Aira Jhamaica DImacale Provide prolonged release of the medication

Sublingual or buccal tablets

Pharmaceutical Dosage To dissolve under the tongue or in the mouth
Chapter 7: Capsules Alternative Products if Patients cannot Swallow an Intact Solid Dosage
Form
Capsules and Tablets
Chewable tablet
Preferred when administered orally by adults: conveniently
Instant dissolving tablet
carried, readily identified, easily taken
Oral liquid
Variety of dosage strengths, providing:
Oral or nasal inhalation solution
Flexibility to the prescriber
Accurate individualized dosage for the patient Suppository
Packaged and shipped by manufacturers at lower cost Injection
and with less breakage than comparable liquid forms
More stable and have a longer shelf life Characteristics

Pharmaceutical Standpoints May be swallowed whole by patient

May be inserted into the rectum for drug release and absorption
Solid dosage forms: from site
Manufactured efficiently and productively The content may be removed from the gelatin shell and
Packaged and shipped at lower cost and with less employed as pre measured medicinal powder, the capsule shell
breakage being use to contain a dose of the medicinal substance.
More stable Ex: Theo-dur Sprinkle
Have longer shelf life than liquids Elegance
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 buy
Formulation difficulties 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 manufacturers 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 individualized
thickness, etc) 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
Masking of taste and odor Hard Gelatin Capsules
Pharmaceutically elegant
Production economically sound Also referred to as DFC Dry Filled Capsule, 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 enclosed in a For extemporaneous compounding of prescriptions
small shell of gelatin Contains 13% to 16% moisture
Swallowed wholly Manufactured form:
Open capsule or crushed tablets Gelatin
Mixed with food or drink (children or patients who are Titanium dioxide (opacifying agent)
unable to swallow solid dosage forms) 0.15% SO2 (prevents decomposition of gelatin)
Colorants
Solid Dosage Forms that must be Left Intact
Empty Capsule Shells
Enteric coated tablets
To pass through the stomach for drug release and Made of gelatin, sugar and water
absorption in the intestine Hard or soft
Extended-release dosage forms

1
 Softened (made elastic or plasticized) by adding glycerin or
polyhydric alcohol like sorbitol)
Can be: clear, colorless, tasteless
Colored with various FD&C and D&C dyes
Made opaque by adding agents like titanium oxide
Gelatin
Obtained by partial hydrolysis of collagen from the skin, white
connective tissue and bones of animals
Properties:
Fixed or Volatile Oils
Stable in air (dry)
Subject to microbial decompositions when moistened
Insoluble in cold water, softens through absorption of
up to 10 times its weight of water Eutectic Mixture of Drugs
Soluble in hot water and in warm gastric fluid
A protein, digested by proteolytic enzymes and
absorbed
High humidity: additional moisture is absorbed
Becomes distorted and lose their rigid shape Methods to Track the Passage of Capsules and Tablets through the GIT to
Remedy: use desiccant material (silica gel, Map their Transit Time and Drug Release Patterns
slay, or activated charcoal)
Extreme dryness: moisture is lost
Becomes brittle and crumble when handled
Gelatin Capsule
Dissolves and exposes its contents
Unsuitable for aqueous liquids (softens gelatin and distorted,
resulting in leakage of contents)
Additives
Desiccant
To protect against the absorption of atmospheric
moisture
Dried silica gel
Clay
Activated charcoal
Diluents or filter
To produce the proper capsules fill volume
Provide cohesion to the powders
For the transfer of the powder blend into the capsule Manufacture of Hard Gelatin Capsule Shells
shells
Lactose
Microcrystalline cellulose
Starch
To assist the break up and disintegration of the
capsules contents in the stomach
Pregelatinized starch
Croscarmellose
Sodium starch glycolate
Lubricant or glidant
Enhances flow properties
Silicon dioxide
Magnesium stearate
Stearic acid or talc (about 0.25-1%)
Surface active agent (surfactant)
To facilitate wetting by GI fluids
Sodium lauryl sulfate
Do not interfere with stability of the gelatin shells
Mixtures of agents that have a propensity to liquefy when
admixed
Gamma scintigraphy
Gamma ray emitting radiotracer incorporated into the
formulation with gamma camera coupled to a data
recording system
Pharmacoscintographic evaluation
IVIVC for bioavailability of immediate release
products
Combination of scintigraphy and pharmacokinetic
studies
Assesses integrity and transit of time of enteric coated
tablets through the stomach to the intestines
Drug and dosage form evaluation in new product
development
Heidelberg capsule (No. 0 gelatin capsule)
pH sensitive (non indigestible radio telemetric device)
A non-radioactive means to measure solid dosage
forms (fasting and non fasting human subjects)
Gastric pH, gastric emptying time, gastric
residence time
Manufactured in 2 sections:
Capsule body
Shorter cap

