Investigation of Drug–Excipient Interactions in Lapatinib Amorphous Solid Dispersions Using Solid-State NMR Spectroscopy
This study investigated the presence of specific drug–excipient interactions in amorphous solid dispersions of lapatinib (LB) and four commonly used pharmaceutical polymers, including Soluplus, polyvinylpyrrolidone vinyl acetate (PVPVA), hydroxypropylmethylcellulose acetate succinate (HPMCAS), and h...
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Published in | Molecular pharmaceutics Vol. 12; no. 3; pp. 857 - 866 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
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American Chemical Society
02.03.2015
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Abstract | This study investigated the presence of specific drug–excipient interactions in amorphous solid dispersions of lapatinib (LB) and four commonly used pharmaceutical polymers, including Soluplus, polyvinylpyrrolidone vinyl acetate (PVPVA), hydroxypropylmethylcellulose acetate succinate (HPMCAS), and hydroxypropylmethylcellulose phthalate (HPMCP). Based on predicted pK a differences, LB was hypothesized to exhibit a specific ionic interaction with HPMCP, and possibly with HPMCAS, while Soluplus and PVPVA were studied as controls without ionizable functionality. Thermal studies showed a single glass transition (T g) for each dispersion, in close agreement with predicted values for Soluplus, PVPVA, and HPMCAS systems. However, the T g values of LB–HPMCP solid dispersions were markedly higher than predicted values, indicating a strong intermolecular interaction between LB and HPMCP. 15N solid-state NMR provided direct spectroscopic evidence for protonation of LB (i.e., salt formation) within the HPMCP solid dispersions. 1H T 1 and 1H T 1ρ relaxation studies of the dispersions supported the ionic interaction hypothesis, and indicated multiple phases in the cases of excess drug or polymer. In addition, the dissolution and stability behavior of each system was examined. Both acidic polymers, HPMCAS and HPMCP, effectively inhibited the crystallization of LB on accelerated stability, likely owing to beneficial strong intermolecular hydrogen and/or specific ionic bonds with the acidic polymers. Soluplus and PVPVA showed poor physical properties on stability and subsequently poor crystallization inhibition. |
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AbstractList | This study investigated the presence of specific drug-excipient interactions in amorphous solid dispersions of lapatinib (LB) and four commonly used pharmaceutical polymers, including Soluplus, polyvinylpyrrolidone vinyl acetate (PVPVA), hydroxypropylmethylcellulose acetate succinate (HPMCAS), and hydroxypropylmethylcellulose phthalate (HPMCP). Based on predicted pKa differences, LB was hypothesized to exhibit a specific ionic interaction with HPMCP, and possibly with HPMCAS, while Soluplus and PVPVA were studied as controls without ionizable functionality. Thermal studies showed a single glass transition (Tg) for each dispersion, in close agreement with predicted values for Soluplus, PVPVA, and HPMCAS systems. However, the Tg values of LB-HPMCP solid dispersions were markedly higher than predicted values, indicating a strong intermolecular interaction between LB and HPMCP. (15)N solid-state NMR provided direct spectroscopic evidence for protonation of LB (i.e., salt formation) within the HPMCP solid dispersions. (1)H T1 and (1)H T1ρ relaxation studies of the dispersions supported the ionic interaction hypothesis, and indicated multiple phases in the cases of excess drug or polymer. In addition, the dissolution and stability behavior of each system was examined. Both acidic polymers, HPMCAS