Sie sind auf Seite 1von 6

RESEARCH ARTICLE – Pharmaceutics, Drug Delivery and Pharmaceutical Technology

The Rietveld Method as a Tool to Quantify the Amorphous Amount


of Microcrystalline Cellulose
LAYSA PIRES DE FIGUEIREDO, FABIO FURLAN FERREIRA

Centro de Ciências Naturais e Humanas (CCNH), Universidade Federal do ABC (UFABC), Santo André, SP CEP: 09210-580, Brazil

Received 17 December 2013; revised 14 January 2014; accepted 31 January 2014


Published online 1 March 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/jps.23909

ABSTRACT: With the use of X-ray powder diffraction data and the Rietveld method, we verified that both microcrystalline cellulose PH-
101 and PH-102 presented differences in the crystallinity degree. The results revealed these samples are semicrystalline in nature and via
Rietveld refinements, it was possible, adding a known amount of an internal standard of corundum to the samples, to perform quantitative
phase analyses, which allowed us to determine the amorphous amount of the studied samples: 63.7(11) wt % in microcrystalline cellulose
PH-101 and 51.0(11) wt % in microcrystalline cellulose PH-102. An important contribution of this work refers to the attempt of using
this simple method, permitting to evaluate the degree of crystallinity of microcrystalline cellulose. 
C 2014 Wiley Periodicals, Inc. and the

American Pharmacists Association J Pharm Sci 103:1394–1399, 2014


Keywords: microcrystalline cellulose PH-101; microcrystalline cellulose PH-102; crystallinity; X-ray powder diffraction; Rietveld
method; FTIR; dehydration; solid state

INTRODUCTION Herein, we report on the investigation of the structural


characterization and quantitative phase analysis of microcrys-
Many organic compounds are able to adopt one or more pure
talline cellulose, a purified and partially depolymerized cellu-
crystalline forms of well-defined and easily identifiable config-
lose prepared by high-quality treatment with mineral acid to
uration, or an amorphous form without long-range order, de-
hydrolyze cellulose wood pulp, in order to decrease the degree of
pending on the conditions (temperature, solvent, time) under
polymerization. Figure 1 shows the molecular structure of cel-
which crystallization is induced. It is in this context the term
lulose as a carbohydrate polymer generated from repeating $-
polymorphism arises, being defined as the ability of a compound
D-glucopyranose molecules that are covalently linked through
to crystallize in two or more crystal structures with the same
acetal functions between the equatorial OH group of C(4) and
chemical composition, due to the differences in spatial arrange-
the C(1) carbon atoms ($-1,4-glucan), which is, in principle, the
ments and/or conformation of the molecules.1–4 It is notewor-
manner in which cellulose is biogenetically formed.9 As a re-
thy that polymorphism may cause a direct impact on several
sult, cellulose is an extensive, linear-chain polymer with a large
characteristics of pharmaceuticals, thus displaying unexpected
number of hydroxyl groups [three per anhydroglucose (AGU)
results, which may compromise the efficacy of the medicinal
unit] present in the thermodynamically preferred 4 C1 confor-
product.
mation. To accommodate the preferred bond angles of the acetal
As many pharmaceuticals, excipients can also present poly-
oxygen bridges, every second AGU ring is rotated 180◦ in the
morphic transformations, being a worrying factor for the phar-
plane. In this manner, two adjacent structural units define the
maceutical industries.5,6 On this basis, the choice of excipients
disaccharide cellobiose.10,11
suitable for particular formulation is a key point to the thera-
As shown in the molecular structure represented in Figure 1,
peutic efficacy of the final product. This choice must be based on
the hydroxyl groups of $-1,4-glucan cellulose are placed at
the characteristics of the substances contained in the formula-
positions C(2) and C(3) (secondary, equatorial) as well as C(6)
tion, as well as the possibility of interaction with the excipient.
(primary). The CH2 OH side group is arranged in a trans-gauche
In this context, it is essential that during the re-
(tg) position relative to the O(5)–C(5) and C(4)–C(5) bonds.9 As
search/development of formulations, one can be able to select
a result, microcrystalline cellulose has a semicrystalline struc-
the correct polymorphic form of an active pharmaceutical in-
ture, that is, part of its structure is amorphous and other is crys-
gredient as well as excipients that do not suffer any kind of
talline (Fig. 2). The crystalline regions are grouped into nuclei
interaction, ensuring that both bioavailability and the phar-
called crystallites. These crystallites, in turn, are surrounded
macological effect take place. Thus, the research of polymor-
by amorphous regions.12 The proportion between amorphous
phism in pharmaceuticals and excipients is one of the most
and crystalline regions determines the degree of crystallinity,
important subjects to be considered prior to the production of
object of study in this work.
medicaments, mainly because the lack of knowledge of differ-
ent crystalline forms can influence the production procedure
and may bring health problems to patients and financial losses Celluloses I␣ and I␤
to their manufacturers.7,8
Currently, it is known that cellulose exists in more than one
polymorphic form,14 that is, there is not a single unit cell di-
Correspondence to: Fabio Furlan Ferreira (Telephone: +55-11-4996-8370;
Fax: +55-11-4996-0090; E-mail: fabio.furlan@ufabc.edu.br) mension, showing six polymorphic forms for cellulose I, which
Journal of Pharmaceutical Sciences, Vol. 103, 1394–1399 (2014) also display polymorphism, and receive the following names:

