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The structure determination of diclofenac embedded in a diclofenac-containing chitosan matrix using conventional X-ray powder diffraction data is demonstrated. It reveals that sodium diclofenac, the starting material in the preparation of a controlled-release diclofenac-containing chitosan matrix, changes to diclofenac acid in space group C2/c in the matrix. Simple methods were employed for handling the sample to obtain X-ray powder diffraction data of sufficiently high quality for the determination of the crystal structure of diclofenac embedded in chitosan. These involved grinding and sieving several times through a micro-mesh sieve to obtain a suitable particle size and a uniformly spherical particle shape. A traditional technique for structure solution from X-ray powder diffraction data was applied. The X-ray diffraction intensities were extracted using Le Bail's method. The structure was solved by direct methods from the extracted powder data and refined using the Rietveld method. For comparison, the single-crystal structure of the same drug was also determined. The result shows that the crystal structure solved from conventional X-ray powder diffraction data is in good agreement with that of the single crystal. The deviations of the differences in bond lengths and angles are of the order of 0.030 Å and 0.639°, respectively.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0021889804002353/ks0188sup1.cif
Contains datablocks I, II

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0021889804002353/ks0188Isup2.hkl
Structure factors for diclofenac from single crystal data

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0021889804002353/ks0188IIsup3.hkl
Structure factors for diclofenac from powder data

txt

Text file https://doi.org/10.1107/S0021889804002353/ks0188sup4.txt
Powder data for diclofenac containing chitosan matrix

txt

Text file https://doi.org/10.1107/S0021889804002353/ks0188sup5.txt
Powder data for diclofenac sodium

txt

Text file https://doi.org/10.1107/S0021889804002353/ks0188sup6.txt
Powder data for chitosan

CCDC references: 251387; 251388

Computing details top

For both compounds, program(s) used to refine structure: SHELXL97 (Sheldrick, 1997).

