**2.2.8 Dissolution rate studies**

The dissolution rate studies of carvedilol alone and its spherical agglomerates were performed in triplicate in a dissolution apparatus (Electrolab, India) using the paddle method (USP Type II). Dissolution studies were carried out using 900 ml of 0.1N HCl (pH 1.2) at 37 ± 0.5 0C at 50 rpm as per US FDA guidelines (U.S. Food and drug administration [USFDA], 2010 and Bhutani et al., 2007.). 12.5 mg of carvedilol or its equivalent amount of

Preparation of Carvedilol Spherical Crystals Having Solid Dispersion Structure

1 Conc. of Bridging Liquid (Dichloromethane)

4 Mode of addition of bridging

Table 2. Parameters affecting spherical agglomeration

**S.No. Samples Drug Content Carr's Index Hausner** 

**3.5 FTIR, DSC and powder X-ray studies** 

aMean ± SD, n = 3; bSignificantly different compared to pure CAR (p<0.05).

liquid

**3.3 Drug content study** 

Table 3.

its spherical crystals

**3.4 Micromeritic properties** 

by the Emulsion Solvent Diffusion Method and Evaluation of Its *in vitro* Characteristics 647

1 ml No agglomeration 2 ml Agglomeration 3 ml No agglomeration

1200 rpm Irregular shape and small

Whole at a time Crystals of irregular geometry Drop wise Spherical agglomerates

30 min Spherical agglomerates

1000 rpm Spherical

**S.No. Parameter Variables Observation** 

2 Agitation speed 800 rpm Spherical but large

3 Agitation time 15 min Incomplete agglomerates

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

Pure CAR could not pass through the funnel during the angle of repose experiment which could be due to the irregular shape and high fineness of the powder, which posed hurdles in the uniform flow from the funnel. It exhibited poor flowability and packability as indicated by Hausner ratio (1.52) and Carr's Index (34.37%). All agglomerates showed excellent flowability and packability (Angle of repose: 23-280; Carr's Index: 15-18%; Hausner ratio: 1.13-1.17) when compared to pure CAR. The improved flowability of agglomerates may be due to good sphericity and larger size of agglomerates. During the tapping process, smaller agglomerates might have infiltrated into the voids between larger particles, which could result improved packability (lower CI). The results of micromeritic properties are shown in

**Ratio** 

1. CAR 100.0±0.0 34.37±1.79 1.52±1.26 --- 71.55±5.37 21.0 ± 0.51 2. CP681 94.4±2.37 17.53±1.49b 1.15±2.67b 27.12±2.43 112.7±31.26b 32.20 ± 1.32 3. CP682 92.31±2.02 15.64±1.43b 1.13±2.21b 25.36±0.67 136.43±18.57b 39.04 ± 1.65b 4. CP1271 94.19±1.15 18.63±2.90b 1.17±1.82b 28.42±0.23 88.92±25.38b 58.08 ± 1.28b 5. CP1272 92.12±1.60 17.24±1.87b 1.14±1.53b 23.05±0.89 102.03±20.11b 64.25 ± 1.31b

Table 3. Micromeritics, Drug Content, Particle size, aqueous solubility data of carvedilol and

The FTIR spectra of CAR as well as its spherical crytals are presented in Figure 3. FTIR of CAR showed a characteristic peaks at 3343.96 (N-H str. Aromatic Amines), 3062.41 (C-H str.

**Angle of Repose** 

**Particle Size (µm)** 

**Aqueous Solubility (µgmL-1)** 

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 obtained from the dissolution studies were statistically validated using ANOVA.

#### **2.2.9 Dissolution efficiency studies**

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

$$\text{Lissolution Efficiency} = \frac{\int\_{y}^{t} ydt}{y100(tz - t1)} \times 100\tag{3}$$