and HPMCP, effectively inhibited the crystallization of LB on accelerated stability, likely owing to beneficial strong intermolecular hydrogen and/or specific ionic bonds with the acidic polymers. Soluplus and PVPVA showed poor physical properties on stability and subsequently poor crystallization inhibition. This study investigated the presence of specific drug–excipient interactions in amorphous solid dispersions of lapatinib (LB) and four commonly used pharmaceutical polymers, including Soluplus, polyvinylpyrrolidone vinyl acetate (PVPVA), hydroxypropylmethylcellulose acetate succinate (HPMCAS), and hydroxypropylmethylcellulose phthalate (HPMCP). Based on predicted pK a differences, LB was hypothesized to exhibit a specific ionic interaction with HPMCP, and possibly with HPMCAS, while Soluplus and PVPVA were studied as controls without ionizable functionality. Thermal studies showed a single glass transition (T g) for each dispersion, in close agreement with predicted values for Soluplus, PVPVA, and HPMCAS systems. However, the T g values of LB–HPMCP solid dispersions were markedly higher than predicted values, indicating a strong intermolecular interaction between LB and HPMCP. 15N solid-state NMR provided direct spectroscopic evidence for protonation of LB (i.e., salt formation) within the HPMCP solid dispersions. 1H T 1 and 1H T 1ρ relaxation studies of the dispersions supported the ionic interaction hypothesis, and indicated multiple phases in the cases of excess drug or polymer. In addition, the dissolution and stability behavior of each system was examined. Both acidic polymers, HPMCAS and HPMCP, effectively inhibited the crystallization of LB on accelerated stability, likely owing to beneficial strong intermolecular hydrogen and/or specific ionic bonds with the acidic polymers. Soluplus and PVPVA showed poor physical properties on stability and subsequently poor crystallization inhibition. |
Author | Yang, Xinghao Lubach, Joseph W Chen, Xin Song, Yang Nie, Haichen Byrn, Stephen |
AuthorAffiliation | Nanjing Normal University GlaxoSmithKline Genentech, Inc Small Molecule Pharmaceutical Sciences Purdue University College of Life Sciences Department of Industrial and Physical Pharmacy |
AuthorAffiliation_xml | – name: Small Molecule Pharmaceutical Sciences – name: Genentech, Inc – name: Nanjing Normal University – name: College of Life Sciences – name: Department of Industrial and Physical Pharmacy – name: Purdue University – name: GlaxoSmithKline |
Author_xml | – sequence: 1 givenname: Yang surname: Song fullname: Song, Yang – sequence: 2 givenname: Xinghao surname: Yang fullname: Yang, Xinghao – sequence: 3 givenname: Xin surname: Chen fullname: Chen, Xin – sequence: 4 givenname: Haichen surname: Nie fullname: Nie, Haichen – sequence: 5 givenname: Stephen surname: Byrn fullname: Byrn, Stephen – sequence: 6 givenname: Joseph W surname: Lubach fullname: Lubach, Joseph W email: lubach.joseph@gene.com |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25585133$$D View this record in MEDLINE/PubMed |
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Cites_doi | 10.1016/S0928-0987(00)00173-1 10.1006/jmra.1994.1208 10.3109/03639049809082722 10.1016/0040-6031(94)80024-3 10.1002/jps.21174 10.1016/j.ssnmr.2006.06.001 10.1016/S0169-409X(01)00098-9 10.1246/bcsj.64.688 10.1021/mp100205g 10.1038/298729a0 10.1021/jf060188r 10.1039/c1ce05183k 10.1002/jps.23358 10.1006/jmre.1999.1896 10.1063/1.1677439 10.1023/A:1015834715152 10.1016/0926-2040(93)90032-I 10.1002/jps.23075 10.1016/j.ejps.2005.04.011 10.1016/0022-2364(77)90260-8 10.1021/ma60061a021 10.1021/mp050004g 10.1021/ja0541332 10.1021/js9601896 10.1007/s11095-011-0655-7 10.1021/jm801331y 10.1023/A:1018967717781 10.1021/mp400498n 10.1016/0022-2364(82)90199-8 |