Excipients Added for Capsule Fill Drug Absorption Depends on a Number of Factors

Wetting agents (Li2CO3) Solubility of the drug

Added to capsule formulation to enhance drug Type of product formulation (immediate release, modified
dissolution enteric)
Absorbent Gastrointestinal contents
Separates interacting agents Physiologic character and response
Absorbs any liquefied material that may form
Magnesium carbonate Innovations to Provide Distinctions (Distinctive Looking Capsules)
Kaolin or light MgO
Pulvules
Disintegrants
2
 End of the body-producing peg is tapered while
leaving the cap-making peg rounded
Spansule capsules
Capsules with the ends of both the bodies and caps
highly tapered
Innovations in Capsule Shell Designs
Dry Formulations
Snap-fit
Two halves of capsule shells positively joined through
locking grooves in the shell walls
Ensure reliable closing of the filled capsule
Coni-snap
Rim of the capsule body is tapered slightly, not
straight
Reduces the risk of the capsule rims touching or
joining
Eliminates splitting (telescoping) and/or denting of
capsule shell
Coni-snap supro
Rim is tapered, upper capsule part extends (rounded
edge of lower surface is visible)
Opening is difficult, lower surface less gripping to pull
2 halves apart
Increases security of contents and integrity of the
capsule
Eliminates splitting (telescoping) and/or denting of
capsule shell
***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)
Goals in preparing a capsule:
Accurate dosage
Good availability
Ease of filling and production
Stability
Elegance
Blended thoroughly (active and inactive components) to ensure
uniformity of powder mix for the fill
Care in Blending
Lack of homogeneity for low dose drugs
Results in significant therapeutic consequences
Preformulation Studies
Determine whether all of the formulations bulk powders
Effectively blended together
Require reduction of particle size
Other processes to achieve homogeneity
Methods in Reducing Particle Size
Milling
Particles ranging from 50-1000 micrometer
Micronization
Drugs of lower dose or when smaller particles are
required
Particles ranging from 1-20 micrometer

Capsule Sizes Filling Hard Capsule Shells

000 15 grains Use punch method

00 10 grains Steps:
0 7.5 grains Count the capsules
1 5 grains Powder encapsulated placed on a sheet of clean
2 4 grains paper or a glass or porcelain plate
3 3 grains Powder mixed formed into a cake depth of
4 2 grains approximately to 1/3 the length of the capsule
5 1 grain body
Empty capsule punched vertically into the
powder cake until filled
Preparation of Filled Hard Gelatin Capsules
Process of Capsule Filling
Formulation development and preparation and selection of
capsule size Milling or sieving of all ingredients
Filling the capsule shells Blending
Capsule sealing (optional) Powder blender or empty capsules
Cleaning and polishing of filled capsules Capsule filler
Capsule deduster or cleaner
Examples of Fill in Hard Gelatin Capsules
Capsule injection screen
Powder or granulate Capsule check-weighing system or reject
Pellet mixture Finished capsules
Paste Packaging
Capsule
***Check book: profill system
Tablet
Capsule Sealing
Developing the Formulation and Selection of Capsule Size
For the manufacturers:

3
 Sealing the joint between the 2 capsule parts using: Utilization of Soft Gelatin Capsules
Colored band of gelatin (KAPSEALS,
Parker Davis) To contain a variety of liquid, pastry and dry fills
Heat welding process
o Fuses the capsule cap to the body
through the double wall thicknessUses of Soft Gelatin Capsules
at their juncture (distinctive ring
around the capsule) Water-immiscible volatile and nonvolatile liquids
Liquid wetting agent (liquid sealing-water Vegetable and aromatic oils, aromatic and aliphatic
and ethanol sprayed around the seam area), hydrocarbons, chlorinated hydrocarbons, ethers,
followed by thermal bonding esters, alcohols and organic acids
Extemporaneously Water-miscible nonvolatile liquids
o Warm gelatin solution, lightly Polyethylene glycols and nonionic surface active
coating the inner surface of the agents as polysorbate 80
cap prior to placement on the Water-miscible and relatively nonvolatile compounds
filled capsule body Propylene glycol and isopropyl alcohol (depending on
factors as concentration used and packaging
Cleaning and Polishing Capsules conditions)

Small scale
By rubbing with a clean gauze or cloth Soft Medications Commercially Prepared into Soft Gelatin Capsules
Large scale
Cleaning vacuum affixed to the capsule-filling Acetazolamide: Diamox sequels: Carbonic anhydrase inhibitor
machines (removes any extraneous material) using Cyclosporine: Sandimmune, Neoral: Immunosuppressive
Accela-Cota apparatus Ethosuximide: Zarontin: Anticonvulsant
Ranitidine HCl: Zantac Geldose: Histamine H2 receptor inhibitor
Some Medications Commercially Prepared into Soft Gelatin Capsules

Acetazolamide: Diamox: Carbonic anhydrase inhibitor
Cyclosporine: Sandimmune: Immunosuppressive
Cyclosporine: Neoral: Immunosuppressive
Digoxin: Lanoxicaps: Cardiac glycoside
Ethosuximide: Zarontin: Anticonvulsant
Ranitidine HCl: Zantac Geldose: Histamine H2 receptor inhibitor
Liquids that cannot be Encapsulated into a Soft Gelatin Capsule
Easily migrate through capsule shell like materials with water
above 5%
Low molecular weight
Water soluble and water volatile organic compounds (alcohols,
ketones, acids, amine, and esters)

