Powders and Granules

Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D

Department of PharmaceuticsFaculty of Pharmacy

Omer Al-Mukhtar UniversityTobruk, Libya.

E-mail: nanjwadebk@gmail.com

2014/06/08 1Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

CONTENTS

1. Definition, advantages, size shape, storage.

2. Hard gelatin capsules (shell manufacture filling).

3. Soft gelatin capsules (manufacturing and filling).

4. Sustained release and enteric coated capsules.

5. Formulation factors affecting bioavailability.

6. Microencapsulation (Introduction, advantages).

7. Coacervation phase separation technique.

8. Pan coating, electrostatic deposition, spry drying.

9. References.2014/06/08 2Faculty of Pharmacy, Omer Al-Mukhtar University,

Tobruk, Libya.

Definition of Powders

• A pharmaceutical powder is a mixture of finely divided drug and/or chemicals in dry form.

• Powders are solid dosage form of medicament which are meant for internal and external use.

• They are available in crystalline or amorphous form.

• The particle size of powder plays an important role in physical, chemical and biological properties of the dosage forms.

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Definition of Granules

• Granulation is the process in which primary powder particles are made to adhere to form larger, multiparticle entities called granules.

• Pharmaceutical granules typically have a size range between 0.2 and 0.4 mm, depending on their subsequent use.

• In the majority of cases this will be in the production of tablets or capsules, when granules will be made as an intermediate product and have a typical size range between 0.2 and 0.5 mm.

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Advantages of Powders and Granules

• Solid preparations are more chemically stable than liquid ones.

• Powders and granules are a convenient form in which to dispense drugs with a large dose.

• Orally administered powders and granules of soluble medicaments have a faster dissolution rate than tablets or capsules, as these must first disintegrate before the drug dissolves.

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Particle Size Powders and Granules

• Particle size is characterized using these terms :

i. Very coarse (#8)

ii. Coarse (#20)

iii. Moderately coarse (#40)

iv. Fine (#60)

v. Very fine (#80)

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Particle Shape Powders and Granules

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Different shapes of crystals

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Hard gelatin capsules (shell manufacture filling)

• These are used for administration of solid medicaments.

• The capsule shell is prepared from gelatin, colour and titanium dioxide to make it opaque.

• It consists of two parts i.e. body and cap.

• The powdered material is filled into the cylindrical body of the capsule and then the cap is placed over it.

• The empty capsules are available in various sizes.

• They are numbered according to the capacity of the capsules.

• The number starts from 000 and goes up to 5.2014/06/08 9Faculty of Pharmacy, Omer Al-Mukhtar University,

Tobruk, Libya.

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Capsule number Approximate capacity in mg

000 950

00 650

0 450

1 300

2 250

3 200

4 150

5 100

Hard gelatin capsules (shell manufacture filling)

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Hard gelatin capsules (shell manufacture filling)

• The capsules can be filled either by hand or by a semi-automatic device or by an automatic filling machine.

• Capsule filling machine (Hand operated) It consists of:-

1. A bed having 200-300 holes

2. A loading tray having 200-300 holes

3. A powder tray

4. A pin plate having 200-300 pins

5. A sealing plate having a rubber top

6. A lever

7. A cam handle

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Methods of filling the hard gelatin capsules

Soft gelatin capsules (manufacturing and filling)

• These are used for administration of liquid medicaments. Soft gelatin capsules are available in round, oval and tube like shapes.

• They are made from gelatin. The gelatin is plasticized by the addition of glycerin and sorbitol etc.

• The soft gelatin shell may contain a preservative to prevent the growth of fungi.

• They are used to enclose liquid medicaments-oils, suspensions, food concentrates and ophthalmic products.

2014/06/08 13Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

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Soft gelatin capsules (manufacturing and filling)

• Soft gelatin capsules are generally filled mechanically.

• The manufacturing of the capsule shell and the filling of the medicament take place simultaneously. Nowadays, a rotary machine is used for this purpose.

• Rotary die machine, the soft gelatin capsules are prepared and then filled immediately with the liquid medicaments.

• The machine consists of two hoppers.

• Liquid gelatin mixture is placed in one hopper and the liquid medicament in the other hopper.

• There are two rotating dies which rotate in opposite directions.

