SPHERONIZATION

Semin

arOn

V.VishalaM.Pharm Industrial Pharmacy (1st Sem)

St.PETER’S INSTITUTE OF PHARMACEUTICAL SCIENCES

VIDYA NAGAR, HANAMKONDA.WARANGAL 506001

CONTENTS INTRODUCTION

ADVANTAGES OF SPHERONIZATION

EXTRUSION SPHERONISATION

MELT SPHERONIZATION

FACTORS AFFECTING SPHERONIZATION

APPLICATIONS

CONCLUSION

REFERENCES

INTRODUCTION

WHAT IS SPHERONIZATION?

Definition of Spheronization:

•Spheronization, or Maramuerization, is a rapid and flexible process where pharmaceutical products are made into small spheres, or spheroids. (or)•The formation of small spheres of material.

•Spheronized products are relatively dense, of a uniform in size and shapeand have defined surface characteristics.

Why spheronization?

The flow characteristics of spheres makes them suitable for transportation in the pharmaceutical industry.

Spheres provide the lowest surface area to volume ratio and thus pharmaceutical compounds can be coated with a minimum of coating material.

Advantages of Spheronization

Spheronization offers

Optimum flow and handling characteristics More reproducible packing into small containersMinimum surface area/volume ratioOptimum shape for coating and controlled releaseEasy mixing of non compatible productsElimination of dustImproved hardness and friabilityImproved packing of beds and columns

EXTRUSION-SPHERONIZATION

Extrusion–Spheronization is a multistep process involving dry mixing, wet granulation, extrusion, Spheronization, drying and screening, coating.

Variety of extruders: Screw-fed extruders, Gravity-fed extruders, and Ram extruders

Variety of extrudersSCREW FED EXTRUDERS

GRAVITY FED EXTRUDER

RAM EXTRUDER

Screw-fed extruder: The screw rotates along the horizontal axis and hence transports the material horizontally;

They may be of two types:1.Axial screw extruders, 2.Radial screw extruders.

1.Axial extruders: These have a die plate that is positioned axially, consist of a feeding zone, a compression zone, and an extrusion zone.

2.Radial extruders: The transport zone is short, and the material is extruded radially through screens mounted around the horizontal axis of the screws.

(A)Axial extruder

Screw-fed Extruders:

(B)Radial screw extruder

Gravity-fed Extruders:

(A)Rotary-cylinder extruder (B) Rotary-gear extruder

Gravity-fed extruders: These are of two types , which differ primarily in the design of the two counter-rotating cylinders. 1.The Rotary Cylinder and2. Rotary Gear Extruders

1.Rotary Cylinder Extruder: One of the two counter-rotating cylinders is hollow and perforated, whereas the other cylinder is solid and acts as a pressure roller.

2.Rotary-Gear Extruder: There are two hollow counter-rotating gear cylinders with counterbored holes.

Ram Extruders:

1.The ram extruder is probably the oldest type of extruders; a piston displaces and forces the material through a die at the end.

2. These extruders are preferentially used in the development phase, because they can also measure the rheological properties of formulations.

Ram Extruder

Principle of Spheronization processIn principle the basic

machine consists of a rotating friction disk, which spins at high speed at the bottom of a cylindrical bowl.

The spinning friction disc has a carefully designed groove pattern on the processing surface. This is most often crosshatched, but several sizes and other types are available

Extrudates are fall on the spinning disc. and cut into segments with a length ranging from 1 to 1.2 times the diameter.

These segments then collide with the bowl wall and they are thrown back to the inside of the friction plate.

Centrifugal force sends the material to the outside of the disc.

These cylindrical segments are gradually rounded by the collisions with the bowl wall, the plate and each other

The continuous collision of the particles with the wall and with the friction plate gradually turn the cylindrical segments into spheres,

When the particles have obtained the desired spherical shape, the discharge valve of the chamber is opened and the granules are discharged by the centrifugal force.

The design principle of the spheronizer is relatively simple but additions and adaptations are available. For example, the Caleva "Twin" incorporates two spheronizers which allow continuous productions of spheroids.

