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

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.

Preparation of Carvedilol Spherical Crystals Having Solid Dispersion Structure

Fig. 4. DSC thermogram of (A) – Carvedilol, (B) – CP682, (C) – CP1272.

change in crystal arrangements of CAR in its spherical crystal form.

The XRD patterns of CAR shown in figure 5. The intense peaks at 2θ of 26.160, 27.480, 36.470 and 39.340 with peak intensities (counts) 310, 256, 228 and 135 respectively obtained from CAR confirmed the crystalline form of CAR. The PXRD patterns of CAR spherical crystals could be distinguished from the pure CAR. Peaks at around 8.4, 17, 220 2θ confirms the

by the Emulsion Solvent Diffusion Method and Evaluation of Its *in vitro* Characteristics 649

Aromatic Hydrocarbon), 2923.56 (C-H str. in –CH3/ –CH2), 1592.91 (C=C str. Aromatic), 1253.5, 1214.93, 1099.23 (C-O str. in Ar C=C-O-C) cm-1. There was no considerable change in the IR peaks of the spherical agglomerates when compaired with pure CAR, which revealed that no chemical interaction had occurred between drug and polymer during agglomeration process.

Figure 4 shows the DSC thermogram of pure CAR and its spherical crystals. DSC thermogram of CAR showed endothermic peak at 120.470C, which represented melting of carvedilol. There was negligible change in the melting point endotherms of prepared spherical crystals compared to pure drug (CP682 = 115.470C, CP1272 = 118.670C). The endotherms at 57.050C and 59.070C ascribed to the melting of Poloxamer F68 and Poloxamer F127 respectively. This observation further supports the IR spectroscopy results, which indicated the absence of any interactions between the drug and additives used in the preparation. However, there was a decrease, although very small, in the melting point of the drug in the spherical crystals compared to that of pure carvedilol. This indicates the little amorphization of carvedilol when prepared in the form of spherical crystals.

Fig. 3. FTIR spectra of (A) – Carvedilol, (B) – CP682, (C) – CP1272

process.

Aromatic Hydrocarbon), 2923.56 (C-H str. in –CH3/ –CH2), 1592.91 (C=C str. Aromatic), 1253.5, 1214.93, 1099.23 (C-O str. in Ar C=C-O-C) cm-1. There was no considerable change in the IR peaks of the spherical agglomerates when compaired with pure CAR, which revealed that no chemical interaction had occurred between drug and polymer during agglomeration

Figure 4 shows the DSC thermogram of pure CAR and its spherical crystals. DSC thermogram of CAR showed endothermic peak at 120.470C, which represented melting of carvedilol. There was negligible change in the melting point endotherms of prepared spherical crystals compared to pure drug (CP682 = 115.470C, CP1272 = 118.670C). The endotherms at 57.050C and 59.070C ascribed to the melting of Poloxamer F68 and Poloxamer F127 respectively. This observation further supports the IR spectroscopy results, which indicated the absence of any interactions between the drug and additives used in the preparation. However, there was a decrease, although very small, in the melting point of the drug in the spherical crystals compared to that of pure carvedilol. This indicates the little

amorphization of carvedilol when prepared in the form of spherical crystals.

Fig. 4. DSC thermogram of (A) – Carvedilol, (B) – CP682, (C) – CP1272.

The XRD patterns of CAR shown in figure 5. The intense peaks at 2θ of 26.160, 27.480, 36.470 and 39.340 with peak intensities (counts) 310, 256, 228 and 135 respectively obtained from CAR confirmed the crystalline form of CAR. The PXRD patterns of CAR spherical crystals could be distinguished from the pure CAR. Peaks at around 8.4, 17, 220 2θ confirms the change in crystal arrangements of CAR in its spherical crystal form.

Preparation of Carvedilol Spherical Crystals Having Solid Dispersion Structure

spherical in shape which enabled them to flow very easily.

**3.6 Scanning electron microscopy** 

by the Emulsion Solvent Diffusion Method and Evaluation of Its *in vitro* Characteristics 651

The results of surface morphology studies are shown in Figure 6. The SEM results revealed the spherical structure of agglomerates. The surface morphology studies also revealed that the agglomerates were formed by very small crystals, which were closely compacted into spherical form. These photo-micrographs show that the prepared agglomerates were

A

B

Fig. 5. XRD patterns of (A) – Carvedilol, (B) – CP682, (C) – CP1272.

#### **3.6 Scanning electron microscopy**

650 Advances in Crystallization Processes

Fig. 5. XRD patterns of (A) – Carvedilol, (B) – CP682, (C) – CP1272.

The results of surface morphology studies are shown in Figure 6. The SEM results revealed the spherical structure of agglomerates. The surface morphology studies also revealed that the agglomerates were formed by very small crystals, which were closely compacted into spherical form. These photo-micrographs show that the prepared agglomerates were spherical in shape which enabled them to flow very easily.

A

B

Preparation of Carvedilol Spherical Crystals Having Solid Dispersion Structure

by the Emulsion Solvent Diffusion Method and Evaluation of Its *in vitro* Characteristics 653

0 10 20 30 40 50 60

behind the greater solubility and dissolution of CAR from its agglomerated form may resemble the solid dispersion mechanism despite the larger particle size of agglomerates. This effect may be due to improved wettability of the surface of agglomerates by the adsorption of poloxamer onto the surfaces of crystals. These results confirm that the dissolution rate of carvedilol was increased in form of spherical crystals when compared to

CAR-poloxamer spherical crystals were prepared successfully by ESD method. The resultant crystals have the desired micromeritic properties, such as flowability and packability. In the present investigation Poloxamer F68 and Poloxamer F127 has significantly improved dissolution rate of carvedilol. However *in vivo* bioavailability studies are required to ensure whether, the results obtain in this investigation can be extrapolated to

The authors gratefully acknowledge Dr. Reddy's Laboratory, Hyderabad, India for the gift sample of Carvedilol. The authors are thankful to AISSMS college of Pharmacy, Pune, India for providing FTIR and DSC facilities. Also the authors would like to thank Shivaji

Fig. 7. Dissolution profile of CAR and its agglomerates. (Mean ±SD, n = 3.)

Time (Min)

0

20

40

60

CAR (% Drug Release)

its pure form.

**4. Conclusion** 

the *in vivo* conditions.

**5. Acknowledgments** 

University, Kolhapur, India for providing PXRD facility.

80

100

Fig. 6. SEM of (A) – Carvedilol, (B) – CP682, (C) – CP1272