C 2014 Wiley Periodicals, Inc. and the American Pharmacists Association cellulose I, cellulose II, cellulose IIII , cellulose IIIII , cellulose

1394 De Figueiredo and Ferreira, JOURNAL OF PHARMACEUTICAL SCIENCES 103:1394–1399, 2014


RESEARCH ARTICLE – Pharmaceutics, Drug Delivery and Pharmaceutical Technology 1395

Figure 1. Molecular structure of cellulose (n = DP, degree of polymerization).

by a pharmaceutical company that will not have its information


disclosed. The techniques used for the studies were FTIR and
XRPD together with the Rietveld method.

Fourier Transform Infrared Spectroscopy


Spectral data were recorded in the range from 4000 to 650 cm−1
Figure 2. Illustration containing crystalline regions interspersed by with a resolution of 4 cm−1 , in a Fourier transform spectrometer,
amorphous ones of cellulose. (Adapted from Ref. 13.) model 660-IR, from Varian (Palo Alto, CA, USA), equipped with
an attenuated total reflection accessory and a ZnSe crystal.
FTIR measurements were conducted at the Multiuser Experi-
IVI , and cellulose IVII , although the existence of cellulose IVI is
mental Centre/Universidade Federal do ABC (CEM/UFABC).
controversial.15
Among those, cellulose I is receiving increased attention be-
XRPD and Rietveld Refinements
cause of its potential use in bioenergy production, and accord-
ing to the literature the existence of more than one polymorphic X-ray powder diffraction data were collected on a STADI-P
form of cellulose in native samples has been shown.16,17 Today, diffractometer, from Stoe (Darmstadt, Germany), operating in
we know that cellulose I actually consisted of two polymorphic the transmission mode, using CuK"1 radiation (8 = 1.54056 Å),
forms, called I" (one-chain triclinic structure) and I$ (two-chain an accelerating voltage of 40 kV and current of 40 mA, equipped
monoclinic structure). In this scheme, native celluloses were all with a primary beam monochromator [Ge (111) curved crys-
classified into I" -rich algal-bacterial type or I$ -dominant cotton- tal], a 0.5-mm divergence slit, and a 0.3-mm circular scattering
ramie type.18 slit. The X-ray photons were detected with a linear detector
The crystal structure and hydrogen-bonding system in cel- (Mythen 1K, from Dectris(Baden, Switzerland)). The samples
lulose I$ was elucidated by the combined use of synchrotron were loaded between two 0.014-mm thick cellulose-acetate foils,
X-ray and neutron fiber diffraction.19 Oriented fibrous samples with density of 1.3 g cm−3 , and were spun during data collec-
were prepared by aligning cellulose microcrystals from tunicin, tion. Measurements were performed in the angular range from
reconstituted into oriented films. These samples diffracted 5◦ to 50◦ (2θ ), with step sizes of 0.015◦ and an integration time
both synchrotron X-rays and neutrons to better than 1 Å res- of 60 s at each 1.05◦ . These analyses were conducted in the Lab-
olution, yielding more than 300 unique reflections and an oratory of Crystallography and Structural Characterization of
unambiguous assignment of the monoclinic unit cell dimen- Materials (LCCEM) of UFABC.
sions: a = 7.784(8) Å; b = 8.201(8) Å; c = 10.380(10) Å; and For the identification of the crystal structures, both the
( = 96.55(5)◦ , in the space group P21 . Cambridge Structural Database (CSD) and Inorganic Crystal
R

