Gelatin Capsules and Manufacturing Processes

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Questions and Answers

What is the primary advantage of capsules over compressed tablets?

They are cheaper to produce.

They are available in larger doses.

They can completely mask unpleasant odours & tastes. (correct)

They have a longer shelf life.

What does the term 'capsula' mean in Latin?

Little case

Small box (correct)

Container

Medicine holder

What type of hydrolysis is used to produce Type A gelatine?

Acid hydrolysis (correct)

Thermal hydrolysis

Enzymatic hydrolysis

Basic hydrolysis

What is a primary raw material used for making gelatine capsules?

Animal bones and skins Signup and view all the answers

Which of the following is not a characteristic of gelatine?

Highly absorbent Signup and view all the answers

Which plasticizer is most frequently used in hard gelatine capsules?

Glycerol Signup and view all the answers

What is an essential factor in maintaining the quality of hard capsules?

Avoiding excessive humidity or dryness Signup and view all the answers

What is a common use for titanium dioxide in capsule manufacturing?

As an opacifying agent Signup and view all the answers

What is the primary reason for the shift from soluble dyes to pigments in capsule manufacturing?

Pigments, particularly iron oxides, are preferred. Signup and view all the answers

Which of the following is NOT a basic requirement for formulations to be filled into capsules?

Should dissolve easily in water. Signup and view all the answers

What is one method to separate incompatible drugs within capsules?

Insert a coated tablet of one ingredient into a capsule containing the other. Signup and view all the answers

How are hard capsule shells primarily manufactured?

By mechanical dipping pegs into melted gelatine. Signup and view all the answers

Which technique is used for locking and sealing capsules to prevent accidental separation?

A narrow band of gelatine. Signup and view all the answers

What is the main purpose of adding preservatives during capsule manufacture?

Prevent microbiological contamination. Signup and view all the answers

Which of the following is true regarding the capacity of hard gelatine capsules?

Capacity can vary according to density and compressibility. Signup and view all the answers

Which method is NOT used to fill hard gelatine capsules?

Directly pouring powder. Signup and view all the answers

What is the primary function of the metering pump in the rotary die process?

To inject the fill under pressure into the gelatine Signup and view all the answers

Why are seamless gelatine capsules preferred over traditional sealed capsules?

They do not rely on the sealing of gelatine sheets Signup and view all the answers

Which of the following is NOT an advantage of sustained release medication?

Increased frequency of administration Signup and view all the answers

What factor does NOT influence the release of a drug from its coating?

Molecular weight of the drug Signup and view all the answers

What characterizes sustained release dosage forms?

They aim to match the rate of drug release to its elimination Signup and view all the answers

Which material is commonly used for enteric coating of capsules?

Cellulose acetate phthalate Signup and view all the answers

Why is it important to avoid rapid dissolution of a complex in the stomach?

It can cause irritation to the gastric mucosa Signup and view all the answers

What method is used to coat drug-coated beads in sustained release capsules?

Pan coating with a non-aqueous solution Signup and view all the answers

What role does pH play in the disintegration of the coating material?

It triggers the disintegration of the coating Signup and view all the answers

What role does cold liquid paraffin serve in the seamless gelatine capsule process?

It helps congeal the gelatine without dissolving it Signup and view all the answers

Which of the following describes a reason for using enteric-coated capsules?

To protect the drug from gastric fluids Signup and view all the answers

What does the dissolution rate of a drug from capsules depend on?

The rate of penetration of dissolution medium Signup and view all the answers

How much of the drug-coated beads provides the initial release of medication in a spansule?

Approximately 1/4 of the beads Signup and view all the answers

What material is formed by reacting a drug with tannic acid?

Insoluble complex Signup and view all the answers

What is a potential advantage of using a 10% solution of cellulose acetate phthalate for coating?

It avoids the use of heat Signup and view all the answers

What is the role of disintegrants in drug formulations?

To promote the breakdown of the powder mass without affecting solubility. Signup and view all the answers

Which factor does NOT affect the dissolution rate of a drug?

Route of administration Signup and view all the answers

Which component is often used as a diluent in pharmaceutical formulations?

Avicel (microcrystalline cellulose) Signup and view all the answers

What characteristic of a drug significantly impacts its bioavailability in soft gelatine capsules?

Particle size of the drug Signup and view all the answers

What is the purpose of lubricants in powder mixtures for capsules?

