Polymer swelling, drug mobilization and drug recrystallization in hydrating solid dispersion tablets studied by multinuclear NMR microimaging and spectroscopy

Molecular Pharmaceutics

Volumn 8, Issue 4, 2011, Pages 1247-1256

  Dahlberg, Carina ^a,b   Dvinskikh, Sergey V ^a   Schuleit, Michael ^c   Furó, István ^a  

^a ROYAL INSTITUTE OF TECHNOLOGY   (Sweden)

^b NOVARTIS PHARMA AG   (Switzerland)

^c INSTITUTE FOR SURFACE CHEMISTRY   (Sweden)

Author keywords

amorphous drug nanoparticles; hydroxypropyl methylcellulose HPMC; in situ monitoring; NMR imaging; particle size; recrystallization kinetics

Indexed keywords

FLUTAMIDE; NANOPARTICLE; POLYMER;

ARTICLE; CRYSTALLIZATION; DRUG FORMULATION; DRUG SOLUBILITY; DRUG STRUCTURE; FLUORINE NUCLEAR MAGNETIC RESONANCE; IMAGING SYSTEM; INTERMETHOD COMPARISON; NUCLEAR MAGNETIC RESONANCE IMAGING; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRIORITY JOURNAL; SOLID PHASE SYNTHESIS; TABLET DISINTEGRATION;

CRYSTALLIZATION; FLUTAMIDE; KINETICS; MOLECULAR STRUCTURE; NANOPARTICLES; NUCLEAR MAGNETIC RESONANCE, BIOMOLECULAR; PARTICLE SIZE; POLYMERS; X-RAY DIFFRACTION;

EID: 79961049302     PISSN: 15438384     EISSN: 15438392     Source Type: Journal    
DOI: 10.1021/mp200051e     Document Type: Article

References (88)