CYLINDRICAL EXTRUDATE CYLINDRICAL RODS

CYLINDERS WITHROUNDED ENDS

DUMBBELLS

ELLIPSOIDS

SPHEROIDS

Shape transitions during a Spheronization process

In an extrusion–spheronization process, formulation components such as fillers, lubricants, and pH modifiers play a critical role in producing pellets with the desired attributes.

Lubricants: Water and other Granulating media. Role: Lubricants are sometimes incorporated to improve processing.

Fillers: Microcrystalline cellulose and lactose. Role: Regulating the water content and distribution in the granulation. In effect, it modifies the rheological properties of the formulation and imparts plasticity to the pellets.

pH modifiers: Organic acids Role: Stabilize sensitive drug substances or modify the release characteristics, especially the solubility of the drug substance.

MELT SPHERONIZATION

Melt Spheronization is a process whereby a drug substance and excipients are converted into a molten or semi molten state and subsequently shaped using appropriate equipment to provide solid spheres or pellets.

The drug substance is first blended with the appropriate pharmaceutical excipients, such as polymers and waxes, and extruded at a predetermined temperature.

The extrusion temperature must be high enough to melt at least one or more of the formulation components. The extrudate is cut into uniform cylindrical segments with a cutter.

The segments are spheronized in a jacketed Spheronizer to generate uniformly sized pellets.

Factors Effecting SpheronizationDisc speed and loadDisc groove geometryDisc diameter and speedRetention timeProduct parametersOther factors

MELT SPHERONIZATION

Melt Spheronization is a process whereby a drug substance and excipients are converted into a molten or semi molten state and subsequently shaped using appropriate equipment to provide solid spheres or pellets.

The drug substance is first blended with the appropriate pharmaceutical excipients, such as polymers and waxes, and extruded at a predetermined temperature.

The extrusion temperature must be high enough to melt at least one or more of the formulation components. The extrudate is cut into uniform cylindrical segments with a cutter.

The segments are spheronized in a jacketed Spheronizer to generate uniformly sized pellets.

ApplicationsControlled release pellets for encapsulationDelayed release enteric coated pelletsSustained release pelletsMulti particulate systemMulti unit erosion matrix pelletsPellets for special tabletting applicationsImmediate release pellets for sachets

Conclusion Today spheronization (wet mass extrusion) and

melt extrusion spheronization represents an efficient pathway for novel drug delivery system. The potential of this technology is lies in the scope for different oral controlled delivery systems including oral and topical delivery systems. Because of its simple design, high efficiency of producing spheres and fast processing, extrusion spheronization has found a special position in pharmaceutical industry and especially in case of production of multiparticulate oral controlled release dosage forms. Pellet formation by this technique produces more spherical pellets and offers more advantages than other pelletization process.

REFERENCES:1. Special Delivery: Advances in Drug Therapy. The Research News;

University of Michigan, 1986; 1.2. Fielden, K.E.; Newton, J.M.; Rowe, R.C. A Comparison of the Extrusion

and Spheronization Behavior of Wet Powder Masses Processed by a Ram Extruder and a Cylinder Extruder. Int. J. Pharm. 1992, 81, 225–233.

3. Fielden, K.E.; Newton, J.M.; Rowe, R.C. The Effect of Lactose Particle Size on the Extrusion Properties of Microcrystalline Cellulose-Lactose Mixtures. J. Pharm. Pharmacol. 1989, 41, 217–221

4. L. Lachman, H.A. Lieberman, J.L. Kanig (1986). The Theory and Practice of Industrial Pharmacy (Third ed.). Lea & Febiger, Philadelphia. ISBN 0-8121-0977-5.

5. James Swarbick. Encyclopedia of PHARMACEUTICAL TECHNOLOGY Third Edition VOLUME 1. ISBN 0‑8493‑9396‑5.

6. Extrusion-spheronisation - A literature review.,Chris Vervaet, Lieven Baert and Jean Paul Remon. International Journal of Pharmaceutics; Volume 116, Issue 2, 28 March 1995, Pages 131-146

Marumerizer:It consists of a two parts:1.Static cylinder or stator and2.Rotating friction plate.

A typical friction plate has a crosshatch pattern, where the grooves intersect at a 900 angle. The rotational speed of the friction plate is variable and ranges from 100 to 2000 rpm; depending on the diameter of the unit.

Spheronizer friction plate with a cross-hatch pattern.