To improve the handling and filling properties of the powder mixture. Signup and view all the answers

Which of the following statements about weight variation in capsules is true?

Weight variation is not a reliable method for assessing dosage uniformity. Signup and view all the answers

Why is it important to include a wetting agent in a capsule formulation?

To increase the dissolution by enhancing wettability. Signup and view all the answers

Which property of a drug does NOT influence its solubility in a vehicle?

Visual appearance of the drug Signup and view all the answers

What is the method used to calculate the net weight of the contents of emptied shells?

Subtracting the weight of the shell from the gross weight. Signup and view all the answers

How is content uniformity determined for the capsules?

By ensuring all capsules are within 85% to 115% of the average specified potency. Signup and view all the answers

What does the disintegration test require for the capsules?

Capsules must break into a soft mass with no firm core. Signup and view all the answers

During the dissolution test, what should be done if a capsule floats on the surface of the dissolution fluid?

Attach a piece of nonreactive material to the capsule. Signup and view all the answers

How many capsules are initially assayed in the official content uniformity test?

10 capsules. Signup and view all the answers

Which statement accurately describes the outcome if more than 1 but less than 3 capsules fall outside the specified limits?

The remaining 20 capsules must be assayed individually. Signup and view all the answers

What is the maximum allowable percentage a capsule can fall below in the content uniformity test?

75% Signup and view all the answers

What is a requirement for the dissolution medium used in the dissolution test?

It must contain at least 900 ml of fluid. Signup and view all the answers

Study Notes

Capsules

Capsules are a small box, the second most popular oral dosage form.
Capsule administration can involve swallowing whole or opening and sprinkling contents on food.
Capsules have advantages over tablets, including elegance, ease of swallowing, and the ability to mask odors and tastes.
Capsules can be made opaque, which is beneficial for photosensitive drugs.

Types of Capsules

Hard gelatin capsules consist of two pieces (cap and body) that fit together. They are manufactured and filled separately.
Soft gelatin capsules are manufactured and filled in a single operation.

Raw Materials for Gelatin Capsules

Raw materials for hard and soft capsules are similar.
Gelatin is the main component, a good film-forming material.
Gelatin undergoes a reversible phase change from solution to gel at temperatures close to ambient.
It's readily soluble in biological fluids at body temperature and non-toxic.
Animal bones and skins are the raw materials for gelatin, prepared through collagen hydrolysis.
Two types of gelatin exist: Type A (acid hydrolysis) and Type B (basic hydrolysis).

Plasticizers

Hard gelatin capsules have less plasticizer than soft gelatin capsules.
Common plasticizers include glycerol, sorbitol, propylene glycol, sucrose, and acacia.

Colorants

Soluble dyes (mainly synthetic) or insoluble pigments (like titanium dioxide and iron oxides) can be used as colorants.
There's a trend towards using insoluble pigments, particularly iron oxides, instead of soluble dyes.

Preservatives

Preservatives are sometimes added to prevent microbiological contamination during manufacturing.

Hard Gelatin Capsules (Details)

Available in sizes 000 to 5 (000 is largest, 5 is smallest).
Capacity varies according to the density and compressibility of the powder filling.
Used for powder, granules, tablets, pellets, beads, semi-solids, and thermo-softening materials.

Basic Requirements for Capsule Fillings

Dosage needs to be accurate.
Active ingredients should release in a usable form to the patient.
The filling should not react with gelatin (e.g., avoid aldehydes).
The filling shouldn't interfere with the capsule shell (e.g., water softening).
Incompatible ingredients within the same capsule can be separated by coating one ingredient or placing the substances in separate small capsules inside a larger one.

Locking and Sealing of Capsules

Techniques include using a narrow band of gelatin, spot welding with a hot probe, segmented raised collars, and moistening the caps' inner surface with water.

Filling of Hard Gelatin Capsules

Filling can be hand-operated or involve various forms of semi-automatic or fully-automatic machines that handle removal, filling, replacement and ejection of filled capsules.

Soft Gelatin Capsules (Differences)

Soft gelatin capsules can hold solids, liquids, and semi-solids.
Gelatin, colorants, and plasticizers can be used.
Soft gelatin capsules are more flexible than hard ones.
Soft gelatin capsules are filled and sealed in a single step.