The crystal and molecular structures of the cellulose I" have Structure Database (ICSD) were used; the structural char-
R

been established using synchrotron and neutron diffraction acterization of samples and the evaluation of the amorphous
data recorded from oriented fibrous samples prepared by align- amount were carried out by means of the Rietveld method21,22
ing cellulose microcrystals from the cell wall of fresh water alga using XRPD data and the Topas-Academic v. 523 software pro-
Glaucocystis nostochinearum.20 Cellulose I" crystallizes in a tri- gram. First, we refined the unit cell parameters and the zero
clinic unit cell: a = 10.400(10) Å; b = 6.717(6) Å; c = 5.962(7) Å; point of the diffractometer. The background was fitted using
" = 80.37(5)◦ ; $ = 118.08(5)◦ ; and ( = 114.80(5)◦ , having space a 12-term Chebyshev polynomial. The peak asymmetry was
group P1. adjusted using the simple axial divergence model of Cheary
It should be mentioned that the determination of the crys- and Coelho.24,25 The peak profiles were modeled using the
tal structure of cellulose by X-ray diffraction played an impor- fundamental-parameter approach25 and the preferred orienta-
tant role in the polymer science and the concept of long-chain tion of the crystals were corrected with a fourth-order spherical
molecules. In order to verify such statements and information, harmonics function. The isotropic atomic displacements (Biso )
which may serve as a subsidy for the pharmaceutical industries, of all nonhydrogen atoms were fixed to 2.8. For the hydrogen
quantitative phase analyses by means of X-ray powder diffrac- atoms, the Biso values were assumed to be 1.2 times larger than
tion (XRPD) data and the Rietveld method were used to eval- the values of the nonhydrogen atoms.
uate the amorphous amount of both microcrystalline cellulose
PH-101 and microcrystalline cellulose PH-102. Also, FTIR was
used to follow their possible differences in absorption bands. RESULTS AND DISCUSSION
Fourier Transform Infrared Spectroscopy
MATERIALS AND METHODS
The FTIR spectra for microcrystalline cellulose PH-101 and
Powdered samples of microcrystalline cellulose PH-101 and microcrystalline cellulose PH-102 samples are shown in
PH-102 (Avicel from FMC BioPolymers) were kindly provided
R
Figure 3.

DOI 10.1002/jps.23909 De Figueiredo and Ferreira, JOURNAL OF PHARMACEUTICAL SCIENCES 103:1394–1399, 2014
1396 RESEARCH ARTICLE – Pharmaceutics, Drug Delivery and Pharmaceutical Technology

Figure 4. X-ray diffractograms of microcrystalline cellulose PH-101


Figure 3. FTIR spectra for microcrystalline cellulose PH-101 and and microcrystalline cellulose PH-102 collected in transmission mode.
microcrystalline cellulose PH-102 samples, obtained with a resolution The X-ray diffractogram of microcrystalline cellulose PH-102 were off-
of 4 cm−1 in the region from 4000 to 650 cm−1 . set for better visualization.

Also, we can infer that both FTIR spectra are characteristic


Table 1. Location of the Main Absorption Bands of Cellulose I of cellulose I (native), as the absorption bands are similar to
(Native),26,27 Microcrystalline Cellulose PH-101 and Microcrystalline reported values in the literature27 for this polymorphic form of
Cellulose PH-102 with Their Respective Chemical Bonds cellulose.

