Capsules

Question 1

Capsules
List and explain the Finished product QC tests

Answer 1

1. Permeability and sealing
2. Potency and impurity content
3. Average weight and weight variation
4. Uniformity of content
5. Disintegration (media varies depending capsule type)
6. Dissolution, similar drug release characteristics between batches, and similar to batches which were clinically effective.
7. Moisture content (Karl Fisher titrimetry, correlation with degradation profile, drug release characteristics)
8. Microbial content

Question 2

Name the In-process tests (5) for soft gelatin capsules

Answer 2

Gel ribbon thickness and uniformity across the ribbon
Seal thickness
Weight of the capsule fill and variation capsule to capsule
Weight of the capsule shell and variation capsule to capsule
Moisture level of the capsule shell before and after drying

Question 3

Explain the key in-process tests for hard shell gelatin capsules?

Answer 3

Visual inspection, fill weight and fill-weight uniformity

Question 4

Why should highly soluble chloride salts not be dispensed in hard gelatin capsules?

Answer 4

The capsule shell will disintegrate. Highly soluble salts of drugs (bromides, iodides, chlorides) of drugs are generally not formulated in hard gelatin capsules because these can draw moisture from the shell, thus making it brittle.

Question 5

Name an alternative to hard gelatin capsule?

Answer 5

HPMC (Hydroxypropyl Methylcellulose) (plant based)

Question 6

List benefits of HPMC shells?

Answer 6

HPMC: Provide health-conscious consumers with a natural, 100% vegetable-derived alternative to animal-derived capsules.
Ideal for individuals with religion-based dietary restrictions.
Offer the ability to address today’s API challenges as well as the requirement for rapid product development.
Can withstand high temperature and humidity conditions, protecting their content from all kinds of fluctuations; this makes them ideal for hygroscopic formulations.

Question 7

List benefits of gelatin shells?

Answer 7

Most common type of capsule used in the pharmaceutical industry.
Flexible option that works for a wide range of formulations and applications.
With the addition of custom flavors, can mask the unpleasant smell and taste of the encapsulated drug.
Recognized by most of the world’s regulatory authorities as “Generally Recognized as Safe (GRAS)” for human consumption.
Do not contain GMOs, are completely natural, and are allergen free.
Remarkable cost efficiency: the production cost of gelatin capsules is at least 30% lower than other alternatives.

Question 9

What is the main difference between soft and hard gelatin capsules?

Answer 9

Level of plasticiser.

Question 10

Leakage from soft gelatin capsules can be caused by:

a. Hydrolysis of gelatin at low pH
b. Addition of surfactants
c. addition of polyethylene glycol
d. all of the above

Question 11

The ideal powder characteristics for successful filling of hard gelatin capsules include:

Question 13

Common capsule deflects

Answer 13

First, before filling the machine’s hopper with empty capsules, verify that the capsules meet your dimensional specifications by checking a representative sample. Even capsules from the most reputable manufacturers may differ slightly. The same is true of tooling supplied by different vendors, so be prepared to make some adjustments. Of course, verify your settings and check that routine maintenance has been performed before you start. And be sure you understand how the active ingredient and/or formulation can affect filling.

Next, check the environmental conditions within filling room. Ideal conditions are a temperature of 22°C ±2° and a relative humidity of 40 to 50 percent. If conditions are outside these ranges, allow some time for the room and the materials within it acclimate before you begin production. If defects occur, try resolving the problem using one or more of these troubleshooting tips. Lumpy or misshaped capsules

If the capsules form lumps or are otherwise misshaped, check the conditions under which they were transported or stored. Empty capsules should be maintained at a temperature between 15° and 30°C and a relative humidity between 40 and 65 percent. Avoid exposing empty capsules to a direct source of light or to heat. Do not transfer capsules suddenly from a high-temperature environment to a low-temperature one.

Improper Rectification
If the capsules are not being oriented properly (cap up), first make sure no one is using a plastic container to transport the capsules or a plastic scoop to load the capsule filler. Plastic can cause an electrostatic charge to develop, hindering rectification. Use stainless steel containers and scoops instead. Also check the gate knee and adjust it as necessary. Verify that the stroke of the pushers, or fingers, is set properly according to the joined length of the shells. Also check that the raceway is in good condition.

Failure to Separate
If the caps and bodies fail to separate, check the the vacuum. On most capsule fillers, the gauge should read somewhere between 15 and 18 inches mercury. You many also need to adjust the gap between the machine’s cap segments and body segments. Check the timing of the solenoid valve and how well the segments’ holes align with the raceway fingers. Check the filter bag and clean it periodically.

Dented Capsules
Dents can form on the dome of the cap and/or body for a variety of reasons. One cause is improper setup that leads to the machine applying excessive pressure. To determine the correct setting, manually lock 20 capsules together and measure their length. Next, find the mean value and adjust the machine to that value with the help of a tie rod. Another reason for dented capsules is overfilling. To correct this, weigh 20 filled capsules. The average weight should not exceed the specified volume of the capsules you’re using. If it does, consider using larger capsules.

Telescoping
This defect occurs when the cap and body misalign and the capsule body splits and a portion of it covers the cap. To eliminate this defect, make sure all the capsules are perfectly round. Also check the alignment of the cap and body bushings, or segments, using a gauge designed for that purpose. The environmental conditions in the filling room can also contribute to this problem. If the machine must be stopped for more than 30 minutes, protect the capsule shells from direct exposure to the environment.

Popping
If the capsules open or elongate after filling, it’s likely due to excessive locking pressure or overfilling. It’s also possible that the locking mechanism is weak, but that’s a defect rarely seen in capsules supplied by reputable manufacturers.

Brittleness
Check your storage conditions. When capsules lose moisture, often due to poor storage practices, they become brittle. The threshold is approximately 12.5 percent moisture. Anything less will likely lead to brittleness. Filled capsules that include a hygroscopic active or excipient can also cause brittleness. Capsules made from HPMC are less likely to become brittle.