WELCOME

Presented by:Mr. Birudev Kale M. Pharm. ( Sem. II)

Under the guidance of Dr. N. H. Aloorkar H.O.D., Pharmaceutics.

RECENT ADVANCES IN PARTICLE ENGINEERING FOR

PHARMACEUTICAL APLLICATIONS

Particle engineering techniques

Sonocrystallisation

Cryogenic technologiesSupercritical

fluid technologySpray dryingSummaryReferences

CONTENTS

Introduction

INTRODUCTION

Particle engineering is a term coined to encompass means of producing

particles having a defined morphology, particle size distribution, and

composition.

In a stricter sense, particle engineering is associated with particle size

manipulation techniques.

Particle Engineering is a young discipline that combines elements of

microbiology, chemistry, formulation science, colloid and interface science,

heat and mass transfer, solid state physics, aerosol and powder science and

nanotechnology.

Particle engineering techniques are tools to modify the physicochemical,

micromeritic and biopharmaceutical properties of the drug.

PARTICLE ENGINEERING TECHNIQUESPARTICLE ENGINEERING TECHNIQUESPARTICLE ENGINEERING TECHNIQUES

•SUPERCRITICAL FLUID TECHNOLOGY

•CRYOGENIC TECHNOLOGIES

•SONOCRYSTALLISATION

•SPRAY DRYING

SUPERCRITICAL FLUID TECHNOLOGY These SCF technologies use super critical fluids either as solvent or

antisolvent and/or dispersing fluid.

Supercritical fluid (SCF)

Super critical status- Gases or liquids, which are when used under pressure

and temperature above the critical point, reach an aggregate state, which is

called Super Critical Fluid (SCF) state.

At the critical point only a single phase exist which has some properties

typical of liquids (density) and some of gases (viscosity, compressibility etc).

SCFs offer liquid-like densities, gas-like viscosities, gas-like

compressibility properties and higher diffusivities than liquids.

Contd…..

Super critical fluid technologies include

1.Rapid expansion of supercritical solutions (RESS)

2.Precipitation with compressed fluid anti solvents (PCA)/(GAS)/(SAS).

3.Particles from gas saturated solutions (PGSS)

4.Supercritical (fluid) assisted atomization (SAA)

5.Supercritical fluid extraction of emulsion (SFEE)

Rapid expansion of supercritical solution (RESS)1.Particle range-20 to 200 nm

Flow sheet of a typical RESS process

Precipitation with compressed fluid anti solvents (PCA)2.

3. Particles from gas saturated solutions (PGSS)

Size ranging between 1- 42 µm

4. Supercritical fluid assisted atomization (SAA)

5. Super critical fluid extraction of emulsion (SFEE)

CRYOGENIC TECHNOLOGIES Cryogenic technology uses cryogenic liquids. They are extremely cold, with boiling points below -51°C. Cryogens have high expansion ratios, which average ~700:1. When they are heated (i.e. exposed to room temperature), they vaporize (turn into a gas) very rapidly.

Cryogenic technologies include:1. Spray freezing into cryogenic fluids2. Spray freezing onto cryogenic fluids (SFL) 3. Spray freezing into vapour over liquid

(SFV/L)4. Ultra Rapid Freezing (URF)

Spray freezing into cryogenic fluid1.

Spray freezing onto cryogenic fluid2.

Invented by Briggs and Maxwell.

In this technique, the drug and the carrier (mannitol, maltose,

lactose, inositol or dextran) are dissolved in water and atomized

above the surface of agitated cryogenic fluid.

Sonication probe can be placed in the stirred refrigerant to

enhance the dispersion of the aqueous solution

Spray freezing into vapour over liquid3.

Freezing of drugs solution in cryogenic fluid vapours and

subsequent removal of frozen solvent produces fine drug particles

with high wettability.

During spray freezing into vapour over liquid, the atomized

droplets typically start to freeze in the vapour phase before they

contact the cryogenic liquid.

As the solvent freezes, the drug becomes supersaturated in the

unfrozen regions of the atomized droplet, so fine drug particles may

nucleate and grow.

Ultra rapid freezing4.

This technology involves the use of a solid cryogenic

substrate. A solution of the drug is applied to the solid

surface of the substrate, where instantaneous freezing

takes place. Brownian motion of the particles in solution

is slowed significantly, so reactive species have little time

to react before being frozen into the solid state. Removal

of the frozen particles and lyophilization of the solvent

produces drug particles.

Application of ultrasound energy to control the nucleation of a crystallization process.

SONOCRYSTALLISATION

Applying ultrasound to crystallization results in:

Nucleation at the lowest level of supersaturation

Narrow particle size distribution

Decrease in the level of cooling necessary to achieve crystallization

Highly predictable crystallization

Crystallization consists of two major events:1. Nucleation: Solute molecules gather into clusters & reach a critical size to

constitute nuclei2. Crystal growth: Subsequent growth of the nuclei

Contd…..

The ultrasound energy creates sequential compression then expansion.

Over several cycles, a bubble forms and grows then collapses. The

collapse of the bubble provides energy to encourage the nucleation

process at the earliest possible point in time. This results in highly

repeatable and predictable crystallization.

Working

It is possible to control the size and number of particles produced by the timing of the application

of the ultrasound to the super saturated solution.

Particle size control

Continuous ultrasound produces many nuclei resulting in small crystals

Initial ultrasound only produces finite nuclei which can be grown into large crystals

Pulsed ultrasound gives tailored crystal size

Contd…..

SPRAY DRYING

Particle size ranges from 5 -100 microns

A typical SD process consists of four steps:

(a) atomization of feed solution into a spray;

(b) spray-air contact involving flow and mixing;

(c) drying of sprayed droplets at elevated temperatures; and

(d) separation of dried product from the air.

The new frontiers in particle engineering are just opening up and it is likely that the particle engineering techniques will enhance the therapeutic applications of new and well established drug candidates.

SUMMARY

REFERENCES

1. Kumar A., Sahoo S. K., Padhee K., Kochar P. P. S., Satapathy A. and

Pathak N., Review On Solubility Enhancement Techniques For

Hydrophobic Drugs, Int. J. compr. Pharm., 2011, 3 (03).

2. Zijlstra G. S., Hinrichs L. J., Boer A. H., Frijlink H. W., “The Role of

Particle Engineering In Relation To Formulation And De-

agglomeration Principle In The Development of A Dry Powder

Formulation For Inhalation”, Eur. J. Pharm. Sci. (2004) 23, 139–149.

3. Derle D., Patel J., Yeole D., Patel A. and Pingle A.,

“Particle Engineering Techniques To Enhance Dissolution of Poorly

Water Soluble Drugs”, Int. J. Cur. Pharm. Res., 2010, 2, (1).

4. Vehring R., “Pharmaceutical Particle Engineering Via Spray Drying”, J.

Pharm. Res., May 2008, 25, (5).

5. Majerik V., Horvath G., Charbit G., Badens E., Szokonya L., Bosc N.,

Teillaud E., “Novel Particle Engineering Techniques In Drug Delivery:

Review of Coformulations Using Supercritical Fluids And Liquefied

Gases”, Hun. J. Ind. Chem., Veszprem, 2004, (32), 41-56.

6. Patel R. P., Patel M. P. and Suthar A. M., “Spray Drying Technology: An

Overview”, Ind. J. Sci. Tech., Oct 2009, 2 (10).

7. Rogers T. L., Hu J., Yu Z., Williams R. O., Johnston K. P., “A Novel

Particle Engineering Technology: Spray-freezing Into Liquid” Int. J.

P’ceutics , 2002, 93–100.

Contd……