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Keywords | dissolution rate hydrogen bonding ionic interaction amorphous solid-state NMR salt solid dispersion relaxation lapatinib physical stability |
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References | Yuan X. (ref12/cit12) 2014; 11 Mura P. (ref23/cit23) 1998; 24 Bugay D. E. (ref10/cit10) 1993; 10 Dixon W. T. (ref18/cit18) 1982; 49 Barich D. H. (ref21/cit21) 2006; 30 Li Z. J. (ref30/cit30) 2006; 128 Metz G. (ref15/cit15) 1994; 110 Van den Mooter G. (ref4/cit4) 2001; 12 Kojima T. (ref6/cit6) 2012; 29 Hayashi S. (ref22/cit22) 1991; 64 Laurence C. (ref13/cit13) 2009; 52 Liu H. (ref7/cit7) 2012; 101 Fung B. M. (ref20/cit20) 2000; 142 Stejskal E. O. (ref17/cit17) 1977; 28 Weuts I. (ref9/cit9) 2005; 25 Pines A. (ref16/cit16) 1972; 56 Liu Y. (ref28/cit28) 2006; 54 Wegiel L. A. (ref8/cit8) 2013; 102 Kovacic T. (ref27/cit27) 1994; 231 Chokshi R. J. (ref5/cit5) 2008; 97 Forster A. (ref26/cit26) 2003; 58 Couchman P. R. (ref25/cit25) 1978; 11 Oksanen C. A. (ref3/cit3) 1990; 7 Yu L. (ref2/cit2) 2001; 48 Song Z. (ref19/cit19) 1993; 2 Couchman P. R. (ref24/cit24) 1982; 298 Hancock B. C. (ref1/cit1) 1997; 86 Van Eerdenbrugh B. (ref14/cit14) 2011; 13 Pham T. N. (ref11/cit11) 2010; 7 Gupta P. (ref29/cit29) 2005; 2 |
References_xml | – volume: 12 start-page: 261 issue: 3 year: 2001 ident: ref4/cit4 publication-title: Eur. J. Pharm. Sci. doi: 10.1016/S0928-0987(00)00173-1 contributor: fullname: Van den Mooter G. – volume: 58 start-page: 838 issue: 11 year: 2003 ident: ref26/cit26 publication-title: Pharmazie contributor: fullname: Forster A. – volume: 110 start-page: 219 issue: 2 year: 1994 ident: ref15/cit15 publication-title: J. Magn. Reson., Ser. A doi: 10.1006/jmra.1994.1208 contributor: fullname: Metz G. – volume: 24 start-page: 747 issue: 8 year: 1998 ident: ref23/cit23 publication-title: Drug Dev. Ind. Pharm. doi: 10.3109/03639049809082722 contributor: fullname: Mura P. – volume: 231 start-page: 215 issue: 1 year: 1994 ident: ref27/cit27 publication-title: Thermochim. Acta doi: 10.1016/0040-6031(94)80024-3 contributor: fullname: Kovacic T. – volume: 97 start-page: 2286 issue: 6 year: 2008 ident: ref5/cit5 publication-title: J. Pharm. Sci. doi: 10.1002/jps.21174 contributor: fullname: Chokshi R. J. – volume: 30 start-page: 125 issue: 3 year: 2006 ident: ref21/cit21 publication-title: Solid State Nucl. Magn. Reson. doi: 10.1016/j.ssnmr.2006.06.001 contributor: fullname: Barich D. H. – volume: 48 start-page: 27 issue: 1 year: 2001 ident: ref2/cit2 publication-title: Adv. Drug Delivery Rev. doi: 10.1016/S0169-409X(01)00098-9 contributor: fullname: Yu L. – volume: 64 start-page: 688 issue: 2 year: 1991 ident: ref22/cit22 publication-title: Bull. Chem. Soc. Jpn. doi: 10.1246/bcsj.64.688 contributor: fullname: Hayashi S. – volume: 7 start-page: 1667 issue: 5 year: 2010 ident: ref11/cit11 publication-title: Mol. Pharmaceutics doi: 10.1021/mp100205g contributor: fullname: Pham T. N. – volume: 298 start-page: 729 issue: 5876 year: 1982 ident: ref24/cit24 publication-title: Nature doi: 10.1038/298729a0 contributor: fullname: Couchman P. R. – volume: 54 start-page: 5701 issue: 16 year: 2006 ident: ref28/cit28 publication-title: J. Agric. Food Chem. doi: 10.1021/jf060188r contributor: fullname: Liu Y. – volume: 13 start-page: 6171 issue: 20 year: 2011 ident: ref14/cit14 publication-title: CrystEngComm doi: 10.1039/c1ce05183k contributor: fullname: Van Eerdenbrugh B. – volume: 102 start-page: 171 issue: 1 year: 2013 ident: ref8/cit8 publication-title: J. Pharm. Sci. doi: 10.1002/jps.23358 contributor: fullname: Wegiel L. A. – volume: 142 start-page: 97 issue: 1 year: 2000 ident: ref20/cit20 publication-title: J. Magn. Reson. doi: 