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Dosage Form
Pharmaceutical Dosage
Chewable tablet
Chapter 7: Capsules Instant dissolving tablet
Oral liquid
Capsules and Tablets Oral or nasal inhalation solution
Suppository
Preferred when administered orally by adults: conveniently Injection
carried, readily identified, easily taken
Variety of dosage strengths, providing: Characteristics
Flexibility to the prescriber
Accurate individualized dosage for the patient May be swallowed whole by patient
May be inserted into the rectum for drug release and
Pharmaceutical Standpoints
absorption from site
The content may be removed from the gelatin shell and
Solid dosage forms:
employed as pre measured medicinal powder, the capsule
Manufactured efficiently and productively
shell being use to contain a dose of the medicinal
Packaged and shipped at lower cost and with less
substance.
breakage
Ex: Theo-dur Sprinkle
More stable
Elegance
Have longer shelf life than liquids
Ease of use
Disadvantages of Tablets and Capsules Portability
Tasteless shell to mask the unpleasant taste/ odor
Swallowing Permits physician to prescribe the exact medication needed
Formulation difficulties buy the patient
Some have poor bioavailability or poor water solubility Conveniently carried
Some have irritant effect on the GIT when taken orally Readily identified
Easily taken
Key Features of a Good Tablet or Capsule Tasteless when swallowed
Commonly embossed or imprinted on their surface the
Stability of the active drug manufacturer’s name and product code readily identified
Accurate dose Available in variety of dosage strength
Uniformity (weight, amount of active ingredient, coating Provide flexibility to the prescriber and accurate
thickness, etc) individualized dosage for the patient
Consistent performance (manufacturing parameters, Packaged and shipped by manufacturers at lower cost, less
pharmacokinetics) breakage than liquid forms
Appropriate disintegration and dissolution More stable and longer shelf life
Can withstand packaging, shipping, handling without
breakage Hard Gelatin Capsules
Masking of taste and odor
Pharmaceutically elegant Also referred to as “DFC” Dry Filled Capsule,
Production economically sound manufactured into two sections, the capsule body and a
shorter cap
Overview of Capsules Manufacture most of the commercially available medicated
capsules
Capsules Employed in clinical drug trials
Medicinal agents and/or inert substances For extemporaneous compounding of
enclosed in a small shell of gelatin prescriptions
Swallowed wholly Contains 13% to 16% moisture
Open capsule or crushed tablets Manufactured form:
Mixed with food or drink (children or patients Gelatin
who are unable to swallow solid dosage forms) Titanium dioxide (opacifying agent)
0.15% SO2 (prevents decomposition of gelatin)
Solid Dosage Forms that must be Left Intact Colorants
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Made opaque by adding agents like titanium oxide Magnesium stearate
Stearic acid or talc (about 0.25-1%)
Gelatin Surface active agent (surfactant)
To facilitate wetting by GI fluids
Obtained by partial hydrolysis of collagen from the skin, Sodium lauryl sulfate
white connective tissue and bones of animals
Properties: Fixed or Volatile Oils
Stable in air (dry)
Subject to microbial decompositions when Do not interfere with stability of the gelatin shells
moistened
Insoluble in cold water, softens through Eutectic Mixture of Drugs
absorption of up to 10 times its weight of water
Soluble in hot water and in warm gastric fluid Mixtures of agents that have a propensity to liquefy when
A protein, digested by proteolytic enzymes and admixed
absorbed
High humidity: additional moisture is absorbed Methods to Track the Passage of Capsules and Tablets through the
Becomes distorted and lose their rigid GIT to Map their Transit Time and Drug Release Patterns
shape
Remedy: use desiccant material (silica Gamma scintigraphy
gel, slay, or activated charcoal) Gamma ray emitting radiotracer incorporated into
Extreme dryness: moisture is lost the formulation with gamma camera coupled to a
Becomes brittle and crumble when data recording system
handled Pharmacoscintographic evaluation
IVIVC for bioavailability of immediate release
Gelatin Capsule products
Combination of scintigraphy and pharmacokinetic
Dissolves and exposes its contents studies
Unsuitable for aqueous liquids (softens gelatin and Assesses integrity and transit of time of enteric
distorted, resulting in leakage of contents) coated tablets through the stomach to the
intestines
