Utility of Films to Anticipate Effect of Drug Load and Polymer on Dissolution Performance from Tablets of Amorphous Itraconazole Spray-Dried Dispersions

被引:18
作者
Honick, Moshe [1 ]
Sarpal, Kanika [2 ]
Alayoubi, Alaadin [3 ]
Zidan, Ahmed [3 ]
Hoag, Stephen W. [1 ]
Hollenbeck, Robert G. [1 ]
Munson, Eric J. [2 ,4 ]
Polli, James E. [1 ]
机构
[1] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA
[2] Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY 40536 USA
[3] US FDA, Silver Spring, MD 20993 USA
[4] Purdue Univ, Coll Pharm, Dept Ind & Phys Pharm, W Lafayette, IN 47907 USA
关键词
amorphous solid dispersion; itraconazole; spray drying; dissolution; hypromellose acetate succinate; GLASS-TRANSITION TEMPERATURE; SOLID-STATE CHARACTERIZATION; PHYSICAL STABILITY; PHASE-SEPARATION; CRYSTALLIZATION; IMPACT; BIOAVAILABILITY; MISCIBILITY; SOLUBILITY; INSIGHTS;
D O I
10.1208/s12249-019-1541-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Because spray-dried dispersion (SDD) performance depends on polymer selection and drug load, time- and resource-sparing methods to screen drug/polymer combinations before spray drying are desirable. The primary objective was to assess the utility of films to anticipate the effects of drug load and polymer grade on dissolution performance of tablets containing SDDs of itraconazole (ITZ). A secondary objective was to characterize the solid-state attributes of films and SDDs to explain drug load and polymer effects on dissolution performance. SDDs employed three different grades of hypromellose acetate succinate (i.e., either HPMCAS-L, HPMCAS-M, or HPMCAS-H). Solid-state characterization employed differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and solid-state nuclear magnetic resonance (ssNMR) spectroscopy. Results indicate that films correctly anticipated the effects of drug load and polymer on dissolution performance. The best dissolution profiles were observed under the following conditions: 20% drug loading performed better than 30% for both films and SDDs, and the polymer grade rank order was HPMCAS-L > HPMCAS-M > HPMCAS-H for both films and SDDs. No dissolution was detected from films or SDDs containing HPMCAS-H. Solid-state characterization revealed percent crystallinity and phase miscibility as contributing factors to dissolution, but were not the sole factors. Amorphous content in films varied with drug load (10% > 20% > 30%) and polymer grades (HPMCAS-L > HPMCAS-M > HPMCAS-H), in agreement with dissolution. In conclusion, films anticipated the rank-order effects of drug load and polymer grade on dissolution performance from SDDs of ITZ, in part through percent crystallinity and phase miscibility influences.
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页数:13
相关论文
共 37 条
[31]   Physicochemical Properties of the Amorphous Drug, Cast Films, and Spray Dried Powders to Predict Formulation Probability of Success for Solid Dispersions: Etravirine [J].
Weuts, Ilse ;
Van Dycke, Frederic ;
Voorspoels, Jody ;
De Cort, Steve ;
Stokbroekx, Sigrid ;
Leemans, Ruud ;
Brewster, Marcus E. ;
Xu, Dawei ;
Segmuller, Brigitte ;
Turner, Ya Tsz A. ;
Roberts, Clive J. ;
Davies, Martyn C. ;
Qi, Sheng ;
Craig, Duncan Q. M. ;
Reading, Mike .
JOURNAL OF PHARMACEUTICAL SCIENCES, 2011, 100 (01) :260-274
[32]  
Williams III R.O., 2016, AAPS ADV PHARM SCI S, V22
[33]   Development of orodispersible polymer films containing poorly water soluble active pharmaceutical ingredients with focus on different drug loadings and storage stability [J].
Woertz, Christina ;
Kleinebudde, Peter .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2015, 493 (1-2) :134-145
[34]   Development of orodispersible polymer films with focus on the solid state characterization of crystalline loperamide [J].
Woertz, Christina ;
Kleinebudde, Peter .
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 2015, 94 :52-63
[35]   Effect of Temperature and Moisture on the Physical Stability of Binary and Ternary Amorphous Solid Dispersions of Celecoxib [J].
Xie, Tian ;
Taylor, Lynne S. .
JOURNAL OF PHARMACEUTICAL SCIENCES, 2017, 106 (01) :100-110
[36]  
YU TY, 1990, PROG POLYM SCI, V15, P825
[37]   Crystallization of Itraconazole Polymorphs from Melt [J].
Zhang, Shuai ;
Lee, Thomas W. Y. ;
Chow, Albert H. L. .
CRYSTAL GROWTH & DESIGN, 2016, 16 (07) :3791-3801