Figures top
[Figure 1]
[Figure 2]
[Figure 3]
[Figure 4]
[Figure 5]
[Figure 6]
[Figure 7]
(I) top
Crystal data top
C14H11Cl2NO2V = 2688.40 (8) Å3
Mr = 296.14Z = 8
?, ?F(000) = 1216
a = 20.2906 (4) ÅDx = 1.463 Mg m3
b = 6.9952 (1) ÅMo Kα radiation, λ = 0.71073 Å
c = 20.1137 (4) ŵ = 0.48 mm1
α = 90°T = 293 K
β = 109.663 (1)° × × mm
γ = 90°
Data collection top
Radiation source: fine-focus sealed tubeRint = 0.019
Graphite monochromatorθmax = 24.7°, θmin = 8.2°
6188 measured reflectionsh = 2323
2197 independent reflectionsk = 86
1911 reflections with I > 2σ(I)l = 2318
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.034Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.094H atoms treated by a mixture of independent and constrained refinement
S = 1.02 w = 1/[σ2(Fo2) + (0.0555P)2 + 1.2359P]
where P = (Fo2 + 2Fc2)/3
2197 reflections(Δ/σ)max = 0.038
216 parametersΔρmax = 0.21 e Å3
0 restraintsΔρmin = 0.28 e Å3
Crystal data top
C14H11Cl2NO2γ = 90°
Mr = 296.14V = 2688.40 (8) Å3
?, ?Z = 8
a = 20.2906 (4) ÅMo Kα radiation
b = 6.9952 (1) ŵ = 0.48 mm1
c = 20.1137 (4) ÅT = 293 K
α = 90° × × mm
β = 109.663 (1)°
Data collection top
6188 measured reflections1911 reflections with I > 2σ(I)
2197 independent reflectionsRint = 0.019
Refinement top
R[F2 > 2σ(F2)] = 0.0340 restraints
wR(F2) = 0.094H atoms treated by a mixture of independent and constrained refinement
S = 1.02Δρmax = 0.21 e Å3
2197 reflectionsΔρmin = 0.28 e Å3
216 parameters
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.22591 (8)0.3689 (2)0.33540 (9)0.0390 (4)
C20.23892 (10)0.4480 (2)0.27761 (10)0.0461 (4)
C30.18921 (11)0.4454 (3)0.21117 (10)0.0522 (5)
C40.12472 (11)0.3628 (3)0.20170 (10)0.0508 (5)
C50.11032 (10)0.2842 (3)0.25842 (9)0.0442 (4)
C60.16006 (8)0.2874 (2)0.32571 (8)0.0369 (4)
C70.09028 (8)0.0932 (2)0.38114 (8)0.0380 (4)
C80.08254 (9)0.0869 (3)0.34864 (9)0.0437 (4)
C90.02680 (11)0.2069 (3)0.34521 (11)0.0548 (5)
C100.02120 (12)0.1530 (3)0.37617 (11)0.0586 (5)
C110.01392 (10)0.0186 (3)0.41116 (10)0.0521 (5)
C120.04097 (9)0.1392 (2)0.41314 (9)0.0416 (4)
C130.28201 (10)0.3714 (3)0.40770 (11)0.0505 (5)
C140.27049 (9)0.5347 (3)0.45099 (9)0.0469 (4)
N10.14675 (8)0.2131 (2)0.38561 (8)0.0439 (4)
O10.22098 (8)0.5375 (2)0.47297 (7)0.0607 (4)
O20.31588 (8)0.6732 (2)0.46169 (9)0.0640 (4)
Cl10.04921 (3)0.35561 (7)0.45803 (3)0.0600 (2)
Cl20.14508 (3)0.16736 (7)0.31430 (3)0.0620 (2)
H10.3026 (16)0.775 (5)0.4823 (17)0.099 (10)*
H1N0.1553 (11)0.281 (3)0.4167 (11)0.050 (6)*
H20.2816 (12)0.503 (3)0.2848 (10)0.054 (5)*
H30.1970 (11)0.498 (3)0.1708 (12)0.062 (6)*
H40.0887 (12)0.364 (3)0.1572 (13)0.064 (6)*
H50.0673 (12)0.230 (3)0.2518 (11)0.056 (5)*
H90.0251 (12)0.328 (4)0.3222 (12)0.068 (6)*
H100.0606 (14)0.232 (4)0.3711 (12)0.074 (7)*
H110.0457 (12)0.054 (3)0.4328 (11)0.056 (5)*
H13A0.2803 (11)0.253 (4)0.4329 (11)0.060 (6)*
H13B0.3251 (13)0.381 (3)0.4015 (11)0.061 (6)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0373 (8)0.0317 (8)0.0505 (9)0.0001 (6)0.0183 (7)0.0081 (7)
C20.0484 (10)0.0341 (9)0.0657 (12)0.0077 (8)0.0324 (9)0.0083 (8)
C30.0719 (13)0.0389 (10)0.0552 (11)0.0066 (9)0.0338 (10)0.0002 (8)
C40.0614 (12)0.0425 (10)0.0454 (10)0.0035 (8)0.0139 (9)0.0030 (8)
C50.0405 (9)0.0415 (9)0.0487 (9)0.0063 (7)0.0127 (7)0.0003 (7)
C60.0385 (8)0.0303 (8)0.0457 (9)0.0018 (6)0.0189 (7)0.0032 (6)
C70.0400 (8)0.0380 (9)0.0367 (8)0.0010 (7)0.0138 (7)0.0043 (7)
C80.0500 (9)0.0390 (9)0.0467 (9)0.0023 (8)0.0225 (8)0.0043 (7)
C90.0697 (12)0.0396 (10)0.0581 (11)0.0115 (9)0.0255 (10)0.0006 (9)
C100.0585 (12)0.0571 (12)0.0646 (12)0.0163 (10)0.0265 (10)0.0075 (9)
C110.0480 (10)0.0624 (12)0.0536 (10)0.0003 (9)0.0272 (9)0.0118 (9)
C120.0457 (9)0.0413 (9)0.0387 (8)0.0048 (7)0.0155 (7)0.0058 (7)
C130.0366 (9)0.0493 (11)0.0627 (12)0.0029 (8)0.0129 (8)0.0078 (9)
C140.0423 (9)0.0500 (11)0.0422 (9)0.0101 (8)0.0059 (7)0.0054 (8)
N10.0456 (8)0.0468 (9)0.0415 (8)0.0110 (7)0.0177 (6)0.0065 (7)
O10.0655 (8)0.0605 (9)0.0640 (8)0.0227 (7)0.0321 (7)0.0213 (7)
O20.0580 (8)0.0611 (9)0.0770 (10)0.0227 (7)0.0280 (7)0.0236 (7)
Cl10.0714 (4)0.0545 (3)0.0610 (3)0.0040 (2)0.0314 (3)0.0103 (2)
Cl20.0725 (4)0.0480 (3)0.0793 (4)0.0092 (2)0.0437 (3)0.0030 (2)
Geometric parameters (Å, º) top