1. Fahr, A.; Liu, X. Drug delivery strategies for poorly water-soluble drugs Expert Opin. Drug Delivery 2007, 4 (4) 403-416 (Pubitemid 47249138)
2. Saleki-Gerhardt, A.; Zografi, G. Non-isothermal and isothermal crystallization of sucrose from the amorphous state Pharm. Res. 1994, 11 (8) 1166-1173 (Pubitemid 24259858)
3. Hancock, B. C.; Zografi, G. Characteristics and significance of the amorphous state in pharmaceutical systems J. Pharm. Sci. 1996, 86 (1) 1-12
4. Yu, L. Amorphous pharmaceutical solids: preparation, characterization and stabilization Adv. Drug Delivery Rev. 2001, 48 (1) 27-42 (Pubitemid 32454482)
5. Urbanetz, N. A.; Lippold, B. C. Solid dispersions of nimodipine and polyethylene glycol 2000: dissolution properties and physico-chemical characterisation Eur. J. Pharm. Sci. 2005, 59 (1) 107-118 (Pubitemid 39573442)
6. Chaubal, M. V.; Popescu, C. Conversion of nanosuspensions into dry powders by spray drying: A case study Pharm. Res. 2008, 25 (10) 2302-2308
7. Chiou, W. L.; Riegelman, S. Pharmaceutical applications of solid dispersion systems J. Pharm. Sci. 1971, 60 (9) 1281-1302
8. Serajuddin, A. T. M. Solid dispersion of poorly water-soluble drugs: Early promises, subsequent problems, and recent breakthroughs J. Pharm. Sci. 1999, 88 (10) 1058-1066
9. Leuner, C.; Dressman, J. Improving drug solubility for oral delivery using solid dispersions Eur. J. Pharm. Sci. 2000, 50 (1) 47-60 (Pubitemid 30326688)
10. Vasconcelos, T.; Sarmento, B.; Costa, P. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs Drug Discovery Today 2007, 12 (23-24) 1068-1075 (Pubitemid 350186132)
11. Chow, K.; Tong, H. H. Y.; Lum, S.; Chow, A. H. L. Engineering of pharmaceutical materials: an industrial perspective J. Pharm. Sci. 2008, 97 (8) 2855-2877
12. Murphy, D.; Rodríguez-Cintrón, F.; Langevin, B.; Kelly, R. C.; Rodríguez-Hornedo, N. Solution-mediated phase transformation of anhydrous to dihydrate carbamazepine and the effect of lattice disorder Int. J. Pharm. 2002, 246 (1-2) 121-134 (Pubitemid 35247985)
13. Greco, K.; Bogner, R. Crystallization of amorphous indomethacin during dissolution: Effect of processing and annealing Mol. Pharmaceutics 2010, 7 (5) 1406-1418
14. Ghebremeskel, A. N.; Vernavarapu, C.; Lodaya, M. Use of surfactants as plasticizers in preparing solid dispersions of poorly soluble API: Selection of polymer-surfactant combinations using solubility parameters and testing the processability Int. J. Pharm. 2007, 328 (2) 119-129 (Pubitemid 44895482)
15. g J. Pharm. Sci. 2008, 97 (10) 4498-4515
16. Andronis, V.; Yoshioka, M.; Zografi, G. Effects of sorbed water on the crystallization of indomethacin from the amorphous state J. Pharm. Sci. 1997, 86 (3) 346-351
17. Papageorgiou, G. Z.; Bikiaris, D.; Karavas, E.; Politis, S.; Docoslis, A.; Park, Y.; Stergiou, A.; Georgarakis, E. Effect of physical state and particle size distribution on dissolution enhancement of nimodipine/PEG solid dispersions prepared by melt mixing and solvent evaporation AAPS J. 2006, 8 (4) 623-631
18. Docoslis, A.; Huszarik, K. L.; Papageorgiou, G. Z.; Bikiaris, D.; Stergiou, A.; Georgarakis, E. Characterization of the distribution, polymorphism, and stability of nimodipine in its solid dispersions in polyethylene glycol by micro-Raman spectroscopy and powder X-ray diffraction AAPS J. 2007, 9 (3) 361-370
19. Karavas, E.; Georgarakis, E.; Sigalas, M. P.; Avgoustakis, K.; Bikiaris, D. Investigation of the release mechanism of a sparingly water-soluble drug from solid dispersions in hydrophilic carriers based on physical state of drug, particle size distribution and drug-polymer interactions Eur. J. Pharm. Sci. 2007, 66 (3) 334-347 (Pubitemid 46778978)
20. Karavas, E.; Georgarakis, M.; Docoslis, A.; Bikiaris, D. Combining SEM, TEM, and micro-Raman techniques to differentiate between the amorphous molecular level dispersions and nanodispersions of a poorly water-soluble drug within a polymer matrix Int. J. Pharm. 2007, 340, 76-83 (Pubitemid 47044963)
21. Zhang, J.; Bunker, M.; Chen, X.; Parker, A. P.; Patel, N.; Roberts, C. J. Nanoscale thermal analysis of pharmaceutical solid dispersions Int. J. Pharm. 2009, 380, 170-173
