Capsules

Question 1

Capsule

Answer 1

a solid dosage form in which medicinal agents and/or inert substances are enclosed in a small shell of gelatin

Question 2

Gelatin

Answer 2

protein obtained by partial hydrolysis of collagen derived form bovine or porcine skin and bone

• Derived from skin, has plasticity
• Derived from bone, has firmness

Bloom strength should be approximately 150-280g

• Stable in air when dry, but is subject to microbial decomposition when it becomes moist

Question 3

Non-animal derived alternatives of gelatin

Answer 3

Hydroxypropyl methylcellulose, starch and carrgeenan capsules

Question 4

Advantages of capsules

Answer 4

• Can be used to deliver powders, granules, beads and prefabricated tablets, semisolids and liquids that do not dissolve gelatin
• Can mask taste and odor of drug
• Are easy to swallow
• Generating, rate of drug absorption after oral administration : Capsule > tablet
• Can be administered orally, rectally and vaginally

Question 5

Disadvantages of capsules

Answer 5

• Sensitive to relative humidity
• Not suitable for liquids that dissolve gelatin
• Some can be tampered with

Question 6

Plasticizers

Answer 6

Reduce rigidity of gelatin, making it more pliable

Ex: Water, Sorbital and propylene glycol

Question 7

Preservatives

Answer 7

Reduce bacterial and fungal growth

Ex: Methylparaben and propylparaben

Question 8

Colorants

Answer 8

Change color

Ex: Azo and xanthene dyes and iron oxide pigments

Question 9

Opacifiers

Answer 9

Makes clear gelatin opaque, which can protect contents from light

Ex: Titanium dioxide

Question 10

Hard gelatin capsules

Answer 10

Made of gelatin, sugar and water, and may contain colorants, opaquants
and preservatives
Shells normally have moisture content of 13-16%
– If too dry it becomes brittle
– If too moist it becomes soft and sticky

Question 11

Hard gelatin capsules are made how

Answer 11

Manufactured in two parts:

1. Capsule body
2. Shorter cap

Produced by mechanical dipping and then spinning of pins or pegs into a
temperature-controlled (50 C) reservoir of melted gelatin mixture

The two parts overlap when joined, with the cap fitting snugly over the open end of
the capsule body

Question 12

Hard gelatin capsule sizes

Answer 12

Various sizes: 000 (largest) to 5 (smallest) for human use

• Largest size capsules carry more weight of drug

Question 13

Capsule sizes

Answer 13

• Capsules can be used to encapsulate between 65 and 1000 mg of powdered material
• Some patients have difficulty swallowing larger capsules
  -Some patients find smaller capsules hard to handle
• If the active drug powder is large, the total amount can be divided into two smaller
  capsules that are easier to swallow
• If the active drug powder is small, more diluent can be added to increase the size of a
  capsule for handling convenience

Question 14

Rule of sizes

Answer 14

When the bulk density of powders is between 0.4 and 0.8 g/mL w an average of 0.6 g/mL, the size of the capsule can be approximated by the rule of sixes

• Each grain is equivalent to 0.065 g or 65 mg

Number 6 - Capsule size = weight of powder in grains

For example 6 - Capsule size 1 is 5. So 5 grains = 325 mg of powdered drug can be filled in capsule size #1

Question 15

Rule of sevens

Answer 15

1. Convert weight of powder per capsule to grains (1 grain = 0.065 g);
2. subtract the number of grains from 7; and
3. match the result to the following list

Resulting number Capsule Size
-3 000
-2 00
-1 or 0 0
1 1
2 2

Method does not work if the resulting number is higher than 5 or lower than -3

Question 16

Preparation of hard gelatin capsules

Answer 16

1. developing and preparing the formulation and selecting capsule size
2. filling the capsule shells
3. capsule sealing (optional)
4. cleaning and polishing the filled capsules

Question 17

Formulation for hard capsules

Answer 17

prepare a capsule with accurate dosage, good bioavailability, ease of filling
and production, stability and elegance
Suitable for dry formulations; active and inactive components must be blended
thoroughly to ensure a uniform powder mix for the fill

