Capsules

When can substances be added to capsule?

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

Hard Gelatin Capsule Components

- Cap (shorter) - Body (longer)

What happens to HGC when stored in high humidity?

- Capsules absorb the extra moisture and become misshapen - May affect hygroscopic agents within capsules - Alters drug absorption

Inspecting, counting, packaging, storing capsules

- Capsules should be uniform in appearance - Defective capsules should be rejected - CGMP regulations require that if the number of production flaws is excessive, it must be investigated and fixed - In the pharmacy, capsules may be counted on a tray or using an automated device

What other ingredients can capsule shell be made of?

- Cellulose polymers - other suitable materials

Risk of taking a medication without enough fluid

- Esophageal ulceration - Alendronate, ASA, NSAID, KCl, tetracycline

HGCs Size

- Final determination of size capsule to used depends on: 1. Density and compressibility of the fill material 2. Comparison may be made with powders of well-known features - Larger size = smaller volume/capacity

Packaging of capsules

- Glass or plastic bottles - Desiccant is used to prevent absorption of excessive moitures

Gelatin capsule shell typed

- Hard shells (2 pieces - Soft shells (1 piece)

Disintegrants

- Helps breaking up and distributing of capsule contents in the GIT - Recall: dissolution is the limiting step of oral absorption drug - pregelatinized starch, croscarmellose, sodium starch glycolate

Empty Hard Gelatin Caps

- Made of gelatin, sugar, water - Can be clear, colorless, tasteless - Can be colored - Can be opaque by using agents like Titanium Dioxide

Hard Gelatin Capsule (HGC) can be used in

- Most commercial capsules - Blinded clinical studies - Extemporaneous compounding

Preparation of SGC

- Plate process - Rotary or reciprocating die process: + SGC are produced, filled, and sealed in a continuous operation + Most SGCs are prep this way + Ribbon of gelatin are formed and used to encapsulate the fill

What is Gelatin made of?

- Product of the partial hydrolysis of collagen, obtained from the skin, white connective tissue, and bones of animals

Disintegration Test

- Same procedure as for uncoated tablets - Repeated immersion in a particular fluid at 37C should yield a soft mass, having no palpably firm core and only some fragments of the capsule shell

Opening capsule

- Should be done only after conferring with a pharmacist. - Absorption characteristics of the drug may be altered - Make sure it's NOT ER, DR

Gelatin Characteristics

- Stable in air when dry - Subject to microbial decomposition when moist - HGCs normally contain 13-16% moisture

Moisture permeation test (USP required)

- Tests the degree and rate of moisture penetration into a unit dose package - Capsule is packaged along with a color-revealing desiccant pellets - Package is exposed to a known relative humidity over time and the desiccant pellet is observed for color change - Pre-test and post-test weight of the package is also recorded.

Hermetic seal

- The quality of something being airtight (excluding passage of air, oxygen, or other gases)

Content uniformity

- Unless otherwise stated in the USP monograph for an individual capsule - For 9 out of 10 capsule, the amount of API MUST be within the range of 85-115% of the label claim - 1 out of 10 capsule can be from 76-125% of the label claim

How to prevent capsules from absorbing extra moisture?

- Use Desiccant materials - Silica gel, clay, activated charcoal

What are the advantages of SGC?

- Used to hermetically seal liquids, suspension, pasty materials, dry powder, even pre-formed tablets - Easily swallow - Pharmaceutically elegant

Liquid that may be encapsulated into SGCs

- Water-immiscible volatile and nonvolatile liquids - Water-miscible nonvolatile liquids - Water-miscible and relative nonvolatile compounds

Compendial requirements of capsule

- concise compilation of a body of knowledge (usually a book-USP), which is a compendium of drug information - Substance added to capsules, to enhance their ability, usefulness, or elegance or to facilitate their manufacture - Containers: USP listed container specifications

Soft Gelatin Capsules (SGC)

- made of gelatin, glycerin/polyhydric alcohol like sorbitol - has more moisture than HGC - may contain preservative (methylparaben, propylparaben) - May contain opaquants - Oblong, oval, round, single-colored, 2-toned, imprints

Diluent/Filler

- may be added to the drug formulation to produce the proper capsule fill volume - Lactose, microcrystalline cellulose, starch - provide bulk, (may) cohesion (uniform blend of drug formulation + filler) of the powders

Unit dose packaging

- useful for pharmacies serving nursing homes and hospital - Provides sanitary handling of meds - Ease of identification - Security and accountability

How to achieve uniform distribution of the drug among the contents of a capsule?

By having the similar density and particle size of the drug and non-drug components

Which is incorrect regarding HGC? A. The capsule cap is shorter than the body B. The 2 parts of the capsule are secured by locking rings C. Perfectly engineered one-pieced gelatin capsule D. Once closed, the capsule is leak-free

C. HGC is 2 pieced

Storage of capsules

capsules should be stored in a tightly capped container in a cool, dry, place

True/False Most commercial capsules are colorless, and clear

False Most commercial capsules contain colorants + opaquants to make them look distinctive, sometimes caps and bodies are different colors

Desiccant may be used to?

Protect hygroscopic agents

Stability testing

Specific tests conducted to determine the stability of the API molecule and the influence of environmental factors such as: - Temp - Light - Humidity - Formulative components - Container and closure system (Used to determine shell life)

True/False Most capsules are considered immediate release

True - Capsule immediately begins to dissolve in the GI tracy unless deliberate effort has been made to modify the release

HGC Developing the Formulation

Use of the smallest capsule size that is properly filled is preferred

Dissolution test

Uses the same apparatus, dissolution medium, and test as that for uncoated and plain-coated tablets

Manufacture of HGC

1. Pin or pegs are dipped into a gelatin mixture with desired shape, diameter, depth 2. Pins or pegs left in place to achieve proper length and thickness of coating 3. Lift up and let dry 4. Trim to get proper length, and remove cap from pin/pegs 5. Thickness of the gelatin wall is strictly controlled so cap and body can fit perfectly 6. Colorant/opaquant add to gelatin bath 7. Shape, color, imprint can be different

Weight variation

HGC: 10 intact capsules are individually weighed, then content removed and emptied shells are individually weighed. (net weight= shell weight + content) SGC: Same concept but solvent is used to remove content from shell and it should evaporate at room temp

Solid Dosage Forms

Medicinal agents or inert substances (placebo) are enclosed in a small shell of gelatin