Cellulose I 101 102 X-Ray Powder Diffraction


L (cm−1 ) Assignment
The X-ray diffractograms for both samples of microcrys-
3352 3336 3339 (OH (hydrogen bonded) talline cellulose, collected in transmission mode, are shown in
2901 2900 2900 (CH Figure 4.
1431 1430 1430 *CH2 (sym) at C-6 It can be seen that both diffractograms are character-
1373 1372 1372 *CH istic of semicrystalline materials due to the presence of a
1319 1318 1314 *CH2 (wagging) at C-6 hump, ascribed to the amorphous contribution, and some broad
1282 1289 1287 *CH peaks, related to the crystalline part.12,29–31 Also, these pat-
1236 1230 1232 *COH in plane at C-6
terns are very similar to the one displayed by cellulose I (na-
1202 1206 1204 *COH in plane at C-6
1165 1156 1161 *COC at $-glucosidic linkage
tive) with diffraction peaks at 14.7◦ , 16.3◦ , 20.8◦ , 22.5◦ , and
1032 1031 1031 (CO at C-6 34.6◦ (2θ ),31–34 but four crystalline peaks (14.7◦ , 16.3◦ , 22.5◦ , and
983 984 984 (CO at C-6 34.6◦ ) have been assumed in other studies.35 However, to really
897 897 896 (COC at $-glucosidic linkage, (COC, confirm these samples belong to this polymorphic form of cel-
(CCO, and (CCH at C-5 and C-6 lulose as well as to quantify the amorphous amount, Rietveld
refinements using the available crystallographic information
(, stretching; *, bending.
[monoclinic (I$ )] and the information provided by the manufac-
turer were performed.
Quantitative Phases Analysis with the Addition of an Internal
Table 1 displays the main absorption bands of cellulose I
Standard—Determination of Amorphous Amount
(native), microcrystalline cellulose PH-101 (named 101), and
microcrystalline cellulose PH-102 (named 102) investigated One of the most common and accurate ways to determine the
in this study, with the assignment of the respective chemical crystallinity in semicrystalline polymers is the use of X-ray
bonds.26,27 Not all absorption bands were identified, considering diffraction data. The study of crystallinity of cellulose, and con-
that FTIR spectroscopic investigations were carried out with sequently microcrystalline cellulose in the solid state, has been
the aim of evidencing that an alteration of the crystalline or- the subject of great interest of the scientific community.36 There
ganization leads to a significant simplification of the spectral is a common sense that the main variable in native cellulose
shape by a reduction in intensity or even disappearance of the crystallinity is crystallite size. However, a recent study,37 shows
characteristic bands of the crystalline domains. how the simple Segal crystallinity index can be used to evaluate
It is worth mentioning that the band at 1430 cm−1 is known crystallinity. As this method does not take into account the cor-
as the band of crystallinity, that is, a decrease in its intensity rection of many parameters, we decided not to make use of this
reflects in the reduction of the degree of crystallinity of the procedure in our work even it has been largely employed. Keep-
sample.26–28 As shown in the FTIR spectra in Figure 3, this band ing this in mind, XRPD data with the addition of an internal
is more intense for microcrystalline cellulose PH-102, which standard of corundum (SRM 676a), commercially distributed
gives us indication of the greater crystallinity for this sample. by the National Institute of Standards and Technology,38 were

De Figueiredo and Ferreira, JOURNAL OF PHARMACEUTICAL SCIENCES 103:1394–1399, 2014 DOI 10.1002/jps.23909
RESEARCH ARTICLE – Pharmaceutics, Drug Delivery and Pharmaceutical Technology 1397

Table 2. Crystallographic Data JINROO01 (CSD) and 88027 (ICSD)


that were Used as the Input Files for the Rietveld Refinement

Unit Cell JINROO01 (CSD) 88027 (ICSD)