C1—C21.391 (3)C7—C81.404 (2)
C1—C61.404 (2)C8—C91.391 (3)
C1—C131.515 (3)C8—Cl21.7301 (18)
C2—C31.377 (3)C9—C101.374 (3)
C3—C41.384 (3)C10—C111.374 (3)
C4—C51.383 (3)C11—C121.387 (3)
C5—C61.390 (2)C12—Cl11.7414 (18)
C6—N11.419 (2)C13—C141.501 (3)
C7—N11.398 (2)C14—O11.226 (2)
C7—C121.397 (2)C14—O21.304 (2)
C2—C1—C6118.99 (16)C9—C8—Cl2118.49 (15)
C2—C1—C13120.32 (16)C7—C8—Cl2119.71 (13)
C6—C1—C13120.68 (16)C10—C9—C8120.03 (19)
C3—C2—C1121.52 (17)C9—C10—C11120.11 (19)
C2—C3—C4119.28 (18)C10—C11—C12119.55 (18)
C3—C4—C5120.32 (19)C11—C12—C7122.61 (17)
C4—C5—C6120.73 (17)C11—C12—Cl1118.67 (14)
C5—C6—C1119.14 (15)C7—C12—Cl1118.72 (13)
C5—C6—N1122.51 (15)C14—C13—C1110.63 (15)
C1—C6—N1118.35 (15)O1—C14—O2123.16 (18)
N1—C7—C12122.04 (15)O1—C14—C13121.87 (16)
N1—C7—C8121.94 (15)O2—C14—C13114.95 (17)
C12—C7—C8115.86 (15)C7—N1—C6123.45 (14)
C9—C8—C7121.76 (17)
(II) top
Crystal data top
C14H11Cl2NO2V = 2688.9 (17) Å3
Mr = 296.14Z = 8
?, ?F(000) = 1216
a = 20.298 (4) ÅDx = 1.463 Mg m3
b = 6.993 (4) ÅMo Kα radiation, λ = 0.71073 Å
c = 20.107 (4) ŵ = 0.48 mm1
α = 90.00 (2)°T = 293 K
β = 109.60 (2)° × × mm
γ = 90.00 (2)°
Data collection top
Radiation source: fine-focus sealed tubeRint = 0.000
Graphite monochromatorθmax = 20.7°, θmin = 3.1°
1373 measured reflectionsh = 020
1373 independent reflectionsk = 06
606 reflections with I > 2σ(I)l = 1918
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.060H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.135 w = 1/[σ2(Fo2) + (0.0388P)2]
where P = (Fo2 + 2Fc2)/3
S = 0.81(Δ/σ)max = 0.210
1373 reflectionsΔρmax = 0.27 e Å3
78 parametersΔρmin = 0.19 e Å3
6 restraintsExtinction correction: SHELXL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 172 (63)
Crystal data top
C14H11Cl2NO2γ = 90.00 (2)°
Mr = 296.14V = 2688.9 (17) Å3
?, ?Z = 8
a = 20.298 (4) ÅMo Kα radiation
b = 6.993 (4) ŵ = 0.48 mm1
c = 20.107 (4) ÅT = 293 K
α = 90.00 (2)° × × mm
β = 109.60 (2)°
Data collection top
1373 measured reflectionsRint = 0.000
1373 independent reflectionsθmax = 20.7°
606 reflections with I > 2σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.0606 restraints
wR(F2) = 0.135H atoms treated by a mixture of independent and constrained refinement
S = 0.81(Δ/σ)max = 0.210
1373 reflectionsΔρmax = 0.27 e Å3
78 parametersΔρmin = 0.19 e Å3
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.2290 (9)0.352 (2)0.3411 (9)0.060 (6)*
C20.2376 (13)0.443 (3)0.2806 (14)0.126 (9)*
H20.28000.50370.28690.151*
C30.1883 (9)0.447 (2)0.2140 (9)0.058 (5)*
H30.19750.50760.17690.070*
C40.1305 (8)0.366 (2)0.2047 (9)0.044 (5)*
H40.09690.36190.15980.053*
C50.1168 (13)0.284 (4)0.2614 (14)0.128 (9)*
H50.07410.22390.25460.154*
C60.1650 (9)0.290 (2)0.3262 (10)0.053 (5)*
C70.0957 (19)0.110 (5)0.3792 (19)0.187 (14)*
C80.0826 (11)0.087 (4)0.3448 (12)0.112 (9)*
C90.0288 (9)0.211 (3)0.3417 (9)0.065 (6)*
H90.02400.32910.31970.078*
C100.0180 (11)0.145 (3)0.3740 (11)0.099 (8)*
H100.05720.21920.36990.119*
C110.0100 (9)0.021 (3)0.4112 (9)0.064 (6)*
H110.04040.05610.43490.076*
C120.0438 (11)0.131 (3)0.4118 (10)0.081 (7)*
C130.2910 (9)0.379 (3)0.4074 (9)0.065 (6)*
C140.2821 (11)0.551 (3)0.4498 (12)0.117 (9)*
N10.1466 (10)0.221 (3)0.3833 (10)0.098 (6)*
O10.3221 (6)0.7044 (18)0.4599 (7)0.080 (4)*
O20.2292 (6)0.5318 (15)0.4682 (6)0.057 (4)*
Cl10.0478 (3)0.3467 (7)0.4583 (3)0.085 (2)*
Cl20.1440 (3)0.1576 (7)0.3082 (3)0.083 (2)*
Geometric parameters (Å, º) top
C1—C61.31 (2)C7—C81.53 (4)
C1—C21.43 (3)C8—C91.38 (2)
C1—C131.507 (18)C8—Cl21.718 (18)
C2—C31.38 (3)C9—C101.40 (2)
C3—C41.259 (18)C10—C111.36 (2)
C4—C51.39 (2)C11—C121.33 (2)
C5—C61.34 (3)C12—Cl11.760 (17)
C6—N11.40 (2)C13—C141.52 (2)
C7—N11.27 (3)C14—O21.255 (18)
C7—C121.42 (3)C14—O11.318 (18)
C6—C1—C2110.3 (19)C9—C8—Cl2118.5 (19)
C6—C1—C13135.7 (18)C7—C8—Cl2114 (2)
C2—C1—C13113.0 (18)C8—C9—C10115.2 (19)
C3—C2—C1125 (2)C11—C10—C9124 (2)
C4—C3—C2118 (2)C12—C11—C10116.4 (19)
C3—C4—C5120 (2)C11—C12—C7132 (2)
C6—C5—C4120 (2)C11—C12—Cl1113.0 (16)
C1—C6—C5125 (2)C7—C12—Cl1115 (2)
C1—C6—N1116.2 (19)C1—C13—C14112.1 (16)
C5—C6—N1118.4 (19)O2—C14—O1126 (2)
N1—C7—C12128 (3)O2—C14—C13110.8 (17)
N1—C7—C8126 (3)O1—C14—C13123.1 (18)
C12—C7—C8105 (3)C7—N1—C6126 (3)
C9—C8—C7127 (2)

