Hi bloggers here comes my first of this month...Spherical crystallization
INTRODUCTION : Spherical crystallization is a particle design technique, by which crystallization and agglomeration can be carried out simultaneously in a single step. Spherical crystallization technique has emerged as one the areas of active research currently of interest in pharmaceutical manufacturing in recent times. It came into the forefront of interest due to the fact that crystal habit of a particular molecule can be modified during crystallization process as a result of which micrometric properties like flowability, packability, wettability and compressability of the powder drug are improved and moreover prepared spherical crystals can be compressed directly thereby bypassing several of the steps involved in wet and dry granulation.
METHODS OF SPHERICAL CRYSTALLIZATION:
The methods of spherical crystallization are categorized as:
1.Solvent Change Method (SC):
In this method the solution of the drug in a good solvent is poured into a poor solvent under controlled conditions of temperature and speed to obtain fine crystals. Bridging liquid assists the agglomeration of the crystals. The poor solvent has miscibility with good solvent but low solubility with solvent mixture so during agitation of the solvent system the crystals formed. This method is not suitaale for water soluable drugs.
2.Quasi Emulsion Solvent Diffusion Method (QESD):
In this method crystallization of drug occurs by counter diffusion of good solvent and poor solvent. It involves the formation of quasi- emulsion of solution of drug in good solvent with a non-solvent which there by finally solidifies resulting in the formation of crystals.
3.Ammonia Diffusion Method (AD):
In this method ammonia water acts as a good solvent as well as the bridging solvent. Other components of the system are bad solvent and hydrocarbon which reduces the miscibility of ammonia water with bad solvent. Droplets are formed by the fraction of ammonia water left as an immiscible phase and the counter diffusion results in movement of bad solvent into and ammonia out of the droplet resulting in the formation of agglomerates.
4.Salting Out Method (SO):
In this method crystallization occurs due to addition of suitable salt in presence of a bridging solvent.
The principle steps involved in the process of spherical crystallization:
1. Flocculation zone
2. Zero Growth zone
3. Fast Growth zone
4. Constant Size zone
- To improve the flowability and compressibility.
- For masking bitter taste of drug.
- To increase the solubility and dissolution rate of poorly soluble drug.
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