Mechanistic characterization of bilayer tablet formulations

被引:38
作者
Akseli, Ilgaz [1 ]
Abebe, Admassu [2 ]
Sprockel, Omar [2 ]
Cuitino, Alberto M. [1 ]
机构
[1] Rutgers State Univ, Dept Mech & Aerosp Engn, Piscataway, NJ 08854 USA
[2] Bristol Myers Squibb Co, Drug Prod & Sci Technol, New Brunswick, NJ USA
关键词
Bilayer tablet; Axial tensile strength; Bilayer interface; Bonding; Delamination; DIRECT COMPRESSION; X-RAY; STRENGTH; RELEASE; TOMOGRAPHY; MATRICES;
D O I
10.1016/j.powtec.2012.05.048
中图分类号
TQ [化学工业];
学科分类号
0817 ;
摘要
The interest in bilayer tablet as an oral immediate-release/controlled-release system has substantially increased in the past decade. However, during the production of such tablets, lack of sufficient bonding and adhesion at interfaces between adjacent layers is compromising the mechanical integrity and performance of the final solid dosage form. In this study, bilayer tablets of the widely used excipient microcrystalline cellulose in the form of Avicel 102 and pregelatinized starch were formed with different pre-compression (2 kN, 4 kN, 6 kN, 8 kN) and final compression (6 kN, 10 kN, 14 kN, 18 kN) forces to quantitatively characterize the strength (sigma) of the interface and the compacted adjacent layers. Bilayer tablets were axially debonded (i.e., separation of adjacent layers that are subjected to axial loading) until fracture and axial tensile strength values were determined. It was observed that when the first layer was compressed to a low porosity, the bonding with the second layer became difficult and it was not possible to produce intact bilayer tablets (sigma(layer)>sigma(interface)). It has been demonstrated that the material response of the constrained MCC particles to an applied initial compression force within the initial compacted layer have a detrimental effect on the resistance to fracture of a bilayer tablet. The mechanism of failure at the interface or at the individual layers was also studied. Different fracture patterns, namely, clear layer break, half-half break, cap-shape break, and clear interface break were observed as a function of various initial and final compression forces. X-ray micro-computed tomography (mu CT) was utilized to examine the influence of localized density distribution on the delamination (layer separation) phenomena of bilayer tablets. It has been shown that once the magnitude of the applied final layer compaction stress greatly exceeds the initial layer compaction stress, the tablet catastrophically fails at the initial layer not at the interface (sigma(layer)<sigma(interface)). The results of this study point out that the measurement of the interfacial strength provides insight into some of the major complications of bilayer tablets. (C) 2012 Elsevier B.V. All rights reserved.
引用
收藏
页码:30 / 36
页数:7
相关论文
共 19 条
[1]   A flexible technology for modified release of drugs: multi layered tablets [J].
Abdul, S ;
Poddar, SS .
JOURNAL OF CONTROLLED RELEASE, 2004, 97 (03) :393-405
[2]   A Quantitative Correlation of the Effect of Density Distributions in Roller-Compacted Ribbons on the Mechanical Properties of Tablets Using Ultrasonics and X-ray Tomography [J].
Akseli, Ilgaz ;
Iyer, Srinivas ;
Lee, Hwahsiung P. ;
Cuitino, Alberto M. .
AAPS PHARMSCITECH, 2011, 12 (03) :834-853
[3]   Mechanical Property Characterization of Bilayered Tablets using Nondestructive Air-Coupled Acoustics [J].
Akseli, Ilgaz ;
Dey, Dipankar ;
Cetinkaya, Cetin .
AAPS PHARMSCITECH, 2010, 11 (01) :90-102
[4]  
AULTON ME, 1981, PHARM ACTA HELV, V56, P133
[5]  
CHARMAN SA, 2002, MODIFIED RELEASE DRU, P1
[6]   Formulation and characterization of new layered diffusional matrices for zero-order sustained release [J].
Chidambaram, N ;
Porter, W ;
Flood, K ;
Qiu, YH .
JOURNAL OF CONTROLLED RELEASE, 1998, 52 (1-2) :149-158
[7]   MULTILAYERED HYDROPHILIC MATRICES AS CONSTANT RELEASE DEVICES (GEOMATRIX(TM) SYSTEMS) [J].
CONTE, U ;
MAGGI, L ;
COLOMBO, P ;
LAMANNA, A .
JOURNAL OF CONTROLLED RELEASE, 1993, 26 (01) :39-47
[8]   PLASTIC-FLOW DURING COMPRESSION OF DIRECTLY COMPRESSIBLE FILLERS AND ITS EFFECT ON TABLET STRENGTH [J].
DAVID, ST ;
AUGSBURGER, LL .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1977, 66 (02) :155-159
[9]   Topographic characterization of cellulose bilayered tablets interfaces [J].
Inman, S. J. ;
Briscoe, B. J. ;
Pitt, K. G. .
CHEMICAL ENGINEERING RESEARCH & DESIGN, 2007, 85 (A7) :1005-1012
[10]   COMPUTERIZED TOMOGRAPHY WITH X-RAY, EMISSION, AND ULTRASOUND SOURCES [J].
KAK, AC .
PROCEEDINGS OF THE IEEE, 1979, 67 (09) :1245-1272