Additives Drug and dosage form evaluation in new product
development
Desiccant Heidelberg capsule (No. 0 gelatin capsule)
To protect against the absorption of atmospheric pH sensitive (non indigestible radio telemetric
moisture device)
Dried silica gel A non-radioactive means to measure solid dosage
Clay forms (fasting and non fasting human subjects)
Activated charcoal Gastric pH, gastric emptying time,
Diluents or filter gastric residence time
To produce the proper capsules fill volume
Provide cohesion to the powders Manufacture of Hard Gelatin Capsule Shells
For the transfer of the powder blend into the
capsule shells Manufactured in 2 sections:
Lactose Capsule body
Microcrystalline cellulose Shorter cap
Starch
Drug Absorption Depends on a Number of Factors
Excipients Added for Capsule Fill
Solubility of the drug
Wetting agents (Li2CO3) Type of product formulation (immediate release, modified
Added to capsule formulation to enhance drug enteric)
dissolution Gastrointestinal contents
Absorbent Physiologic character and response
Separates interacting agents
Absorbs any liquefied material that may form Innovations to Provide Distinctions (Distinctive Looking Capsules)
Magnesium carbonate
Kaolin or light MgO Pulvules
Disintegrants End of the body-producing peg is tapered while
To assist the break up and disintegration of the leaving the cap-making peg rounded
capsule’s contents in the stomach Spansule capsules
Pregelatinized starch Capsules with the ends of both the bodies and
Croscarmellose caps highly tapered
Sodium starch glycolate
Lubricant or glidant Innovations in Capsule Shell Designs
Enhances flow properties
Silicon dioxide Snap-fit
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Two halves of capsule shells positively joined Lack of homogeneity for low dose drugs
through locking grooves in the shell walls Results in significant therapeutic consequences
Ensure reliable closing of the filled capsule
Coni-snap Preformulation Studies
Rim of the capsule body is tapered slightly, not
straight Determine whether all of the formulation’s bulk powders
Reduces the risk of the capsule rims touching or Effectively blended together
joining Require reduction of particle size
Eliminates splitting (telescoping) and/or denting Other processes to achieve homogeneity
of capsule shell
Coni-snap supro Methods in Reducing Particle Size
Rim is tapered, upper capsule part extends
(rounded edge of lower surface is visible) Milling
Opening is difficult, lower surface less gripping Particles ranging from 50-1000 micrometer
to pull 2 halves apart Micronization
Increases security of contents and integrity of the Drugs of lower dose or when smaller particles are
capsule required
Eliminates splitting (telescoping) and/or denting Particles ranging from 1-20 micrometer
of capsule shell
Filling Hard Capsule Shells
***Check the book: coni-snap capsule parts, coni-snap and coni-snap
supro capsule sizes (as in actual size of capsule in relation to a quart) Use punch method
Steps:
Capsule Sizes Count the capsules
Powder encapsulated placed on a sheet of
000 15 grains 972mg (largest) clean paper or a glass or porcelain plate
00 10 grains 648mg Powder mixed formed into a cake depth of
0 7.5 grains 486mg approximately ¼ to 1/3 the length of the
1 5 grains 324mg capsule body
2 4 grains 259mg Empty capsule punched vertically into the
3 3 grains 194mg powder cake until filled
4 2 grains 130mg
5 1 grain 64.8mg (smallest) Process of Capsule Filling
Plate process Solids that may be Encapsulated into a Soft Gelatin Capsule
Uses set of molds to form capsules
Rotary die process Solutions in a suitable liquid solvent, suspensions, dry
Most commonly used powders, granules, pellets or small tablets
Rotary die machine
Liquid gelatin flowing from an overhead tank
into two continuous ribbons brought together Compendial Requirements for Capsules
between rotating die
More efficient and productive Added substances may only be used:
Results in bicolored capsules Harmless in the quantities used
Very accurate filling (+/-1-3%) Do not exceed the minimum amount required to
Reciprocating die process provide their intended effect
Norton capsule machine Do not impair the product’s bioavailability
Similar to rotary die (gelatin ribbons are formed) therapeutic efficacy or safety
Differs in encapsulating process Do not interfere with requisite compendial assays
Produced, filled and sealed in a continuous and tests
operation
Accogel capsule machine
Stern Machine Comparison Between Hard and Soft Capsules
Unlike the other fill dry powders into soft elastic
