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Pharmmanuf. Formulation of Capsules
Pharmmanuf. Formulation of Capsules
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 Plate Process
the drug in a high-shear mixer, the resultant mixture dried Rotary Die Process
and screened Reciprocating Die Process
Improves wettability of poorly soluble drug PLATE PROCESS
LIQUID FILLED HGC a set of molds is used, a warm sheet of gelatin is laid over the
Liquid material must not dissolve, alter or adversely affect lower plate and the liquid is poured on it. A second sheet of
the integrity of the shell gelatin is put in place, this is followed by the top plate of the
Fill material should be pumpable mold and pressed under pressure.
Formulation strategies for Liquid filled- Hard gelatin capsules ROTARY DIE PROCESS
Thixotropic formulations Liquid gelatin flowing from n overhead tank is formed into
- Colloidal silicas two continuous ribbons by the rotary die machine and
Thermal setting formulation brought together between twin rotating dies.
- PEG 20,000 or 6% @ of beeswax and/or fumed silicon At the same time, metered fill material is injected between
dioxide the ribbons precisely at the moment that the dies form
Mixed thermal/ thixotropic systems pockets of the gelatin ribbons.
More lipophilic the contents, slower release rate These pockets of fill-containing gelatin are sealed by pressure
WHICH CAPSULE SIZE TO USE? 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.
Estimation of Fill Weights: As they are being cut, they fall into refrigerated tanks which
For Powders: multiply the body volume (capacity) by its prevent the capsules from adhering to one another
tapped density SPECIAL TECHNIQUES FOR SGC PRODUCTION
For Liquids: multiply the specific gravity by the body MICROENCAPSULATION
volume (capacity) x 0.8 process of application of relatively thin coatings to small
SOFT GELATIN CAPSULE (SGC) particles of solids or droplets of liquid and dispersions
“Soft elastic capsule” this involves the coating of particles ranging dimensionally
Pharmaceutical applications: from several tenths of a micron to 5000 microns in size
as an oral dosage form for ethical or proprietary products for GENERAL CONSIDERATIONS FOR SOFT SHELL CAPSULES
human or veterinary use Materials are generally formulated to produce the smallest
as a suppository for rectal or vaginal use possible capsule consistent with maximum stability,
as a specialty package in tube form, for human and veterinary therapeutic effectiveness, and manufacture efficiency.
single dose application of topical or ophthalmic preparations, 2.5 >pH> 7.5
rectal ointments, nasal or otic drops – More acid pH – hydrolyzes gelatin
in the cosmetic industry, as a specialty package for breath – More alkaline – tanning the gelatin
fresheners, bath oils, shampoos, suntan lotions, perfume and All liquids for filling must flow by gravity at a temperature of
some skin creams 35°C or less
Soft gelatin capsule filling Categories of vehicles
Capsules containing drug as major component Water-immiscible volatile/nonvolatile
- Oils or drugs highly soluble in oils - Vegetable oils, aromatic and aliphatic HC
Sealing temperature of gel films is 37°C to 40°C Water-miscible nonvolatile
Limitations: - Low MW polyethylene glycol
Water ( greater then 5% of contents) Suspension
Emulsions that give off water Micronize all materials
Low MW alcohols( Ethyl alcohol and aldehydes) Suspending agents:
MATERIALS IN THE PRODUCTION OF SGC For oily bases:
1. Gelatin - 5% beeswax, paraffin wax
2. Plasticizers - 1-6% animal stearates
3. Water For non-oily bases:
4. Optional components such as preservatives, colorants, - 1-5% PEG 4000 and PEG 6000
opacifying agents, flavoring agents - 10% solid ninionics
- 10% solid glycol esters
METHODS OF PRODUCTION OF SGC