Question 18

Inactive components (or excipients) important in the manufacture of hard capsules

Answer 18

1. Diluent (or filler)- for adding bulk and cohesion to the powders
   Ex: Lactose, microcrystalline
   cellulose and starch
2. Disintegrants- to assist breakup and distribution of capsule contents in the stomach
   Ex: Pregelatinized starch, croscarmellose and sodium starch glycolate
3. Lubricant, to enhance flow properties of powder or granule for ease of filling
   Ex: Fumed silicon
   dioxide, magnesium stearate and talc
4. Surfactant- to improve water penetration into the powder
   Ex: Sodium lauryl sulfate and
   polysorbate 80

Question 19

Formulation for hard capsule pt 2

Answer 19

Some liquids, such as oils, that do not interfere with the stability of the
capsule, may be placed in locking or sealed hard capsules
Liquid may be mixed with an inert powder to make a wet paste, and then
inserted
Eutectic mixtures may be mixed with diluent or absorbent such as magnesium
carbonate, kaolin or light magnesium oxide which will separate the interacting
agents in order to absorb the liquefied material that forms
NOT suitable for aqueous liquids
- soft gelatins and distorts, resulting in leakage of contents

Question 20

Extemporaneous filling of capsules

Answer 20

Filled capsules should be neither underfilled nor overfilled, but should hold the ingredients snugly
Capsule size should be selected that accommodates the fill and will be easily swallowed

Question 21

The steps used in calculating the proper capsule fill

Answer 21

1. Select appropriate capsule size
2. Fill the capsule shell separately with each drug and diluent, and record weights of each
3. Calculate diluent displacement weight for each drug
4. Calculate the amount of diluent required per capsule
5. Calculate the total quantities of each drug and the diluent needed to fill all of the capsules
   prescribed

Question 22

Punch method

Answer 22

when calculating the amount of drug substance and
diluent required, usually an extra dose (an additional 5-10% of the formulation) is
added to account for ingredient loss during filling
In Pharmaceutics and Skills Lab, we will account for 2 extra capsules or 10% excess,
whichever is greater

Question 23

Geometric dilution

Answer 23

ensures that drugs are distributed uniformly throughout the mix

Question 24

Filling hard gelatin capsules via “punch method”

Answer 24

1. Nitrile gloves should be worn to avoid fingerprints on the capsules
2. The powder mixture is placed on the sheet of clean paper, glass or porcelain pill tile
3. With a spatula, the powder is shaped into a cake having a depth of approximately 1/4
   to 1/3 the length of the capsule;
4. Remove the capsule cap from the capsule body
5. The empty capsule body is held between the thumb and forefinger and is punched
   vertically into the powder cake with a slight twist motion; repeat until the capsule is
   filled to ensure equal and accurate filling
6. Replace the capsule cap and tap the capsule on the cap end to distribute the
   contents evenly
7. You should try to note signs such as “crunching” of the powder as the capsule fills
   and the pressure needed to fill each capsule; these will be useful indicators, which
   can help you in filling the capsule consistently
8. The capsules should be weighed to assure consistency of weight
9. The final step of filling a capsule is to polish the capsules with a paper towel to
   remove any powder from the outside of the capsule

Question 25

Capsule filling machine

Answer 25

Large quantities of various capsules can be compounded in a very short amount of time the compounder should NOT calculate and use excess powder; loss of powder is minimal, and since all powder must be packed into the capsules, the risk of overdosing is great

Question 26

Soft gelatin capsules

Answer 26

Soft capsules contain appreciable quantities of a plasticizer other than water which makes the gelatin is more flexible - Must be compatible with gelatin - Can be oblong, oval or round -Typically formed, filled and sealed in one continuous operation