Parameters 101 and 102 Al2 O3

a (Å) 7.784(8) 4.75919(1)


b (Å) 8.201(8) 4.75919(1)
c (Å) 10.38(1) 12.99183(1)
" (◦ ) 90 90.0
$ (◦ ) 90 90.0
( (◦ ) 96.55(5) 120.0
V (Å)3 662.6 254.84
Crystal structure Monoclinic Hexagonal
Space group P21 R3̄c

Table 3. Results of the Rietveld Refinements of Microcrystalline


Cellulose PH-101 (Named 101) and Microcrystalline Cellulose PH-102
(Named 102)
Figure 5. X-ray diffractograms of microcrystalline cellulose PH-101
and microcrystalline cellulose PH-102 with the addition of an internal Unit Cell Parametersa 101 102
standard (corundum), and the comparison with crystallographic data
88027 (corundum) retrieved from the ICSD. a (Å) 7.910(2) 7.909(1)
b (Å) 8.245(7) 8.236(6)
c (Å) 10.361(1) 10.360(1)
" (◦ ) 90 90
used in conjunction with the Rietveld method in the quantifi-
$ (◦ ) 90 90
cation procedure of the amorphous amount of both microcrys- ( (◦ ) 95.83(12) 96.36(7)
talline cellulose PH-101 and microcrystalline cellulose PH-102. V (Å3 ) 672.3(7) 670.8(5)
Figure 5 presents the X-ray diffractograms of microcrys- Crystal structure Monoclinic Monoclinic
talline cellulose PH-101 and microcrystalline cellulose PH-102 Space group P21 P21
with the addition of an internal standard of corundum used in
a
this study as well as the calculated diffraction pattern of corun- The weighted Durbin–Watson statistics (d-DW) is quite low,41 indicating that
the SDs are underestimated. There is no adequate physical model to correct the
dum (crystallographic data 88027)39 obtained from the ICSD. SD values in the Rietveld method, to make them representative of the repetition
According to the visual inspection of the X-ray diffrac- of the experiment.
tograms, it should be noted that corundum was chosen as the in-
ternal standard because it does not present overlapping peaks
with the most intense ones of the samples under study. In ad- clinic crystal system (space group P21 ) thus being attributed as
dition, the transmission geometry in which the samples were cellulose I$ , as shown in Table 3.
measured allowed us to prevent effects of preferred orienta- To perform quantitative phase analyses of both samples of
tion of the crystallites, which may affect the quantitative phase microcrystalline cellulose, a known amount of corundum was
analyses. added to the powders. Keeping in mind that also corundum
As described in the literature, two polymorphic forms of na- presents a certified amount of amorphous material, which is
tive cellulose are known;19,20 thus, the Rietveld refinements equal to 1.11 wt %,38 this information was took into account
were carried out without refining the structural coordinates, and included in the refinement file into Topas-Academic v. 5.
and they were compared with the results obtained with and As the internal standard is introduced into a known quantity,
without corrections for preferred orientation of the crystallites the calculations are performed to provide the same amount at
(four-term spherical harmonics function), using the two crystal- the end of each cycle of refinement. In other words, after each
lographic information files available. The results of the Rietveld cycle, the ratio is determined and multiplied by a scaling factor
refinements were consistent with the information found in the to provide the same amount added. All other phases are cor-
literature that cellulose derived from wood pulp crystallizes rected by the same scale factor. The sum of all phases refined,
under a monoclinic (cellulose I$ ) crystal system. including the internal standard, should be less than 100%. The
Considering only a simple visual analysis of the Rietveld difference to 100% is the proportion of the amorphous materi-
plots, one cannot distinguish between the fits what is better. als. After deconvoluting the known amount of corundum added
Some statistical criteria were used to evaluate the quality of the to the samples (11.00 wt % for microcrystalline PH-101 and
refinements. Among them, the most important ones are RBragg , 12.56 wt % microcrystalline PH-102), the amorphous quan-
Rwp , Rexp , and P 2 .40 Taking into account that the values obtained tification resulted in 63.7(11) wt % for microcrystalline cellu-
for these parameters are considered good for the adjustments lose PH-101 and 51.0(11) wt % for microcrystalline cellulose
performed,40 we can see that the choice of the monoclinic crystal PH-102.
structure better describes the studied samples. The Rietveld graphs displayed in Figures 6 and 7 presented
In Table 2 are shown the crystallographic data of cards a good fit between the observed and calculated data. The statis-
JINROO0119 (CSD) and 8802739 (ICSD) used as input files to tical parameters40 also indicated the quality of the refinements.
perform the Rietveld refinements. The knowledge of such information is important to the selec-
It was verified that microcrystalline cellulose PH-101 and tion of candidate compounds for the formulation of new medica-
microcrystalline cellulose PH-102 crystallized under a mono- ments because the degree of crystallinity can influence various