10.1006/jmre.1999.1896 contributor: fullname: Fung B. M. – volume: 56 start-page: 1776 issue: 4 year: 1972 ident: ref16/cit16 publication-title: J. Chem. Phys. doi: 10.1063/1.1677439 contributor: fullname: Pines A. – volume: 7 start-page: 654 issue: 6 year: 1990 ident: ref3/cit3 publication-title: Pharm. Res. doi: 10.1023/A:1015834715152 contributor: fullname: Oksanen C. A. – volume: 2 start-page: 143 issue: 3 year: 1993 ident: ref19/cit19 publication-title: Solid State Nucl. Magn. Reson. doi: 10.1016/0926-2040(93)90032-I contributor: fullname: Song Z. – volume: 101 start-page: 2204 issue: 6 year: 2012 ident: ref7/cit7 publication-title: J. Pharm. Sci. doi: 10.1002/jps.23075 contributor: fullname: Liu H. – volume: 25 start-page: 387 issue: 4 year: 2005 ident: ref9/cit9 publication-title: Eur. J. Pharm. Sci. doi: 10.1016/j.ejps.2005.04.011 contributor: fullname: Weuts I. – volume: 28 start-page: 105 issue: 1 year: 1977 ident: ref17/cit17 publication-title: J. Magn. Reson. (1969–1992) doi: 10.1016/0022-2364(77)90260-8 contributor: fullname: Stejskal E. O. – volume: 11 start-page: 117 issue: 1 year: 1978 ident: ref25/cit25 publication-title: Macromolecules doi: 10.1021/ma60061a021 contributor: fullname: Couchman P. R. – volume: 2 start-page: 384 issue: 5 year: 2005 ident: ref29/cit29 publication-title: Mol. Pharmaceutics doi: 10.1021/mp050004g contributor: fullname: Gupta P. – volume: 128 start-page: 8199 issue: 25 year: 2006 ident: ref30/cit30 publication-title: J. Am. Chem. Soc. doi: 10.1021/ja0541332 contributor: fullname: Li Z. J. – volume: 86 start-page: 1 issue: 1 year: 1997 ident: ref1/cit1 publication-title: J. Pharm. Sci. doi: 10.1021/js9601896 contributor: fullname: Hancock B. C. – volume: 29 start-page: 2777 issue: 10 year: 2012 ident: ref6/cit6 publication-title: Pharm. Res. doi: 10.1007/s11095-011-0655-7 contributor: fullname: Kojima T. – volume: 52 start-page: 4073 issue: 14 year: 2009 ident: ref13/cit13 publication-title: J. Med. Chem. doi: 10.1021/jm801331y contributor: fullname: Laurence C. – volume: 10 start-page: 317 issue: 3 year: 1993 ident: ref10/cit10 publication-title: Pharm. Res. doi: 10.1023/A:1018967717781 contributor: fullname: Bugay D. E. – volume: 11 start-page: 329 issue: 1 year: 2014 ident: ref12/cit12 publication-title: Mol. Pharmaceutics doi: 10.1021/mp400498n contributor: fullname: Yuan X. – volume: 49 start-page: 341 issue: 2 year: 1982 ident: ref18/cit18 publication-title: J. Magn. Reson. (1969–1992) doi: 10.1016/0022-2364(82)90199-8 contributor: fullname: Dixon W. T. |
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Snippet | This study investigated the presence of specific drug–excipient interactions in amorphous solid dispersions of lapatinib (LB) and four commonly used... This study investigated the presence of specific drug-excipient interactions in amorphous solid dispersions of lapatinib (LB) and four commonly used... |
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SubjectTerms | Biological Availability Biopharmaceutics Crystallization Drug Carriers - chemistry Drug Stability Excipients Humans Hydrogen Bonding Magnetic Resonance Spectroscopy Methylcellulose - analogs & derivatives Methylcellulose - chemistry Polyethylene Glycols - chemistry Polyvinyls - chemistry Povidone - analogs & derivatives Povidone - chemistry Quinazolines - administration & dosage Quinazolines - chemistry Quinazolines - pharmacokinetics Solubility |
Title | Investigation of Drug–Excipient Interactions in Lapatinib Amorphous Solid Dispersions Using Solid-State NMR Spectroscopy |
URI | http://dx.doi.org/10.1021/mp500692a https://www.ncbi.nlm.nih.gov/pubmed/25585133 https://search.proquest.com/docview/1660433330 |
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