Experimental details

(I)(II)
Crystal data
Chemical formulaC14H11Cl2NO2C14H11Cl2NO2
Mr296.14296.14
Crystal system, space group?, ??, ?
Temperature (K)293293
a, b, c (Å)20.2906 (4), 6.9952 (1), 20.1137 (4)20.298 (4), 6.993 (4), 20.107 (4)
α, β, γ (°)90, 109.663 (1), 9090.00 (2), 109.60 (2), 90.00 (2)
V3)2688.40 (8)2688.9 (17)
Z88
Radiation typeMo KαMo Kα
µ (mm1)0.480.48
Crystal size (mm) × × × ×
Data collection
Diffractometer??
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
6188, 2197, 1911 1373, 1373, 606
Rint0.0190.000
θmax (°)24.720.7
(sin θ/λ)max1)0.5880.497
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.034, 0.094, 1.02 0.060, 0.135, 0.81
No. of reflections21971373
No. of parameters21678
No. of restraints06
H-atom treatmentH atoms treated by a mixture of independent and constrained refinementH atoms treated by a mixture of independent and constrained refinement
(Δ/σ)max0.0380.210
Δρmax, Δρmin (e Å3)0.21, 0.280.27, 0.19

Computer programs: SHELXL97 (Sheldrick, 1997).

 

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