DOI 10.1002/jps.23909 De Figueiredo and Ferreira, JOURNAL OF PHARMACEUTICAL SCIENCES 103:1394–1399, 2014
1398 RESEARCH ARTICLE – Pharmaceutics, Drug Delivery and Pharmaceutical Technology

Rietveld method, it was possible to identify the samples as


cellulose I (native), which, in turn, has two polymorphic forms
known as cellulose I" and I$ . However, after a careful analysis of
the statistical indices from these refinements, one can see that
microcrystalline cellulose PH-101 as well as microcrystalline
cellulose PH-102 crystallized in a monoclinic crystal system
(space group P21 ), being classified as cellulose I" . Quantitative
phase analysis with the addition of an internal standard for
determination of the amorphous amount is considered new in
relation to what has been performed to date and constitutes an
important tool to evaluate the degree of crystallinity, not just
of microcrystalline cellulose, but of all samples that have some
crystalline order.
The FTIR results showed that it is possible to classify the
samples as the polymorphic form I (native); however, only with
this technique, it has not been possible to distinguish them
θ ° between cellulose I" or cellulose I$ .
Figure 6. Rietveld graph of microcrystalline cellulose PH-101 with
the addition of the internal standard (corundum). Goodness-of-fit in-
dicator as well as R-factors40 were: P 2 = 1.08, Rwp = 2.89%, Rexp = Acknowledgments
2.67%, and RBragg = 1.00. The authors thank the financial support from São Paulo Re-
search Foundation (FAPESP—proc. nr. 2008/10537-3), Na-
tional Council for Scientific and Technological Development
(CNPq—proc. nrs. 305186/2012-4 and 477296/2011-4), and
UFABC for a scholarship (L.P.F.).

REFERENCES
1. Ansel HC, Popovich NG, Allen LV. 2000. Farmacotécnica: Formas
farmacêuticas e sistemas de liberação de fármacos. 6th ed., São Paulo:
Premier: Cia. dos Livros, p. 568.
2. Vippagunta SR, Brittain HG, Grant DJW. 2001. Crystalline solids.
Adv Drug Deliv Rev 48(1):3–26.
3. Rodriguez-Spong B, Price CP, Jayasankar A, Matzger AJ, Rodriguez-
Hornedo N. 2004. General principles of pharmaceutical solid polymor-
phism: A supramolecular perspective. Adv Drug Deliv Rev 56(3):241–
274.
4. Ritschel WA, Kearns GL. 2009. Handbook of basic pharmacokinet-
θ ° ics: Including clinical applications. 7th ed., Washington, DC: American
Pharmacists Association, p. 490.
Figure 7. Rietveld graph of microcrystalline cellulose PH-102 with 5. Bernstein J. 2007. Polymorphism in molecular crystals. 1 ed. Oxford:
the addition of the internal standard (corundum). Goodness-of-fit in- Clarendon Press, p. 424.
dicator as well as R-factors40 were: P 2 = 0.96, Rwp = 2.52%, Rexp = 6. de Figueiredo LP. 2012. Análise de excipientes em comprimidos de
2.62%, and RBragg = 0.51. fármacos comercializados. Santo André, SP: Universidade Federal do
ABC (UFABC), p. 171.
7. Estévez-Carrizo FE. 2000. Estudio de bioequivalencia: Enfoque
properties of pharmaceuticals and excipients, thus affecting metodológico y aplicaciones prácticas en la evaluación de medicamentos
their stability. The results obtained in the present work refer genéricos; Bioequivalence studies: Methodological approach and practi-
cal applications for the assessment of generic drugs. Rev Med Uruguay
only to the specific samples studied. Some deviations from the
16(2):133–143.
values obtained may occur because of the conditions in which
8. Marzo A. 1997. Clinical pharmacokinetic registration file for NDA
the experiments are carried out (controlled humidity condi- and ANDA procedures. Pharm Res 36(6):425–450.
tions, for example). 9. Howard RL, Abotsi E, Jansen van Rensburg EL, Howard S. 2003.
Lignocellulose biotechnology: Issues of bioconversion and enzyme pro-
duction. African J Biotech 2(12):602–619.
CONCLUSIONS 10. Haward SJ, Sharma V, Butts CP, McKinley GH, Rahatekar SS.
2012. Shear and extensional rheology of cellulose/ionic liquid solutions.
Through the X-ray diffractograms, it was possible to quan-
Biomacromolecules 13(5):1688–1699.
tify the amorphous amount of microcrystalline cellulose PH-
11. Klemm D, Heublein B, Fink HP, Bohn A. 2005. Cellulose: Fasci-
101 and microcrystalline cellulose PH-102 via Rietveld refine- nating biopolymer and sustainable raw material. Angew Chem Int Ed
ments with the addition of an internal standard (Al2 O3 ), and 44:3358–3393.
we found that the microcrystalline cellulose PH-101 has lower 12. Ek R, Alderborn G, Nyström C. 1994. Particle analysis of micro-
crystallinity [63.7(11) wt %] when compared with microcrys- crystalline cellulose: Differentiation between individual particles and
talline cellulose PH-102 [51.0(11) wt %]. In addition, with the their agglomerates. Int J Pharm 111(1):43–50.

