W4367 BLISTER PACK PUSH-THROUGH FORCE AND … · BLISTER PACK PUSH-THROUGH FORCE AND ODT TABLET...
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BLISTER PACK PUSH-THROUGH FORCE AND ODT TABLET STRENGTH F. Cheng, M. Markham Aptalis Pharmatech, Inc., 845 Center Drive, Vandalia, Ohio 45377 Purpose An important criterion in choosing a blister pack for a pharmaceutical tablet is to ensure the tablet will not break when it is pushed through the package. This is especially important for weaker tablets such as orally disintegrating tablets (ODT). This investigation was carried out for the following purposes: (1) Evaluate the push-through force required to push tablets through blister packs. (2) Better understand how different blisters packs can impact the ability to push-through ODT products without causing tablet breakage. (3) Establish a strategy to design stronger ODT tablet to withstand the pushing through force by various dispensing skills from different users. Methods A Texture Analyzer, Model XT Plus, was used to measure the puncture force for aluminum foil blister pack backing; the blister pack push-through force; and the tablet crush-force. Cylindrical probes were used to measure the aluminum foil push-through forces and tablet diametrial strength. A three-point bending force probe was constructed with thin metal rods to test the bending force required to break a tablet in the unsupported midpoint. A conventional tablet hardness tester was also used for data comparison. Results Using the texture analyzer, aluminum foils of different thickness were tested for their push-through forces. Many commercially available blister packs were examined for their push-through forces, either with blister cover or having cover removed. It was found that the push-through forces correlated well to both the tablet sizes and aluminum foil thickness. Through the three-point bending forces studies, the relationship between the tablet dimensions and their ability to withstand the push-through force was established. Conclusion Some conclusions were obtained from this study: (1) For a tablet to be safely pushed through a blister pack, the backing material (e.g. aluminum lidding foils) must be thin and easy to be punctured. (2) Tablets with smaller diameters tend to be easier to push-through the blister pack. (3) Through the three-point bending force experiments, the results indicated that a tablet can have greater strength with smaller diameter and greater thickness. ■ ■ To evaluate the push-through force required to push tablets through blister packs, especially the ODT tablets of Aptalis Pharmaceutical Technologies. ■ ■ To study the ODT tablets strength and to design a better patient-centric tablet to withstand the pushing through force generated by different users. ■ ■ A Texture Analyzer was used to measure: (1) the puncture force for aluminum foil blister pack backing; (2) the blister pack push-through force; and (3) the tablet crush-force. ■ ■ A three-point bending force probe was constructed with thin metal rods to test the force required to break a tablet in the unsupported midpoint. ■ ■ A Dr. Schleuniger Tablet Hardness Tester was used to test the diametral tablet hardness. Figure 1 shows the experimental setup for the determination of aluminum foil strength (kg) against foil thickness (µm) by using a Texture Analyzer with a flat probe. 10 15 20 25 30 35 40 45 50 Hardness (N) TA Force (N) Tablet Strength Comparison 15 20 25 30 35 40 45 50 y = 0.9005x + 4.0453 R 2 = 0.9128 10 Tablet Thickness, H Radial Diameter, D Fx, Radial Breaking Force Tensile Strength F x F y σ x σ y Distance between supports, L 1. Amin, M.C.I. and Fell, J.T., Tensile Strength and Bonding in Compacts: A Comparison of Diametrial Compression and Three-Point Bending for Plastically Deforming Materials, Drug Develop. And Ind. Pharm., 2002, 28(7), 809-813. 2. Moser, J. D.; Ikeda, C. B.; Yao, D.; Chow, J.; and Chen, T.; Blister Push Through Force and Tablet Three Point Bend Strength as Means of Predicting Deblistering Performance, AIChE Annual Meeting, 2005. 3. Davies, P.N.; Worthington, H. E. C.; Podczeck, F; and Newton, J. M., The Determination of the Mechanical Strength of Tablets of Different Shapes, Eur. J. Pharm. Biopharm. 2007, 67, 268-276. ■ ■ For a tablet to be safely pushed through a blister pack, the backing material (e.g. aluminum foils) must be thin. ■ ■ Tablets with smaller diameters are easier to be pushed through the blister pack. ■ ■ The diametral crushing forces obtained by either a Texture Analyzer (TA) and a standard tablet hardness tester correlated well and either method can be used to measure the tablets strength. ■ ■ Through the three-point bending experiments, the results indicated that tablet thickness is a crucial factor to consider. ■ ■ It is therefore important in designing a fragile tablet, such as an ODT tablet, with a combination of the smallest tablet diameter and the thickest tablet height as possible to enhance the tablet strength. Abstract Conclusions References Objective Method Results Table 3. Tablet Hardness Data Comparison by Two Instruments Tablet # 1 2 3 4 5 TA Average (Newton) 37.0 18.8 47.8 26.9 31.6 Hardness Tester Average (Newton) 40.7 20.0 46.0 31.0 28.5 Table 4. Tensile Strength Comparison of Some ODT Tablets Tablet # 1 2 3 4 5 Tablet Diameter (D, in mm) 17.3 13.3 9.60 133 11.2 Tablet Thickness (H, in mm) 6.25 5.30 3.80 4.95 5.50 Average Diametral Strength, F x (kg) 3.795 1.882 