FORMULATION OF CAPSULES SPECIAL TECHNIQUES FOR HGC

CHAPTER 7 IMPRINTING
 Solid dosage forms in which one or more medicinal and inert  convenient method for production identification, best
ingredients are enclosed within a small shell or container performed on empty capsules using edible inks
generally prepared from a suitable form of gelatin SEALING OR BANDING
ADVANTAGES OF CAPSULE AS DOSAGE FORM:  use of hot gelatin
 Portable  provides distinct appearance
 easy to use  prevents filled caps from unjoining
 provides a smooth, slippery, easily swallowed  permits color coding
 provides tasteless shell for drugs  provides tamper-proof feature
DISADVANTAGES OF CAPSULE AS DOSAGE FORM: LOCKING CAPSULES
 not to use for extremely soluble salts (KCl, KBr, etc.)  deliberate modification is made on one or more of the
 not to use for highly efflorescent or deliquescent materials normal contours of the capsule, so that the body is more
 Efflorescent materials – cause capsule to soften tightly held to the cap, after closing.
 Deliquescent materials – cause capsule shell to excessive SPECIAL PURPOSE CAPSULE
brittleness  capsules to which special treatment has been given to delay
HARD GELATIN CAPSULE (HGC) solubility (SR. FR)
 “Dry filled capsule” GENERAL CONSIDERATIONS FOR HGC
 They are made up of gelatin, sugar and water  Active Ingredient
 Fillers
 May contain 0.15% sulfur dioxide
 Antifrictional Agents
MATERIALS IN THE PRODUCTION OF HGC  Disintegrants
1. GELATIN BLENDS  Surfactants
 heterogenous product derived by irreversible hydrolytic  Hydrophilization
extraction of treated animal collagen (animal bones, pork ACTIVE INGREDIENT
skin)
A. Pork skin  Amount and type influence capsule size and the
- “Type A Gelatin”  nature and amount of excipients to be used
- derived from acid-treated precursor  Ideally, dose > 10 mg
B. Calf bone gelatin  For low water solubility
- “Type B gelatin” - Micronize to increase dissolution rate
- derived from alkali-treated precursor
- Reduce particle size to increase surface area for dissolution
2. CERTIFIED DYES
3. OPACIFYINQ AGENTS FILLERS
- Titanium dioxide  Most common capsule diluents: starch, lactose, dicalcium
4. PLASTICIZERS phosphate
5. PRESERVATIVES ANTIFRICTIONAL AGENTS
METHODS OF PRODUCTION OF HGC
 GLIDANTS: <1% (0.25%- 0.5%)
PIN METHOD

Colloidal silicas, cornstarch, talc, magnesium stearate
 completely automatic machine most commonly used for
capsule production consists of mechanisms for automatically: 
Enhances fluidity by
- Reducing roughness by filling surface irregularities
Dipping  Spinning  Drying  Trimming  Stripping 
- Reducing attractive forces by physically separating the
Joining the capsules
host particles
PROPER STORAGE OF HGC
- Modifying electric charges
 Temperature should not exceed 100ºF
- Acting as moisture scavengers
 Open storage under either high or low humidity should be
- Serving as ball bearings between host particles
minimized
 LUBRICANTS
 tight-well-closed container
 Magnesium stearate, stearic acid
 Empty HGC contain 12-15% moisture
 Eases the ejection of plugs
 below 10% moisture content, the capsule become brittle
 Reduce filming on pistons and adhesion of powder to
and may shrink
metal surfaces
FINISHING METHODS FOR FILLED HGC
 Reduce friction between sliding surfaces in contact
CLOTH POLISHING
 bulk filled capsules are rubbed with a cloth (may or may not  with powder conc of hydrophobic lubricants; retards drug
release
be impregnated with oil); imparts an improved gloss to the
capsules, as it removes resistant materials SURFACTANTS
 hand operation procedure  0.1%- 0.5 % SLS or Na Docusate
BRUSHING  Increases wetting of the powder mass
 capsules are fed under rotating soft brushes, which may  Enhances drug dissolution
remove dust from the capsule shells; vacuum dust removal  “waterproofing” effect of hydrophobic lubricants may be
system must accompany this operation offset by the use of surfactants
 Limitations: may cause deformation and scratches HYDROPHILIZATION
 Process of spreading a solution of hydrophilic polymer onto
the drug in a high-shear mixer, the resultant mixture dried
and screened
 Improves wettability of poorly soluble drug
LIQUID FILLED HGC
 Liquid material must not dissolve, alter or adversely affect
the integrity of the shell
 Fill material should be pumpable
 Formulation strategies for Liquid filled- Hard gelatin capsules
 Thixotropic formulations
- Colloidal silicas
 Thermal setting formulation
- PEG 20,000 or 6% @ of beeswax and/or fumed silicon
dioxide
 Mixed thermal/ thixotropic systems
 More lipophilic the contents, slower release rate
WHICH CAPSULE SIZE TO USE?