22. Newman, A.; Engers, D.; Bates, S.; Ivanisevic, I.; Kelly, R. C.; Zografi, G. Characterization of Amorphous API:Polymer Mixtures Using X-Ray Powder Diffraction J. Pharm. Sci. 2008, 97 (11) 4840-4856
23. Ivanisevic, I.; Bates, S.; Chen, P. Novel Methods for the Assessment of Miscibility of Amorphous Drug-Polymer Dispersions J. Pharm. Sci. 2009, 98 (9) 3373-3386
24. Moore, M. D.; Shi, Z. Q.; Wildfong, P. L. D. Structural Interpretation in Composite Systems Using Powder X-ray Diffraction: Applications of Error Propagation to the Pair Distribution Function Pharm. Res. 2010, 27 (12) 2624-2632
25. Markovich, R. J.; Evans, C. A.; Coscolluela, C. B.; Zibas, S. A.; Rosen, J. Spectroscopic identification of an amorphous-to-crystalline drug transition in a solid dispersion SCH 48461 capsule formulation J. Pharm. Biomed. Anal. 1997, 16 (4) 661-673 (Pubitemid 28044198)
26. Tobyn, M.; Brown, J.; Dennis, A. B.; Fakes, M.; Gao, Q.; Gamble, J.; Khimyak, Y. Z.; McGeorge, G.; Patel, C.; Sinclair, W.; Timmins, P.; Yin, S. Amorphous Drug-PVP Dispersions: Application of Theoretical, Thermal and Spectroscopic Analytical Techniques to the Study of a Molecule With Intermolecular Bonds in Both the Crystalline and Pure Amorphous State J. Pharm. Sci. 2009, 98 (9) 3456-3468
27. Malaj, L.; Censi, R.; Mozzicafreddo, M.; Pellegrino, L.; Angeletti, M.; Gobetto, R.; Di Martino, P. Influence of relative humidity on the interaction between different aryl propionic acid derivatives and poly(vinylpyrrolydone) K30: Evaluation of the effect on drug bioavailability Int. J. Pharm. 2010, 398 (1-2) 61-72
28. Pham, T. N.; Watson, S. A.; Edwards, A. J.; Chavda, M.; Clawson, J. S.; Strohmeier, M.; Vogt, F. G. Analysis of Amorphous Solid Dispersions Using 2D Solid-State NMR and H-1 T-1 Relaxation Measurements Mol. Pharmaceutics 2010, 7 (5) 1667-1691
29. Vogt, F. G.; Clawson, J. S.; Strohmeier, M.; Edwards, A. J.; Pham, T. N.; Watson, S. A. Solid-State NMR Analysis of Organic Cocrystals and Complexes Cryst. Growth Des. 2009, 9 (2) 921-937
30. Gladden, L. F. Nuclear magnetic resonance in chemical engineering: Principles and applications Chem. Eng. Sci. 1994, 49 (20) 3339-3408
31. Blümich, B. NMR Imaging of Materials; Oxford Univ. Press: New York, 2000.
32. Bowtell, R.; Sharp, J. C.; Peters, A.; Mansfield, P.; Rajabi-Siahboomi, A. R.; Davies, M. C.; Melia, C. D. NMR microscopy of hydrating hydrophilic matrix pharmaceutical tablets Magn. Reson. Imaging 1994, 12 (2) 361
33. Rajabi-Siahboomi, A. R.; Bowtell, R. W.; Mansfield, P.; Henderson, A.; Davies, M. C.; Melia, C. D. Structure and behaviour in hydrophilic matrix sustained release dosage forms: 2. NMR-imaging studies of dimensional changes in the gel layer and core of HPMC tablets undergoing hydration J. Controlled Release 1994, 31 (2) 121
34. Fahie, B. J.; Nangia, A.; Chopra, S. K.; Fyfe, C. A.; Grondey, H.; Blazek, A. Use of NMR imaging in the optimization of a compression-coated regulated release system J. Controlled Release 1998, 51 (2-3) 179-184 (Pubitemid 28252869)
35. Fyfe, C. A.; Blazek, A. I. Investigation of hydrogel formation from hydroxypropylmethylcellulose (HPMC) by NMR spectroscopy and NMR imaging techniques Macromolecules 1997, 30 (20) 6230-6237 (Pubitemid 127574394)
36. Harding, S.; Baumann, H.; Gren, T.; Seo, A. NMR microscopy of the uptake, distribution and mobility of dissolution media in small, sub-millimetre drug delivery systems J. Controlled Release 2000, 66 (1) 81-99 (Pubitemid 30116687)
37. Malveau, C.; Baille, W. E.; Zhu, X. X.; Marchessault, R. H. NMR imaging of high-amylose starch tablets. 2. Effect of tablet size Biomacromolecules 2002, 3 (6) 1249-1254 (Pubitemid 35423022)
38. Richardson, J. C.; Bowtell, R. W.; Mader, K.; Melia, C. D. Pharmaceutical applications of magnetic resonance imaging (MRI) Adv. Drug Delivery Rev. 2005, 57 (8) 1191
39. Therien-Aubin, H.; Baille, W. E.; Zhu, X. X.; Marchessault, R. H. Imaging of high-amylose starch tablets. 3. Initial diffusion and temperature effects Biomacromolecules 2005, 6 (6) 3367-3372 (Pubitemid 41764100)