De Figueiredo and Ferreira, JOURNAL OF PHARMACEUTICAL SCIENCES 103:1394–1399, 2014 DOI 10.1002/jps.23909
RESEARCH ARTICLE – Pharmaceutics, Drug Delivery and Pharmaceutical Technology 1399

13. Quiroz-Castañeda RE, Folch-Mallol JL. 2013. Hydrolysis of 28. Tomaz RMAG, Bittencourt E, Sabino NP, Kondo JI. 1994.
biomass mediated by cellulases for the production of sugars. In Determinação dos ı́ndices de cristalinidade de fibras celulósicas. Bra-
Sustainable degradation of lignocellulosic biomass—Techniques, ap- gantia 53:121–126.
plications and commercialization; Chandel AK, da Silva SS, Eds., 29. Park S, Baker JO, Himmel ME, Parilla PA, Johnson DK. 2010.
p. 275. Cellulose crystallinity index: Measurement techniques and their im-
14. O’Sullivan AC. 1997. Cellulose: The structure slowly unravels. Cel- pact on interpreting cellulase performance. Biotechnol. Biofuels 3:1–
lulose 4(3):173–207. 10.
15. Wada M, Heux L, Sugiyama J. 2004. Polymorphism of cellulose I 30. Wang Z, McDonald AG, Westerhof RJ, Kersten SR, Cuba-Torres
family: Reinvestigation of cellulose IV(I). Biomacromolecules 5:1385– CM, Ha S, Pecha B, Garcia-Perez M. 2013. Effect of cellulose crys-
1391. tallinity on the formation of a liquid intermediate and on product dis-
16. Atalla RH, Vanderhart DL. 1984. Native cellulose: A composite of tribution during pyrolysis. J Anal Appl Pyrol 100:56–66.
two distinct crystalline forms. Science 223(4633):283–285. 31. Garvey CJ, Parker IH, Simon GP. 2005. On the interpretation of
17. Sugiyama J, Persson J, Chanzy H. 1991. Combined infrared and X-ray diffraction powder patterns in terms of the nanostructure of cel-
electron diffraction study of the polymorphism of native celluloses. lulose I fibres. Macromol Chem Phys 206(15):1568–1575.
Macromolecules 24:2461–2466. 32. Suesat J, Suwan Ruji PJ. 2011. Preparation and properties of micro-
18. Wada M, Okano T, Sugiyama J. 1997. Synchrotron-radiated X-ray crystalline cellulose from corn residues. Adv Mater Res 332–334:1781–
and neutron diffraction study of native cellulose. Cellulose 4:221–232. 1784.
19. Nishiyama Y, Langan P, Chanzy H. 2002. Crystal structure and 33. Nelson ML, O’Connor RT, 1964. Relation of certain infrared bands
hydrogen-bonding system in cellulose I$ from synchrotron X-ray and to cellulose crystallinity and crystal lattice type. Part II. A new infrared
neutron fiber diffraction. J Am Chem Soc 124(31):9074–9082. ratio for estimation of crystallinity in celluloses I and II. J Appl Pol
20. Nishiyama Y, Sugiyama J, Chanzy H, Langan P. 2003. Crystal Sci 107:1325–1341.
