PRESENTATION ON DRY GRANULATION

PRESENTED BY GIRGIS ATTIA

INTRODUCTION

• Tablets as a dosage form are composed of active pharmaceutical ingredient (API/s) and non active pharmaceutical ingredients.

• These altogether are known as raw materials and are supplied in powdered form

• Mixing process is necessary is necessary to ensure that the API and other components are homogenously distributed through out the tablet

• Tablets are ultimately formed by pressure applied on the punches of a tablet press machine, filling of dies determine tablet weight and therefore the ability of granulation to fill freely into the die is important in ensuring a uniform fill, as well as continuous movement of the granulation from the feed hopper.

WHY GRANULATION

1) To improve the flow properties of a bulk powder mix: Because of their small size and or surface characteristics, many powders are cohesive (sticky) and do not flow well.

2) To prevent segregation of the ingredients in the mix

3) To improve compressability

4) To decrease environmental hazards for personnel from dust formation

5) To reduce material adherence when some powder components are hygroscopic

6) To decrease bulk volume and increase bulk density of powders

TYPES OF GRANULATION METHODS

• 1) WET GRANULATION:

• MIXING WET MASSING screening of granules drying lubrication compression

• 2) Dry granulation: no water or granulating fluid

• A) SLUGGING: original employed method

B) ROLLER COMPACTION

FACTORS INVOLVED IN SELECTION OF GRANULATION METHOD

• Typically selection of an appropriate granulation method is based on material properties of the proposed formulation, end requirements of the granules and obviously the tablet or capsule

• 1) stability under processing conditions: many active components are heat and or moisture sensitive, and under these circumstances Dry Granulation would be preferable.

• 2)moisture content: absence or low presence of moisture in dry processed materials allow the product to maintain a high level of drug stability over longer periods of time as chemical and/or microbial degradation are minimized.

• 3)Wet granules often lead to prolonged disintegration times, and thus the dry granulation process may be more suitable for simple immediate release tablet applications.

CONT.• 4) Logistics: Wet granulation processes tend to be expensive, labour intensive and time consuming.

It also require highly skilled operators and a high degree of processing control.

• 5)Dry granulation tend to produce adjustable and easy to manipulate grain size, bulk density, flowability and solubility of processed granules

• 6)Dry granulation process enhance solid dosage forms stability by increasing final tablet hardness and reducing tablet friability

• 7)Wet granulation tends to produce smooth spherical granules that possess good to excellent flowability characteristics

• 8) Dry granulation can be a continuous fully automated process with high throughput. Validation being required for the process as whole, whereas in wet granulation validation is required for each and every step.

• 9)introduction of stresses can adversely affect the API with dry granulation

HISTORY & DEVELOPMENT OF DRY GRANULATION

The process of slugging preceded the Roller compaction method, and this process can be described in the following way:

A) Initial granulation was forced down hoppers of big tablet processes that were fitted with large flat punches, about 1 inch in diameter.

B) These large slugs were subsequently broken down using oscillators or mills to form granules

ROLLER COMPACTION

• Dry roller compaction is the process of using mechanical pressure to compress fine powders into denser sheets. The basic concept of compaction is to force fine powders between two counter rotating rolls. As the volume decreases through the region of maximum pressure, the material is compressed into dense sticks or corrugated sheets. These sheets are then granulated through a milling system and series of screens to achieve the precise, uniform granule size specified.

Dry roller compaction is the best granulation process for materials sensitive to moisture and heat. Unlike wet granulation processes, which require liquid binders, alcohol solvents and high temperature drying, roller compaction is free of these additional ingredients and energy requirements. The end result is a higher quality, consistent granule—usually at a lower cost.

ADVANTAGES OF DRY GRANULATION• In addition to high quality and consistency, dry roller compaction produces granules that are:

•More durable, for improved crush strength.

• •Uniform, for more even downstream blending. Roll compaction produces consistent, irregular-shaped granules that "interlock" to reduce product stratification during shipping and handling.

• •Highly flowable powders compared to powders that bridge and cake. Tableting and other downstream processes are more efficient.

• •Sized specifically to meet your precise product requirements. Roller compaction offers control and range of granule size.

• •Dust free to prevent cross-contamination in the next stage of production. By converting your raw material to granule form, you greatly minimize dust that can cause health and production problems while decreasing maintenance costs.

• •Easily handled, transported and stored because of increased bulk density and flow properties.

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SLUGGING & DEVELOPMENT OF ROLLER COMPACTION• The slugging method had several drawbacks, such as damage to presses and tooling, frequent cleaning

and maintainence needed and oscillator screens were damaged breaking down the hard slugs.

• Hence Fitz-Patrick came up with the roller compaction machine L-83, which produced granules 75% faster than slugging. Less fines were produced and fines could be recycled for re-compaction.

• A further improvement was the larger Fitz-Patrick chilsonator L-89, but the mill employed in this machine had rapid rotating swing blades which tended to blow fines back up to nip area (area where powder was lodged and from which the chilsonate was produced) causing the rollers to jam and leading to powder loss. Also the L-89 had no suitable screening device for a single pass process, i.e. screening had to be done separately. The machine was difficult to clean and run clean. It also entailed a separate oscillation step with a second operator to break down the chilsonate into granules of the correct particle size

• After this came the vector roller compactor, which had a single feed screw, rollers were interchangeable. Alexanderwerk manufacturers came up with horizontally fed rollers and rollers were replaced by changing the entire head.

WORK OF ART

• The latest development in the field is the GERETIS roller compactor which came up with an ingenious idea of feeding the powder into the rollers through an angle of 30 degrees, which minimized powder loss. The previous slide features the GERETIS compactor

GRANULE CHARACTERISTICS

• Granules are coarse and rough in texture, and of low porosity and weaker than those from wet granulation. However, in my perspective and taking into account the above given advantages for the process, I do prefer the method and recommend it especially in the following situations:

• 1) API or excipient being sensitive to high temperatures as that used in the drying step for wet granules

• 2)API or excipient being sensitive to moisture

• 3) For low potency or high dose API, such as Aspirin or vitamins