capsules Property Hard Capsule Soft Capsule
Also use liquids or liquids and powders as fill
Used to cover tablets with a gelatin film (geltabs) Shell Made of Gelatin,
Variety of shapes, sizes, color possible gelatin, sugar plasticizer
and powder (glycerin) or
polyhydric
Utilization of Soft Gelatin Capsules alcohol
(sorbitol) water
To contain a variety of liquid, pastry and dry fills and etc.,
colorants
Manufacturi Shells Shells and fill
Uses of Soft Gelatin Capsules ng processes produced made and
separately combined on
Water-immiscible volatile and nonvolatile liquids from the fill one and the
Vegetable and aromatic oils, aromatic and Continuous same process
aliphatic hydrocarbons, chlorinated dipping, line
hydrocarbons, ethers, esters, alcohols and organic drying, By: plate
acids removing and process, rotary
Water-miscible nonvolatile liquids joining of die process and
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capsules as peg reciprocating Contents of a specified number of capsules can
containing die process be removed
plates rotate in Empty capsule shells dissolved in the dissolution
and out of medium
gelatin bath Weight variation
Content Dry powders Liquids and Hard Capsules
or granules, semi-liquids, Individual weight of 10 capsules – weight of
pellet mixture, suspensions, empty shells = net weight of performed
paste, small pasty assay for content of active ingredient
capsule and materials, dry according to monograph
tablets powders and Soft capsules
preformed Same as above, cut open the capsule and the
tablets content is removed by dissolving with
Formulation 13%-16% More moisture suitable solvent
technology moisture Water content Content uniformity
content of fill not more Amount of active ingredient (determined by assay)
Moisture proof than 5% must be:
packaging Addition of Within 85% to 115%of the label claim for 9-
needed titanium 10 dosage units
Encapsulation dioxides or No unit outside the range of 70% to 125% of
using iron oxides for label claim
succinylated light sensitive Additional test are needed when 2-3 dosage
gelatin shells units are outside of the desired range but
Packed in within the stated extremes.
aluminum Weight variation and content uniformity: uniformity
blisters of dosage units can be determined
Encapsulation Content labeling requirement
uses Express the quantity of each active ingredient in per
succinylated, dosage unit
glycerol-free Stability testing
shell Factors like temperature, humidity, light, formulative
formulation, components and other container closure system using
addition of long term and accelerated stability tests
PVP to the fill Moisture permeation test
For single unit and unit-dose containers to assure
suitability for packaging
Containers for dispensing capsules Uses color revealing desiccant pellet for color change
Tight and weight changes
Well-closed
Light-resistant
In glass or plastic containers Examples of some official capsules: Table 7.2: memorize
Some with packets of desiccant (prevents
absorption of excessive moisture) Inspection
Unit dose and strip packaging of solid
dosage forms provides: Visual or electric inspection
o Sanitary handling of the To detect any flaws in the integrity and appearance of
medications the capsules
o Ease of identification Defective caps should be rejected.
o Security in accountability for CGMP regulations if number of production flaws is
medications excessive
The cause must be investigated, documented and steps
Disintegration test fop capsules
undertaken to correct the problem.
Uses basket rack assembly, immersed 30 times per
Counting
minute into a thermostatically controlled fluid (37 oC)
and observed over the time described in the individual
Community pharmacy
monograph
Counting small numbers of solid dosage units:
To satisfy the test, the capsules disintegrate
specifically designed trays are used
completely into a soft mass having no palpably firm
Spatula used to count and sweep the dosage units into
core and only some fragments of the gelatin shell
the trough until the desired number is reached
Dissolution test for capsules
Tray must be wiped clean after every use to prevent
USP Apparatus I (stainless steel basket on a stirrer
batch-to-batch contamination
shaft) and USP apparatus II ( using paddle as the
Industrial scale
stirrer): same apparatus for immediate release tablet
Use of automated pieces of equipment dosage units
If the capsule shells interfere with the chemical
into bulk containers
analysis before proceeding with the sampling and
chemical analysis:
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Packaging