Composition of Soft Gelatin Capsules

Sugar is replaced with plasticizers to impart elasticity.
These can contain up to 5% sugar, mainly for chewable properties.
Formulations include spheres (pearls) and globules with capacities ranging from 1 to 480 minims.
The filling materials include combinations of liquids, solutions, suspensions, semi-solids, or dry powders; only substances that don't dissolve gelatin should be used (like oils).

Manufacture Methods

Plate method (small scale): involves placing gelatin sheet over a die plate with pockets, drawing the sheet into the pockets with vacuum, filling the pockets, placing another sheet on top, and using machine pressure to form and cut out the capsules.
Rotary die process (Scherer): uses rotary drums to spread gelatin solution into sheets, which are fed between rotary dies. This process heats the gelatin and seals/cuts the capsules from the sheets in a continuous operation.

Seamless Gelatin Capsules

Not sealed by pressure from two gelatin sheets.
Cold liquid paraffin (4°C) is used because it's non-solvent and solidifies gelatin.

Sustained Released Capsules

More efficient drug utilization.
Reduced total drug intake.
More convenient administration.
Dosage forms have immediate- and sustained-release portions, controlling drug release rate equal to its elimination/detox rate.
Suitable uses include chronic conditions, but not for rapidly-acting antibiotics or muscle relaxants.

Sustained Released Dosage Forms

Hard gelatin capsules, medicated and pan-coated onto sugar starch beads, releasing medication initially.
Remaining beads are coated with fatty/waxy substances (beeswax, glyceryl monostearate, ethyl cellulose).
Drug release depends on moisture penetration into the fatty/waxy coat.
Sustained release portions are coated with styrene-maleic acid copolymers.
Drug release is based on pH sensitivity (disintegrating at intestinal pH) and stomach emptying rate.
Cationic drugs can be absorbed onto cationic exchange resins, affecting release rates.

Enteric Coated Capsules

Capsules resist gastric dissolution, releasing contents in the intestine for uses like when a drug is inactive/irritating in stomach or needs high intestinal concentration.
Coating materials include shellac, cellulose acetate phthalate, fatty/waxy materials and formaldehyde treatment to harden gelatin and form methylene bridges.
Coating is done by a method that uses cellulose acetate phthalate solution to coat capsules for a minute and drying on gauze.

Dissolution Rate of Drugs from Capsules

Affected by shell dissolution rate, the medium penetration rate into the powder, rate of powder aggregation, and the primary particle's nature.
Dissolution is the rate-determining step in absorption influencing the drug's availability for absorption in the gastrointestinal fluid.

Formulation Factors Affecting Drug Availability

Active ingredients: physicochemical properties (solubility, melting point, crystalline form) affect solution rate proportionally to surface area. Smaller particles have larger surface areas.
Additives:
Diluents: inert materials increasing mixture volume, choice based on active ingredient's solubility and proportion. Common diluents include lactose, dicalcium phosphate, and microcrystalline cellulose.
Disintegrants: help break up the powder efficiently without affecting solubility of active ingredients (starch grains).
Lubricants/Glidants: improve filling properties and sometimes affect drug release. Magnesium stearate is a common example.
Surfactants/Wetting agents: increase powder wettability, commonly used to overcome the hydrophobic effect of magnesium stearate.

Factors Affecting Bioavailability in Soft Gelatin Capsules

Solubility: Acid-soluble drugs dissolve quickly in the stomach, leading to quicker distribution.
Particle size: Smaller particles have higher surface areas and faster dissolution rates.
Vehicle: hydrophilic (water-loving) or hydrophobic (water-fearing) vehicles are used based on the drug's nature.
Suspending agents: Increase bioavailability of insoluble drugs.

Evaluation of Commercial Capsules

Weight variation method involves weighing 10 capsules, removing contents, and reweighing each part and the whole to calculate the net weight of the contents and the degree of accuracy in the content of each dose.
Content uniformity ensures consistent drug amounts per capsule in a batch.
It calculates whether a batch of capsules is of the correct strength.
Dissolution test measures how quickly a drug is released from the capsule shell in a specified medium.

Moisture Permeation Test

The test is used to determine how much water or moisture permeates the packaging a dosage unit
Assess moisture absorption over time.

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Test your knowledge of gelatin capsules and their manufacturing processes with this quiz. Explore topics such as the advantages of capsules over tablets, materials used in capsule production, and techniques for ensuring capsule quality. Perfect for students and professionals in pharmaceutical sciences.