Metaxalone polymorphs
The invention provides two crystalline forms A and B of the skeletal muscle relaxant and anxiolytic agent, Metaxalone of formula (I), and a process for preparation thereof. The two crystalline forms A and B are bioavailable. The invention further provides pharmaceutical compositions comprising the two bioavailable crystalline forms, useful for the relief of discomforts associated with acute, painful musculoskeletal conditions.
1. A crystalline Metaxalone Form B exhibiting an X-ray (powder) diffraction pattern characterized by 2θ±2 angles and d values as represented in the following table:
Angle (° 2θ)
d-value (° A)
10.261
8.61422
11.244
7.86292
14.189
6.23687
15.696
5.64131
16.275
5.44197
16.643
5.32239
17.294
5.12360
18.550
4.77930
19.009
4.66497
19.499
4.54890
20.723
4.28280
21.593
4.11209
22.404
3.96508
23.768
3.74063
24.529
3.62615
25.238
3.52594
25.759
3.45585
26.442
3.36811
27.076
3.29066
27.699
3.21796
28.176
3.16469
29.668
3.00878
29.989
2.97733
30.850
2.89609
31.613
2.82793
32.693
2.77245
34.240
2.61675
35.432
2.53142
37.028
2.42586
37.511
2.39574.
2. The crystalline Metaxalone Form B according to claim 1 , exhibiting an I.R spectrum with V max at about 1722 cm −1 and 1753 cm −1 for the carbonyl group.
3. The crystalline Metaxalone Form B according to claim 1 , exhibiting an endotherm at about 121.5° C. and 122.48° C. in its Differential Scanning Calorimeter (DSC) thermogram.
4. The crystalline Metaxalone Form B according to claim 1 , having a C max value of 40.73±2.8 μg/ml.
5. The crystalline Metaxalone Form B according to claim 1 , having a T max value of 2.08±1.4 hr.
6. The crystalline Metaxalone Form B according to claim 1 , having a half-life value of 4.49±1.7 hr.
7. The crystalline Metaxalone Form B according to claim 1 , having an AUC last value of 333.32±159.9 hrμg/ml; AUC inf value of 389.07±200.6 hrμg/ml; a MRT last value of 5.50±1.8 hr. and a Cl obs value of 472.72±214.7 ml/hr/kg.