOMAX
diclofenac
SLOW RELEASE
GELATIN CAPSULES
unsustainable for
aqueous liquids
water softens
gelatin, causing
leakage
GELATIN CAPSULES
FIXED OR VOLATILE OIL
do not interfere with gelatin shell
stability
LOCKING GELATIN CAPSULES/ Capsule
sealed with a THIN COAT OF GELATIN
WET MASS/PASTE
fixed/volatile oil with INERT POWDER
placed in caps. in usual manner
ex POLYETHER
EUTECTIC MIXTURES
mixtures of agents that have a propensity
to liquefy when admixed
mixed with a DILUENT/ADSORBENT to
separate interacting agent & to absorb
any liquefied material that may form
LARGE SCALE CAPSULE
PRODUCTION
liquids are placed in SOFT GELATIN
CAPSULES that are sealed during filling &
manufacturing
IND. VS COMMUN.
slight loss in fill material during
preparation & capsule filling will not
materially affect an industrial sized
batch
slight loss of powder could result in an
inadequate quantity to fill the last
capsule
CP can calculate in excess of 1 or two capsules more than what is
required to ll the capsule EXCEPT when dealing with capsules
containing controlled subs!

amount of drug used & called for must STRICTLY COINCIDE
SELECTING THE
CAPSULE SIZE
18 LACAP, DIXIE MAE N.
DURING PRODUCT
DEVELOPMENT
FORMULATION
REQUIREMENTS
dose of the active ingredient
density and compaction
characteristics
Diluents are added when dose of the
drug is inadequate to fill the volume
of the capsule body
GUIDE IN SELECTING
CAPSULE SIZE
density & compaction characteristics
of a capsule

s active & inactive

components
comparison to other similar materials
prior experiences
HARD GELATIN
CAPSULES
encapsulates 65 mg- 1g
SMALLEST CAPSULE(#5)
65 mg or more
SELECTING THE
CAPSULE SIZE
(extemporaneous) best capsule size
determined by TRIAL
SMALLEST PROPERLY FILLED capsule
body filled with the drug mixture,
not the cap
Easy Method to Select
the Proper Capsule Size
weigh ing. for the REQUIRED # OF
CAPSULES
place powder in GRADUATED
CYLINDER(take note of volume)
divide volume by the # of capsules
compare the vol with the approx. on
the table and select the caps. size
that will accommodate the powder
if caps is to big

caps size(ml) x #caps = FINAL
VOLUME

then just add diluent to attain
the nal volume
TETRACYCLINE CAPSULES
ACTIVE ING: Tetracycline
HCl (250 mg)
FILLER: Lactose
LUBRICANT: Magnesium
Stearate
CAPS COLORANT: FD&C
YELLOW#6
CAPS OPAQUANT:Titanium
dioxide
FILLING HARD CAPSULE
SHELLS
18 LACAP, DIXIE MAE N.
PUNCH METHOD
amount of powder packed into the
capsule depends on the degree of
compression
should punch each capsule in the same
manner and weigh the product after
capping
NONPOTENT drug - 1st filled capsule
is weighed
POTENT drug - EACH CAPS is weighed
such weighing protects
against uneven lling of
capsules and premature
exhaustion or underuse of
powder
PUNCH METHOD
HAND-OPERATED FILLING
MACHINE
24-300 caps per machine

200-2000 caps per hour
MACHINE DEVELOPED
FOR INDUSTRIAL USE
automatically separate
th caps from the empty
capsules
fills the bodies
scrapes off the excess
powder
replace the caps
seals the capsiles
cleans the outside caps
165000 caps per hour

ACCURACY OF DRUG DOSGE IS
VERIFIED THROUGH

AYTOMATED IN PROCESS
SAMPLING & ANALYSIS

CAPSULE SEALING
18 LACAP, DIXIE MAE N.
TAMPER EVIDENT CAPSULES
KAPSEALS, PARKE-
DAVIS
seals with a colored
band of gelatin
if removed, the band
cannot be restored
without expert
releasing with gelatin
HEAT-WELDING
PROCESS
fuses cap to the
body through the
double wall
thickness at their
juncture
distinctive ring
around the capsule
where heat welded
TAMPER EVIDENT CAPSULES
THERMAL COUPLING

uses a liquid
wetting agent that
lowers the melting
point in the contact
areas of the cap and
body, and then
thermally bonds the
two parts using low
temp (40C-45C)
CAPSULE SEALING
INDUSTRIAL CAPSULE SEALING MACHINES
60000 to 150000 gelatin banded, heat
welded or thermally coupled capsules
PER HOUR
EXTEMPORANEOUSLY
seal by lightly coating the inner
surface of the cap with a warm
gelatin soln then immediately pour to
placement on the filled capsule body.
CLEANING AND
POLISHING CAPSULES
18 LACAP, DIXIE MAE N.
CLEANING & POLISHING CAPSULE
MACHINE