structure and hydrogen bonding system in cellulose i" from synchrotron 34. Hult E-L, Iversen T, Sugiyama J. 2003. Characterization of the
X-ray and neutron fiber diffraction. J Am Chem Soc 125(47):14300– supermolecular structure of cellulose in wood pulp fibres. Cellu-
14306. lose 10:103–110.
21. Rietveld HM. 1967. Line profiles of neutron powder-diffraction 35. He J, Cui S, Wang S-y. 2008. Preparation and crystalline analysis of
peaks for structure refinement. Acta Crystallogr 22(1):151–152. high-grade bamboo dissolving pulp for cellulose acetate. J Appl Polym
22. Rietveld HM. 1969. A profile refinement method for nuclear and Sci 107(2):1029–1038.
magnetic structures. J Appl Crystallogr 2(2):65–71. 36. Thygesen A, Oddershede J, Lilholt H, Thomsen AB, Ståhl K. 2005.
23. Coelho AA, Evans J, Evans I, Kern A, Parsons S. 2011. The TOPAS On the determination of crystallinity and cellulose content in plant
symbolic computation system. Powder Diffr 26:s22–s25. fibres. Cellulose 12(6):563–576.
24. Cheary RW, Coelho AA. 1998. Axial divergence in a conventional 37. French AD, Cintrón MS. 2013. Cellulose polymorphy, crystallite
X-ray powder diffractometer. I. Theoretical foundations. J Appl Crys- size, and the segal crystallinity index. Cellulose 20:583–588.
tallogr 31(6):851–861. 38. Certificate of Analysis. 2008. Standard Reference Material 676a.
25. Cheary RW, Coelho AA, 1998. Axial divergence in a conven- Alumina powder for quantitative analysis by X-ray diffraction.
tional X-ray powder diffractometer. II. Realization and evaluation in Gaithersburg, MD: National Institute of Standards & Technology—
a Fundamental-Parameter profile fitting procedure. J Appl Crystallogr NIST.
31(6):862–868. 39. Oetzel M, Heger G. 1999. Laboratory X-ray powder diffraction:
26. Ciolacu D, Ciolacu F, Popa VI. 2011. Amorphous cellulose— A comparison of different geometries with special attention to the
Structure and characterization. Cellulose Chem Technol 45(1-2):13– usage of the Cu K[alpha] doublet. J Appl Crystallogr 32(4):799–
21. 807.
27. Oh SY, Yoo DI, Shin Y, Kim HC, Kim HY, Chung YS, Park WH, 40. Toby BH. 2006. R factors in Rietveld analysis: How good is good
Youk JH. 2005. Crystalline structure analysis of cellulose treated with enough? Powder Diffr 21:67–70.
sodium hydroxide and carbon dioxide by means of X-ray diffraction and 41. Hill RJ, Flack HD. 1987. The use of the Durbin–Watson d statistic
FTIR spectroscopy. Carbohydr Res 340(15):2376–2391. in Rietveld analysis. J Appl Crystallogr 20:356–361.

DOI 10.1002/jps.23909 De Figueiredo and Ferreira, JOURNAL OF PHARMACEUTICAL SCIENCES 103:1394–1399, 2014

Das könnte Ihnen auch gefallen