40. Tritt-Goc, J.; Kowalczuk, J. Spatially resolved solvent interaction with glassy HPMC polymers studied by magnetic resonance microscopy Solid State Nucl. Magn. Reson. 2005, 28 (2-4) 250
41. Tritt-Goc, J.; Pislewski, N. Magnetic resonance imaging study of the swelling kinetics of hydroxypropylmethylcellulose (HPMC) in water J. Controlled Release 2002, 80 (1-3) 79-86 (Pubitemid 34273750)
42. Broadbent, A. L.; Fell, R. J.; Codd, S. L.; Lightley, K. A.; Konagurthu, S.; Koehler-King, D. G.; Seymour, J. D. Magnetic resonance imaging and relaxometry to study water transport mechanisms in a commercially available gastrointestinal therapeutic system (GITS) tablet Int. J. Pharm. 2010, 397 (1-2) 27-35
43. Chen, Y. Y.; Hughes, L. P.; Gladden, L. F.; Mantle, M. D. Quantitative ultra-fast MRI of HPMC swelling and dissolution J. Pharm. Sci. 2010, 99 (8) 3462-3472
44. Laity, P. R.; Mantle, M. D.; Gladden, L. F.; Cameron, R. E. Magnetic resonance imaging and X-ray microtomography studies of a gel-forming tablet formulation Eur. J. Pharm. Biopharm. 2010, 74 (1) 109-119
45. Mikac, U.; Sepe, A.; Kristl, J.; Baumgartner, S. A new approach combining different MRI methods to provide detailed view on swelling dynamics of xanthan tablets influencing drug release at different pH and ionic strength J. Controlled Release 2010, 145 (3) 247-256
46. Nott, K. P. Magnetic resonance imaging of tablet dissolution Eur. J. Pharm. Biopharm. 2010, 74 (1) 78-83
47. Dahlberg, C.; Millqvist-Fureby, A.; Schuleit, M.; Furó, I. Relationships between solid dispersion preparation process, particle size and drug release-an NMR and NMR microimaging study Eur. J. Pharm. Biopharm. 2010, 76 (2) 311-319
48. 1H NMR and NMR microimaging study J. Controlled Release 2007, 122 (2) 199-205 (Pubitemid 47361408)
49. Emid, S.; Creyghton, J. H. N. High resolution NMR imaging in solids Physica B+C 1985, 128 (1) 81-83 (Pubitemid 15464352)
50. Gravina, S.; Cory, D. G. Sensitivity and resolution of constant-time imaging J. Magn. Reson., Ser. B 1994, 104 (1) 53-61
51. Hyde, T. M.; Gladden, L. F. Simultaneous measurement of water and polymer concentration profiles during swelling of poly(ethylene oxide) using magnetic resonance imaging Polymer 1998, 39 (4) 811
52. 2* nuclei with single-point imaging (SPI) methods J. Magn. Reson. 1998, 135 (1) 156-164 (Pubitemid 128450699)
53. 19F-NMR for assessing the molecular mobility of flufenamic acid in solid dispersions Chem. Pharm. Bull. 2009, 57 (1) 61-64
54. Sternal, R.; Nugara, N. Flutamide Anal. Profiles Drug Subst. Excipients 2001, 27, 115-157 (Pubitemid 33805288)
55. 1 spin-lattice relaxation and a cross-polarization dynamics study of the molecular motions of a side-chain liquid-crystalline polymer Macromolecules 1992, 25 (9) 2341-2350
56. 13C CP/MAS NMR Pharm. Res. 1998, 15 (9) 1425-1433 (Pubitemid 28427932)
57. 1H NMR relaxation times J. Pharm. Sci. 2000, 89 (3) 408-416 (Pubitemid 30152440)
58. 13C nuclear magnetic resonance relaxation time and the relaxation time obtained from the heating rate dependence of the glass transition temperature J. Pharm. Sci. 2001, 90 (6) 798-806 (Pubitemid 32536774)
59. Murakami, M.; Ishida, H.; Kaji, H.; Horii, F. Solid-state C-13 NMR studies of the structure and chain conformation of thermotropic liquid crystalline polyether crystallized from the liquid crystalline glassy phase Polym. J. 2004, 36 (5) 403-412
60. Masuda, K.; Tabata, S.; Sakata, Y.; Hayase, T.; Yonemochi, E.; Terada, K. Comparison of molecular mobility in the glassy state between amorphous indomethacin and salicin based on spin-lattice relaxation times Pharm. Res. 2005, 22 (5) 797-805 (Pubitemid 40768593)
61. Apperley, D. C.; Forster, A. H.; Fournier, R.; Harris, R. K.; Hodgkinson, P.; Lancaster, R. W.; Rades, T. Characterisation of indomethacin and nifedipine using variable-temperature solid-state NMR Magn. Reson. Chem. 2005, 43 (11) 881-892 (Pubitemid 41512842)
62. Lubach, J. W.; Xu, D. W.; Segmuller, B. E.; Munson, E. J. Investigation of the effects of pharmaceutical processing upon solid-state NMR relaxation times and implications to solid-state formulation stability J. Pharm. Sci. 2007, 96 (4) 777-787 (Pubitemid 46657868)
