**3.3 Drug content study**

646 Advances in Crystallization Processes

spherical agglomerates were added to 900 ml of 0.1N HCl (pH 1.2). Samples (5 ml) were withdrawn at time intervals of 10, 20, 30, and 60 min. The volume of dissolution medium was adjusted to 900 ml by replacing each 5 ml aliquot withdrawn with 5 ml of fresh 0.1N HCl (pH 1.2). The solution was immediately filtered, suitably diluted and the concentrations of carvedilol in samples were determined spectrophotometrically at 286 nm. The results

The dissolution efficiency (DE) of the batches was calculated by the method mentioned by Khan (Khan, 1975). It is defined as the area under the dissolution curve between time points t1 and t2 expressed as a percentage of the curve at maximum dissolution, y100, over the same time period or the area under the dissolution curve up to a certain time, t, (measured using trapezoidal rule) expressed as a percentage of the area of the rectangle described by 100% dissolution in the same time. DE60 values were calculated from dissolution data and

Dissolution Efficiency = 100

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.

liquid, stirring speed and temperature. (Table 2).

**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

0

*t ydt y tt*

2 1

(3)

100( )

obtained from the dissolution studies were statistically validated using ANOVA.

**2.2.9 Dissolution efficiency studies** 

**3. Result and discussion** 

**3.1 Preparation of spherical crystals** 

used to evaluate the dissolution rate (Anderson et al., 1998).

Percent drug content was found to be in the range of 92.12±1.60 to 94.4±2.37 (Table 3).