Question 27

Liquids that may be encapsulated | into soft capsules

Answer 27

1. Water-immiscible volatile and nonvolatile liquids 2. Water-miscible nonvolatile liquids 3. Water-miscible and relatively nonvolatile compounds Liquids that can easily migrate through the capsule shell are NOT suitable; these materials include water above 5% and low-molecular-weight water-soluble and volatile organic compounds

Question 28

Preparation of soft gelatin capsules

Answer 28

Plate process and rotary die process

Question 29

Plate process

Answer 29

1. Warm sheet of gelatin placed on bottom plate of mold. 2. Medication-containing liquid evenly poured on it 3. A second sheet of gelatin placed on top of the medication 4. Top plate of the mold put on top 5. Pressure is applied to the mold to form, fill and seal the capsules simultaneously, the capsule removed and washed with a solvent harmless to the capsules

Question 30

Rotary die process

Answer 30

- Most commonly prepared using this method - Liquid gelatin flowing from an overhead tank is formed into two continuous ribbons by the rotary die machine and brought together between twin rotating dies, metered fill material is injected between the ribbons precisely at the moment that the dies form pockets of the gelatin ribbon, these pockets of fill-containing gelatin are sealed by pressure and heat and then severed from the ribbon - The reciprocating die process is similar in that ribbons of gelatin are formed to encapsulate the fill, but it differs in the encapsulating process

Question 31

Substances added to enhance stability, usefulness, elegance, or to facilitate their manufacture, may be used ONLY if they:

Answer 31

1. Are harmless in the quantities used 2. Do not exceed the minimum amounts required to provide their intended effect 3. Do not impair the product’s bioavailability, therapeutic efficacy or safety 4. Do not interfere with requisite compendial assays and tests

Question 32

Disintegration test for hard and soft capsules

Answer 32

they are placed in basket assembly, which is immersed 30 times per minute into fluid at 37 °C, and observed over time until capsules disintegrate completely into a soft mass with no firm core and only some fragments of the gelatin shell

Question 33

Dissolution test for capsules

Answer 33

Using special apparatus and dissolution medium to predict how the solid will enter solution in vivo; in cases where shell interferes, contents of a specified number of capsules can be removed and the empty shell dissolved before proceeding with the sampling and chemical analysis

Question 34

Weight variation for hard capsules

Answer 34

To determine content of the active ingredient – Hard capsules – 10 capsules are individually weighed and their contents removed, the emptied shells are individually weighed and the net weight of the contents are calculated by subtraction

Question 35

Weight variation for soft capsules

Answer 35

– Soft capsules – The gross weight of 10 intact capsules is determined individually - Then each capsule is cut open and the contents are removed by washing with a suitable solvent, the solvent allowed to evaporate, individual shells are weighed and net contents calculated

Question 36

Content uniformity

Answer 36

The quantity of each active ingredient must be within the range of 85-115% of the label claim for 9 of 10 dosage units assayed, with no unit outside the range of 70- 125% of the label claim

Question 37

Content labeling

Answer 37

All capsules must be labeled to express quantity of each active ingredient

Question 38

Stability testing

Answer 38

Intrinsic stability of the active drug molecule and the influence of environmental factors like temperature, humidity, and light are determined The battery of stress testing, long-term stability and accelerated stability tests help determine appropriate conditions for storage and the product’s anticipated shelf-life

Question 39

Moisture permeation test

Answer 39

Degree and rate of moisture penetration are determined by packaging the dosage unit together with a color-revealing desiccant pellet Exposing the packaged unit to known relative humidity over a specified time Then we observe the desiccant pellet for color change (indicating the absorption of moisture) and comparing the pretest and posttest weight of the packaged unit This assures suitability of packaging

Question 40

Inspecting, counting, packaging and storing capsules

Answer 40

Should be uniform in appearance; visual or electronic inspection should be undertaken to detect any flaws May be counted manually using a specially designed tray, such as the Abbott Sanitary Counting Tray, or by automated equipment Packaged in glass or in plastic containers, some containing packets of a desiccant to prevent absorption of excessive moisture, and should be stored in tightly capped containers in a cool, dry place