Pharmaceutics II: Capsules
A pharmacist receives a prescription for 15 mg piroxicam capsules, qty. 48. A #1 capsule filled with piroxicam weighs 245 mg; a capsule filled with lactose weighs 180 mg. How much piroxicam and lactose are required for the prescription? Prepare sufficient powder for 50 capsules (2 extra). A. 15 mg piroxicam + 165 mg lactose B. 750 mg piroxicam + 9.00 g lactose C. 750 mg piroxicam + 8.45g lactose D. 15 mg piroxicam + 230 mg lactose E. None of the above
C. 750 mg piroxicam + 8.45g lactose
Capsule quality control: Content uniformity
At least 9/10 should be within ± 15% (85-115% of label claim, n=10).
Capsule quality control: Stability testing
accelerated, environmental factors, container/closure
Gelatin is sold by its strength known as
"Bloom"
Disadvantages of soft gel capsules
-- Cost -- No liquids that easily migrate through the capsule shell can be used (for example: Water>5%, low MW water-soluble and volatile compounds)
The manufacturing process of empty capsules:
-- Dipping & rotation/spinning -- Drying --Trimming: Stripping/Cutting -- Joining
Evaluation/ Capsule quality control
-- Dissolution -- Weight variation -- Content uniformity -- Stability testing -- Moisture permeation test
Capsule Disadvantages
-- Forbidden drugs (e.g. sulfa drugs) => incompatibility. -- Large Size "0" difficult to swallow -- Bolus effect in multiple therapy (polypharmacy): multiple side effects -- Storage in controlled environment (dessicant required)- too much moisture
EMPTY GELATIN CAPSULE SHELL COMPOSITION: soft gelatin capsule
-- Gelatin -- Plasticizers (glycerin, sorbitol): make shell elastic -- Water: approx 23%= need for preservatives (parabens, sorbic acid) -- Colorants -- Opaquants
EMPTY GELATIN CAPSULE SHELL COMPOSITION: hard gelatin capsule
-- Gelatin -- Sucrose (sugar) -- Water: 13-16% -- Colorants -- Opaquants (Titanium dioxide): blocks light
Substitutes for vegetarians
-- Hydroxy propyl methyl celllose (HPMC) -- hydroxy propyl cellulose (HPC) capsules. -- Agar-agar for food
Capsule Advantages
-- Improved palatability (taste/smell, swallow with food) -- Drug readily bioavailable -- Versatile: liquid/solid, soft/hard capsules -- Placebo therapy in clinical trial (e.g. inactives) -- Easy compounding (for hard capsules) -- Alterable to individual needs --Drug protection (color/light)
Advantages of soft gelatin capsules
-- Masks unpleasant liquid taste and odor -- Sealed to protect from air and environmental contaminants -- Gelatin shell can be formulated to block out UV light -- Tamper evident -- Shell can be produced in many colors or combinations of two colors with varying degrees of transparency or opacity -- Portability of liquid dosage forms -- Pharmaceutically elegant, easy to swallow, consumer preferred -- Faster acting -- Predissolved fill may offer greater availability -- Offers precise fill volume delivering accurate dosage -- Custom sizes and shapes appropriate for oral, topical, chewable, and suppository delivery
Medium Bloom vs High Bloom
-- Medium Bloom #: 175-225 -- High Bloom #: 225-325 (forms gel faster)
Drug release: matrix water soluble
-- faster dissolution
Capsule quality control: Disintegration Test
-- perform if the capsules are enteric coated . Shell normally should dissolve in 10 min. Example: Erthromycin delayed release capsules.
Variables of capsules
-- sizes -- lengths -- diameter -- capacity -- thickness of shell -- colors
Drug release: matrix water insoluble
-- slower dissolution
Bloom strengths that are most suitable for pharmaceutical capsules:
150 to 280
Formula for fill weight:
= density x volume -- density= mass (weight)/ volume
Which capsule size has the smallest capacity? A) 5 B) 4 C) 2 E) 0
A) 5
The shells of soft gelatin capsules may be made elastic or plastic by the addition of? A) Sorbitol B) Povidone C) Polyethylene glycol D) HPMC
A) Sorbitol
Tamper evident capsules
Cap and body sealed with a colored band of gelatin for tamper or leak proof
Capsule quality control: Weight variation
Each capsule should be within ± 10% of the average weight (n= 20 capsules).
How is gelatin obtained?
Gelatin USP obtained by partial hydrolysis of collagen tissue composed of glycine, glutamic acid and proline. -- Type A (pork skin) and Type B (calf skin)
What are the two types o gelatin capsules?
Hard gelatin capsules (HGC) Soft gelatin capsules (SGC)
Shapes of SGC
Oblong, elliptical, spherical, etc. and can carry liquids, suspensions, pastes, dry powders
Goals of formulation:
Prepare a capsule with a) accurate dosage: all capsules should be the same b) good bioavailability: drug absorbed c) ease of filling & production: powder formulation flow well d) stability & elegance.
SGC are prepared, filled, and sealed all in a continuous operation using a special equipments like:
Rotary die process
Capsules
SDF in which one or more medicinal (API) and inert excipients are enclosed within a small soluble (gelatin) shell
HGC formulations are prepared in four steps:
Step 1. Developing the formulation & Capsule size Step 2. Filling HGC ("punch" method or Automated machines. Approx. 3000 capsules/min) Step 3. Capsule sealing (spot-welding, match-locking body/cap, tamper-resistant gelatin band) Step 4. Cleaning and polishing (cloth, vacuum, brush + granular of pan polishing).
The higher a bloom value, the ____________ (higher or lower) the melting and gelling points of a gel and the _____________ (shorter or longer) its gelling times
The higher a Bloom value, the higher the melting and gelling points of a gel, and the shorter its gelling times.
Gelometer:
The test determines the weight in grams needed by a specified plunger (normally with a diameter of 0.5 inch) to depress the surface of the gel by 4 mm without breaking it at a specified temperature. The number of grams is called the Bloom value.
Capsule quality control: Dissolution
USP method
Why can different types of powders with different amounts occupy the same size capsule?
because of the drug's densities
HGC are manufactured in two sections (parts):
body and a cap.
It is important to control __________ and _______________ of excipients and drug for content uniformity.
density and particle size
Examples of HGC: Dexmethylphenidate/Focalin XR 5-40 mg ER Capsules
for + 6 years ADHD Note: No crushing or chewing => Dose dumping and side effect (e.g. jitteriness syndrome = early worsening of anxiety, agitation, and irritability)
Capsule quality control: Moisture permeation test
for container/packaging with a color revealing desiccant pellet -- test to make sure the capsules are placed in appropriate packaging
Lubricants
for ease the ejection of plugs
Glidants:
improve the fluidity of powders
Fillers (diluents):
increase the bulk of the formulation
Surfactant/Wetting agents
increase the wetting of the powder and enhance dissolution.
Sorbitol
is added to render the gelatin elastic and plastic-like -- also glycerin
Anything made with water is subject to:
microbial growth
Particle size reduction is done by
milling or micronization
Composition of capsule shell
mixture of gelatin, sugar, and water -- depends on if HGC or SGC
Adsorbents
to carry eutectic mixtures that tend to liquefy or for liquid drugs.
Disintegrants
to overcome the cohesive strength