The Influence of Polymers on the Supersaturation Potential of Poor and Good Glass Formers

被引:34
作者
Blaabjerg, Lasse, I [1 ]
Grohganz, Holger [1 ]
Lindenberg, Eleanor [2 ]
Lobmann, Korbinian [1 ]
Mullertz, Anettey [1 ]
Rades, Thomas [1 ,3 ]
机构
[1] Univ Copenhagen, Dept Pharm, Univ Pk 2, DK-2100 Copenhagen, Denmark
[2] Idorsia Pharmaceut Ltd, Hegenheimermwattweg 91, CH-4123 Allschwil, Switzerland
[3] Abo Akad Univ, Fac Sci & Engn, Tykistokatu 6A, Turku 20521, Finland
来源
PHARMACEUTICS | 2018年 / 10卷 / 04期
关键词
glass forming ability; amorphous; degree of supersaturation; precipitation inhibitor; pKa; WATER-SOLUBLE POLYMERS; FORMING ABILITY; CRYSTALLIZATION BEHAVIOR; CRYSTAL-GROWTH; DRUG; PRECIPITATION; SOLUBILITY; NUCLEATION; CLASSIFICATION; STABILIZATION;
D O I
10.3390/pharmaceutics10040164
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The increasing number of poorly water-soluble drug candidates in pharmaceutical development is a major challenge. Enabling techniques such as amorphization of the crystalline drug can result in supersaturation with respect to the thermodynamically most stable form of the drug, thereby possibly increasing its bioavailability after oral administration. The ease with which such crystalline drugs can be amorphized is known as their glass forming ability (GFA) and is commonly described by the critical cooling rate. In this study, the supersaturation potential, i.e., the maximum apparent degree of supersaturation, of poor and good glass formers is investigated in the absence or presence of either hypromellose acetate succinate L-grade (HPMCAS-L) or vinylpyrrolidine-vinyl acetate copolymer (PVPVA64) in fasted state simulated intestinal fluid (FaSSIF). The GFA of cinnarizine, itraconazole, ketoconazole, naproxen, phenytoin, and probenecid was determined by melt quenching the crystalline drugs to determine their respective critical cooling rate. The inherent supersaturation potential of the drugs in FaSSIF was determined by a solvent shift method where the respective drugs were dissolved in dimethyl sulfoxide and then added to FaSSIF. This study showed that the poor glass formers naproxen, phenytoin, and probenecid could not supersaturate on their own, however for some drug:polymer combinations of naproxen and phenytoin, supersaturation of the drug was enabled by the polymer. In contrast, all of the good glass formers-cinnarizine, itraconazole, and ketoconazole-could supersaturate on their own. Furthermore, the maximum achievable concentration of the good glass formers was unaffected by the presence of a polymer.
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页数:14
相关论文
共 32 条
[11]   What is the true solubility advantage for amorphous pharmaceuticals? [J].
Hancock, BC ;
Parks, M .
PHARMACEUTICAL RESEARCH, 2000, 17 (04) :397-404
[12]   Maintaining Supersaturation in Aqueous Drug Solutions: Impact of Different Polymers on Induction Times [J].
Ilevbare, Grace A. ;
Liu, Haoyu ;
Edgar, Kevin J. ;
Taylor, Lynne S. .
CRYSTAL GROWTH & DESIGN, 2013, 13 (02) :740-751
[13]   Inhibition of solution crystal growth of ritonavir by cellulose polymers - factors influencing polymer effectiveness [J].
Ilevbare, Grace A. ;
Liu, Haoyu ;
Edgar, Kevin J. ;
Taylor, Lynne S. .
CRYSTENGCOMM, 2012, 14 (20) :6503-6514
[14]  
Jensen Katrine Tarp, 2014, Pharmaceutics, V6, P416, DOI 10.3390/pharmaceutics6030416
[15]   Supersaturating drug delivery systems: The potential of co-amorphous drug formulations [J].
Laitinen, Riikka ;
Lbmann, Korbinian ;
Grohganz, Holger ;
Priemel, Petra ;
Strachan, Clare J. ;
Rades, Thomas .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2017, 532 (01) :1-12
[16]   Nucleation and crystal growth in supersaturated solutions of a model drug [J].
Lindfors, Lennart ;
Forssen, Sara ;
Westergren, Jan ;
Olsson, Ulf .
JOURNAL OF COLLOID AND INTERFACE SCIENCE, 2008, 325 (02) :404-413
[17]   Drug-like properties and the causes of poor solubility and poor permeability [J].
Lipinski, CA .
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS, 2000, 44 (01) :235-249
[18]   The effect of water-soluble polymers on aqueous, solubility of drugs [J].
Loftsson, T ;
Fridriksdottir, H ;
Gudmundsdottir, K .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1996, 127 (02) :293-296
[19]   Effect of composition of simulated intestinal media on the solubility of poorly soluble compounds investigated by design of experiments [J].
Madsen, Cecilie Maria ;
Feng, Kung-I ;
Leithead, Andrew ;
Canfield, Nicole ;
Jorgensen, Soren Astrup ;
Mullertz, Anette ;
Rades, Thomas .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2018, 111 :311-319
[20]   Enhanced in vivo absorption of itraconazole via stabilization of supersaturation following acidic-to-neutral pH transition [J].
Miller, Dave A. ;
DiNunzio, James C. ;
Yang, Wei ;
McGinity, James W. ;
Williams, Robert O., III .
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, 2008, 34 (08) :890-902