63. Adam-Berret, M.; Riaublanc, A.; Rondeau-Mouro, C.; Mariette, F. Effects of crystal growth and polymorphism of triacylglycerols on NMR relaxation parameters. 1. Evidence of a relationship between crystal size and spin-lattice relaxation time Cryst. Growth Des. 2009, 9 (10) 4273-4280
64. 19F NMR methods for studying biomembranes Prog. Nucl. Magn. Reson. Spectrosc. 2005, 46 (1) 1-21 (Pubitemid 40357060)
65. Emid, S.; Baarda, R. J.; Smidt, J.; Wind, R. A. Influence of symmetry-restricted spin diffusion on spin-lattice relaxation of molecular groups in solids Physica B+C 1978, 93 (3) 327-343
66. Torchia, D. A.; Szabo, A. Spin-lattice relaxation in solids J. Magn. Reson. 1982, 49 (1) 107-121
67. Abragam, A. Principles of Nuclear Magnetism; Oxford Univ. Press: Oxford, 1961.
68. Cowan, B. Nuclear Magnetic Resonance and Relaxation; Cambridge Univ. Press: 1997.
69. Wang, S. C.; Tsa, H. K. Ion migration through a polymer solution: Microviscosity Macromolecules 2003, 36 (24) 9128-9134
70. Cheong, L. W. S.; Heng, P. W. S.; Wong, L. F. Relationship between polymer viscosity and drug release from a matrix system Pharm. Res. 1992, 9 (11) 1510-1514
71. ShinEtsu. Pharmacoat; Cellulose and pharmaceutical excipient department: Tokyo, 2004.
72. Powles, J. G.; Mansfield, P. Double-pulse nuclear-resonance transients in solids Phys. Lett. 1962, 2, 56-59
73. Beckmann, P. A.; Rosenberg, J.; Nordstrom, K.; Mallory, C. W.; Mallory, F. B. CF3 rotation in 3-(trifluoromethyl)phenanthrene: Solid state F-19 and H-1 NMR relaxation and Bloch-Wangsness-Redfield theory J. Phys. Chem. A 2006, 110 (11) 3947-3953
74. Siepe, S.; Herrmann, W.; Borchert, H. H.; Lueckel, B.; Kramer, A.; Ries, A.; Gurny, R. Microenvironmental pH and microviscosity inside pH-controlled matrix tablets: An EPR imaging study J. Controlled Release 2006, 112 (1) 72-78
75. Kowalewski, J.; Mäler, L. Nuclear Spin Relaxation in Liquids; CRC Press: Boca Raton, 2006.
76. Wennerström, H.; Lindblom, G.; Lindman, B. Theoretical aspects on the NMR of quadrupolar ionic nuclei in micellar solutions and amphiphilic liquid crystals Chem. Scr. 1974, 6, 97-103
77. 1 J. Am. Chem. Soc. 1979, 101, 6860-6864 (Pubitemid 10437043)
78. Lipari, G.; Szabo, A. Model-free approach to the interpretation of nuclear magnetic resonance relaxation in macromolecules. 1. Theory and range of validity J. Am. Chem. Soc. 1982, 17, 4546-4559
79. Matson, G. B. Methyl NMR relaxation due to dipolar interactions J. Chem. Phys. 1975, 65, 4147-4154
80. Werbelow, L. G.; Marshall, A. G. Internal rotation and nonexponential methyl nuclear relaxation for macromolecules J. Magn. Reson. 1973, 11 (2) 299-313
81. Katzhendler, I.; Mäder, K.; Friedman, M. Structure and hydration properties of hydroxypropyl methylcellulose matrices containing naproxen and naproxen sodium Int. J. Pharm. 2000, 200 (2) 161-179 (Pubitemid 30364903)
82. Dahlberg, C.; Millqvist-Fureby, A.; Schuleit, M.; Furó, I. Polymer-drug interactions and wetting of solid dispersions Eur. J. Pharm. Sci. 2010, 39 (1-3) 125-133
83. Penn, R. L.; Banfield, J. F. Formation of rutile nuclei at anatase {112} twin interfaces and the phase transformation mechanism in nanocrystalline titania Am. Mineral. 1999, 84 (5-6) 871-876 (Pubitemid 29497011)
84. Zhang, H. Z.; Banfield, J. F. Phase transformation of nanocrystalline anatase-to-rutile via combined interface and surface nucleation J. Mater. Res. 2000, 15 (2) 437-448 (Pubitemid 34567024)
85. Zhang, H. Z.; Banfield, J. F. Polymorphic transformations and particle coarsening in nanocrystalline titania ceramic powders and membranes J. Phys. Chem. C 2007, 111 (18) 6621-6629 (Pubitemid 46826417)
86. Colfen, H.; Qi, L. M. A systematic examination of the morphogenesis of calcium carbonate in the presence of a double-hydrophilic block copolymer Chem.-Eur. J. 2001, 7 (1) 106-116 (Pubitemid 33667569)
87. Judat, B.; Kind, M. Morphology and internal structure of barium sulfate-derivation of a new growth mechanism J. Colloid Interface Sci. 2004, 269 (2) 341-353 (Pubitemid 37491163)
88. 3 and control of particle formation by polyelectrolytes Faraday Discuss. 2007, 136, 265-277