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Method of filling of soft gelatin capsules

Sustained release capsules

• In order to maintain a proper blood concentration of the medicament and reducing the number of doses per day, a capsule, containing numerous coated pellets, is administered that release the drug successively over a long period.

• The finely powdered drug is first converted into pellets.

• These pellets are treated with protective coatings that delay the release of the drug.

• The batches of pellets are mixed thoroughly and suitable doses are filled into capsules.

2014/06/08 16Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

Enteric coated capsules

• These capsules do not disintegrate in the stomach (acid medium) but break-up in the intestine (alkaline medium).

• A special type of treatment or coating is given to the capsules so that these can pass unchanged through the stomach but get disintegrated in the intestine.

• On a commercial scale, a coating of cellacephate (cellulose acetate phthalate) and mixtures of waxes with fatty acids or their esters is given.

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• The following categories of drugs need enteric coatings.

1. Drugs which cause irritation to the gastric mucosa and lead to nausea and vomiting.

2. Drugs which are destroyed by the gastric juices.

3. Drugs which are specially intended to act in the intestine e.g. amoebicides and anthelminitics.

4. Drugs which are required to produce a delayed action.

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Enteric coated capsules

Formulation factors affecting bioavailability

• The types of dosage form and its method of preparation or manufacture can influence bioavailability.

• Particular drug is incorporated and administered in the form of a solution, a suspension or solid dosage form can influence its rate and/or extent of absorption from the gastrointestinal tract.

• The type of oral dosage form will influence the number of possible intervening steps between administration and the appearance of dissolved drug in the gastrointestinal fluids.

• Types of dosage form: aqueous solution > aqueous suspensions > solid dosage forms (e.g. hard gelatin capsules or tablets).

2014/06/08 19Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

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Formulation factors affecting bioavailability

Microencapsulation (Introduction)

• Microencapsulation is a process or technique by which thin coating can be applied to small particles of solids, droplets of liquids or dispersion, thus forming microcapsules.

• The microcapsules may consist of a single particle or clusters of particles.

• It differs from other coating methods because microencapsulation process is used to coat the particles having a particle size range from several tenths of a micro to 5000 .

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• Advantages of Microencapsulation Process

1. It is used for masking the taste of bitter drugs.

2. It is used for preparing prolonged action dosage form

3. It is used in modifying the physical characters of a material required in certain formulations

4. The technique is used to separate an incompatible material

5. It is used to protect chemicals against moisture and oxidation.

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Microencapsulation (advantages)

Coacervation phase separation technique

• Coacervation means the separation of a liquid or phase when solution of two hydrophilic colloids are mixed under suitable conditions.

• In this method, the three immiscible phases of core material, solvent and coating material are formed followed by deposition of coating material on the core.

• The coating material is dissolved in a suitable solvent and the core material is uniformly dispersed in the solution of the coating material.

• Then the coating material is phased out of its solution which starts getting deposited on the particles of the core material.

2014/06/08 23Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

Pan coating

• In this technique the coating is done in a pan made up of copper or stainless steel.

• The pan is rotated with the help of an electric motor.

• The tablets to be coated are placed in the pan.

• Hot air is blown in, speed of the pan is adjusted in such a way that the tablet remain separated from each other in the pan.

• After coating, polishing is done in a polishing pan, pan coating technique is used for sugar coating, film coating and enteric coating.

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Pan coating

Electrostatic deposition

• The method is useful both for solid particles and liquid droplets.

• In this process, the core and coating materials are electrically charged by means of high voltage such as 10, 000 volts etc.

• The core is charged and placed in the coating chamber.

• The coating material is also charged before it is sprayed as a mist.

• Because the charges are of opposite kind, the coating material gets deposited on the core due to electrostatic attraction.

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Spry drying• The spray drying provides a large surface area for heat

and mass transfer by atomizing the liquid to small droplets.

• Sprayed into a stream of hot air, so that each droplet dries to an individual solid particle.

• Spry drying ensures good air circulation, facilitates heat and mass transfer and encourages the separation of dried particles from the moving air by the centrifugal action.

• The character of the particles is controlled by the droplet size, and so the type of atomizer is important.

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Spry drying

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THANK YOUe-mail: nanjwadebk@gmail.com

2014/06/08 29Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.