Preparation of Soft Gelatin Capsules

Solids that may be Encapsulated into a Soft Gelatin Capsule
Plate process
Uses set of molds to form capsules Solutions in a suitable liquid solvent, suspensions, dry powders,
Rotary die process granules, pellets or small tablets
Most commonly used
Rotary die machine Compendial Requirements for Capsules
Liquid gelatin flowing from an overhead tank into two
continuous ribbons brought together between rotating Added substances may only be used:
die Harmless in the quantities used
More efficient and productive Do not exceed the minimum amount required to
Results in bicolored capsules provide their intended effect
Very accurate filling (+/-1-3%) Do not impair the products bioavailability therapeutic
Reciprocating die process efficacy or safety
Norton capsule machine Do not interfere with requisite compendial assays and
Similar to rotary die (gelatin ribbons are formed) tests
Differs in encapsulating process
Produced, filled and sealed in a continuous operation
Accogel capsule machine
Stern Machine
Unlike the other fill dry powders into soft elastic
capsules
Also use liquids or liquids and powders as fill
Used to cover tablets with a gelatin film (geltabs)
Variety of shapes, sizes, color possible

4
 Dissolution test for capsules
USP Apparatus I (stainless steel basket on a stirrer shaft)
and USP apparatus II ( using paddle as the stirrer): same
apparatus for immediate release tablet
If the capsule shells interfere with the chemical analysis
before proceeding with the sampling and chemical analysis:
Contents of a specified number of capsules can be
removed
Empty capsule shells dissolved in the dissolution
medium
Weight variation
Hard Capsules
Individual weight of 10 capsules weight of
empty shells = net weight of performed assay for
content of active ingredient according to
Comparison Between Hard and Soft Capsules monograph
Soft capsules
perty Hard Capsule Soft Capsule Same as above, cut open the capsule and the
content is removed by dissolving with suitable
hell Made of gelatin, sugar and Gelatin, plasticizer (glycerin) or solvent
powder polyhydric alcohol
(sorbitol)
Content uniformity
water and etc., colorants
Amount of active ingredient (determined by assay) must
ng processes Shells produced separately from Shells and fill made be: and
the fill combined on one and the same Within 85% to 115%of the label claim for 9-10
Continuous dipping, drying, process line dosage units
removing and joining of capsules By: plate process, rotary die No unit outside the range of 70% to 125% of
as peg containing plates rotate in process and reciprocating die label claim
and out of gelatin bath process Additional test are needed when 2-3 dosage units
ntent Dry powders or granules, pellet Liquids and semi-liquids, are outside of the desired range but within the
mixture, paste, small capsule and suspensions, pasty materials, dry stated extremes.
tablets powders and preformed tablets
Weight variation and content uniformity: uniformity of
n technology 13%-16% moisture content More moisture dosage units can be determined
Moisture proof packaging needed Water content of fill not labeling
Content more requirement
Encapsulation using succinylated than 5% Express the quantity of each active ingredient in per dosage
gelatin Addition of titanium dioxides
unit or
iron oxides for light sensitive
Stability testing
shells Factors like temperature, humidity, light, formulative
Packed in aluminum blisterscomponents and other container closure system using long
term and accelerated stability tests
Encapsulation uses succinylated,

glycerol-free shell Moisture permeation test
formulation,
addition of PVP to the
fillFor single unit and unit-dose containers to assure suitability
for packaging
Uses color revealing desiccant pellet for color change and
Containers for dispensing capsules weight changes
Tight
Well-closed
Light-resistant
In glass or plastic containers
Some with packets of desiccant (prevents
absorption of excessive moisture)
Examples of some official capsules: Table 7.2: memorize
Unit dose and strip packaging of solid dosage
forms provides: Inspection
o Sanitary handling of the medications
o Ease of identification Visual or electric inspection
o Security in accountability for To detect any flaws in the integrity and appearance of the
medications capsules
Disintegration test fop capsules Defective caps should be rejected.
Uses basket rack assembly, immersed 30 times per minute CGMP regulations if number of production flaws is excessive
into a thermostatically controlled fluid (37oC) and observed The cause must be investigated, documented and steps
over the time described in the individual monograph
undertaken to correct the problem.
To satisfy the test, the capsules disintegrate completely into
Counting
a soft mass having no palpably firm core and only some
fragments of the gelatin shell
Community pharmacy
5
 Counting small numbers of solid dosage units: specifically
designed trays are used
Spatula used to count and sweep the dosage units into the
trough until the desired number is reached
Tray must be wiped clean after every use to prevent batch- Storage
to-batch contamination
Industrial scale
Use of automated pieces of equipment dosage units into
bulk containers
Unit dose and strip packaging of solid dosage forms
Provides sanitary handling of the medications
Ease of identification
Security in accountability for medication
Caps should be stored in tightly capped containers in a cool, dry
place.

Packaging

Caps are packaged in:

Glass or in plastic containers
Some containing packets of desiccant ( prevent absorption
of excessive moisture)