**3. Result and discussion**

#### **3.1 Preparation of spherical crystals**

A typical spherical crystallization system involved a good solvent, a poor solvent for a drug and a bridging liquid. The selection of these solvent depends on miscibility of the solvents and solubility of drug in individual solvents. Accordingly acetone, dichloromethane, water were selected as a good solvent, bridging liquid, and poor solvent, respectively. CAR is soluble in methanol, but poorly soluble in water. Also it is soluble in dichloromethane which is immiscible in water. Hence, this solvent system was used in the present study. When drug polymer solution was poured into the poor solvent under agitation at selected temperature, the drug polymer solution became immediately semitransparent due to the presence of small sized emulsion droplets. Gradually emulsion droplets solidified along with diffusion of the good solvents, as bridging liquid dichloromethane was commixed with good solvent, when the good solvent in the droplets diffused into the poor solvent, the residual dichloromethane in the droplets bridged the Aerosil, coprecipitated drug, and polymer to form spherical crystals. The Aerosil acts as a dispering agent and mass compactor, because coacervation droplets formed from the drug-polymer droplets during the solidifying period were sticky and readily coalesced, while the introduction of Aerosil efficiently prevented coalescence and produced compact spherical crystals.

#### **3.2 Optimization of process variables for preparation of spherical crystals**

To optimize the Carvedilol spherical crystallization by methanol, water, dichloromethane solvent system following parameters considered amount and mode of addition of bridging liquid, stirring speed and temperature. (Table 2).


Table 2. Parameters affecting spherical agglomeration