Estimation of Fill Weights:
 For Powders: multiply the body volume (capacity) by its
tapped density
 For Liquids: multiply the specific gravity by the body
volume (capacity) x 0.8
SOFT GELATIN CAPSULE (SGC)
 “Soft elastic capsule”
Pharmaceutical applications:
 as an oral dosage form for ethical or proprietary products for
human or veterinary use
 as a suppository for rectal or vaginal use
 as a specialty package in tube form, for human and veterinary
single dose application of topical or ophthalmic preparations,
rectal ointments, nasal or otic drops
 in the cosmetic industry, as a specialty package for breath
fresheners, bath oils, shampoos, suntan lotions, perfume and
some skin creams
 Soft gelatin capsule filling
 Capsules containing drug as major component
- Oils or drugs highly soluble in oils
 Sealing temperature of gel films is 37°C to 40°C
 Limitations:
Water ( greater then 5% of contents)
Emulsions that give off water
Low MW alcohols( Ethyl alcohol and aldehydes)
MATERIALS IN THE PRODUCTION OF SGC
1. Gelatin
2. Plasticizers
3. Water
4. Optional components such as preservatives, colorants,
opacifying agents, flavoring agents
METHODS OF PRODUCTION OF SGC
 Plate Process
 Rotary Die Process
 Reciprocating Die Process
PLATE PROCESS
 a set of molds is used, a warm sheet of gelatin is laid over the
lower plate and the liquid is poured on it. A second sheet of
gelatin is put in place, this is followed by the top plate of the
mold and pressed under pressure.
ROTARY DIE PROCESS
 Liquid gelatin flowing from n overhead tank is formed into
two continuous ribbons by the rotary die machine and
brought together between twin rotating dies.
 At the same time, metered fill material is injected between
the ribbons precisely at the moment that the dies form
pockets of the gelatin ribbons.
 These pockets of fill-containing gelatin are sealed by pressure
and heat and then severed from the ribbon.
RECIPROCATING DIE PROCESS
 Similar to rotary die process in that ribbons of gelatin are
formed and used to encapsulate the fill, but it differs in the
actual encapsulating process
 The gelatin ribbons are fed between a set of vertical dies that
continually open and close to form rows of pockets in the
gelatin ribbon.
 These pockets are filled with medication and are sealed,
shaped and cut out of the film.
 As they are being cut, they fall into refrigerated tanks which
prevent the capsules from adhering to one another
SPECIAL TECHNIQUES FOR SGC PRODUCTION
MICROENCAPSULATION
 process of application of relatively thin coatings to small
particles of solids or droplets of liquid and dispersions
 this involves the coating of particles ranging dimensionally
from several tenths of a micron to 5000 microns in size
GENERAL CONSIDERATIONS FOR SOFT SHELL CAPSULES
 Materials are generally formulated to produce the smallest
possible capsule consistent with maximum stability,
therapeutic effectiveness, and manufacture efficiency.
 2.5 >pH> 7.5
– More acid pH – hydrolyzes gelatin
– More alkaline – tanning the gelatin
 All liquids for filling must flow by gravity at a temperature of
35°C or less
 Categories of vehicles
 Water-immiscible volatile/nonvolatile
- Vegetable oils, aromatic and aliphatic HC
 Water-miscible nonvolatile
- Low MW polyethylene glycol
 Suspension
 Micronize all materials
 Suspending agents:
 For oily bases:
- 5% beeswax, paraffin wax
- 1-6% animal stearates
 For non-oily bases:
- 1-5% PEG 4000 and PEG 6000
- 10% solid ninionics
- 10% solid glycol esters