4.869 2.745 3.176 Diametral Tensile Strength σ x =2F/πDH (kg/mm*mm) 0.0223 0.0171 0.0850 0.0266 0.0328 Average Three-Point Bending Force, F y (kg) 3.073 1.444 1.796 2.444 2.492 3-Point Tensile Strength σ y =3FL/2DH 2 (kg/mm*mm) 0.0443 0.0378 0.126 0.0734 0.0717 Table 2. Blister Pack Push-Through Force (kg) with and without Blister Cover Blister Pack # 1 2 3 4 5 API Content ACT 101 500 mg ACT 101 250 mg ACT 110 100 mg ACT 102 25 mg ACT 120 150 mg Blister Cavity Diameter (mm) 18.7 14.5 11.6 14.5 14.5 Blister Cavity Height (mm) 6.50 6.50 6.50 6.50 6.50 Tablet Diameter (mm) 17.0 13.0 9.50 13.0 11.0 Average Push-thru Force with Plastic cover (kg) 8.03 6.74 6.50 7.08 6.65 Average Push-thru Force with no Plastic cover (kg) 5.42 4.53 2.68 4.11 4.25 Difference in Force* (kg) 2.61 2.21 3.82 2.97 2.40 Table 1. Aluminum Foil Puncture Force (kg) vs. Foil Thickness (µm) W4367 Figure 1. Aluminum Foil Puncture Through Force Test Figure 3. Experiment Setup for Blister Pack Push-Through Force Study Figure 5. Comparison of Tablet Hardness Data Figure 6. Radial Breaking Force Figure 7. Tablet Three-Point Bending Force Foil Thickness (µm) 12.7 15.2 15.2 16.3 20.0 22.9 23.6 30.0 30.0 38.1 Force (kg, N= 3) 2.64 3.06 3.03 2.57 3.92 3.97 4.19 5.18 6.57 7.34 0 5 10 15 20 25 30 35 40 Force (kg) Foil Thickness (μm) Force (Kg, N=3) 1 2 3 4 5 6 7 8 y = 0.1936x - 0.0893 R 2 = 0.93195 0 Average Force (kg) Tablet Diameter (mm) Tablet Push-Through Force (Kg) 8 9 10 11 12 13 14 15 16 17 18 1 2 3 4 5 6 7 8 9 y = 0.2066x - 4.3761 R 2 = 0.90048 y = 0.3175x - 0.1656 R 2 = 0.8182 0 Average Pack Push-Through Force (kg) with Blister Cover Average Pack Push-Through Force (kg) without Blister Cover 0 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09 σy σx Correlations 0.02 0.04 0.06 0.08 0.1 0.12 0.14 y = 1.2049x + 0.0263 R 2 = 0.91127 0 Figure 2. Plot of the Puncture Force vs. Aluminum Foil Thickness Figure 4. Correlation between the Blister pack Push-Through Force and Tablet Diameter Figure 8. Comparison of Tensile Strength by Diametral and Bending Forces The aluminum lid foils on the blister packs were tested by measuring the tablet push-through forces with and without plastic blister cover. Figure 3 shows the experimental setup for measuring the blister pack push-through force. Table 2 displays the results of average blister pack push-through force of several ODT tablets, either in their original blister plastic or with the plastic cover cut off. The purpose of this study is to determine the effect of plastic cover to the push-through forces and to determine the relationship between push- through forces and tablet sizes. The results are plotted in Figure 4 and demonstrate that in both cases the push-through forces are proportional to the tablet diameters. *Difference due to the resistence from the plastic cover of blister pack The radial (diametral) strength of some ODT tablets was measured by both the Texture Analyzer and a Tablet Hardness Tester. Table 3 and Figure 5 compare the results obtained between the two instruments and indicate the results correlated well. Assuming a pharmaceutical tablet is made of isotropic material, the tablet’s radial tensile strength (σ x ) is directly related to its radial breaking force by equation (1): F x = σ x * (πDH)/2= σ x /2 * diametral surface area Eq. (1) Similarly, a tablet’s vertical tensile strength σy can be determined by its three point bending force F y as illustrated in Figure 7 and Eq. (2). F y = 2 σ y DH 2 /3L Eq. (2) The radial and three point bending forces of five ODT tablets were measured and their tensile strengths calculated. The results are shown in Table 4 and the tensile strengths are compared in Figure 8. There exists a correlation between the two tensile strengths of these tablets, with a correlation coefficient of 0.91. Rearrange Eq. 2: F y = 2 σ y DH 2 /3L= (4/3π) /L * {σ y *(πDH)}* H Since σ y ➞ σ x F y ➞ F x * H Therefore, a tablet made of isotropic material, the 3-point bending force is proportional to the Tablet Breaking Force multiply by the tablet thickness. Table 1 and Figure 2 display the results of this study. The results indicate a linear relationship between the puncture force and thickness. In a blister pack having aluminum backing thicker than 13 µm the tablet needs to withstand about 3 kg crushing force to be pushed through the pack. © 2014 Aptalis Pharmatech, Inc.
Transcript of W4367 BLISTER PACK PUSH-THROUGH FORCE AND … · BLISTER PACK PUSH-THROUGH FORCE AND ODT TABLET...
BLISTER PACK PUSH-THROUGH FORCE AND ODT TABLET STRENGTHF. Cheng, M. Markham
Aptalis Pharmatech, Inc., 845 Center Drive, Vandalia, Ohio 45377
PurposeAn important criterion in choosing a blister pack for a pharmaceutical tablet is to ensure the tablet will not break when it is pushed through the package. This is especially important for weaker tablets such as orally disintegrating tablets (ODT). This investigation was carried out for the following purposes: (1) Evaluate the push-through force required to push tablets through blister packs. (2) Better understand how different blisters packs can impact the ability to push-through ODT products without causing tablet breakage. (3) Establish a strategy to design stronger ODT tablet to withstand the pushing through force by various dispensing skills from different users.
MethodsA Texture Analyzer, Model XT Plus, was used to measure the puncture force for aluminum foil blister pack backing; the blister pack push-through force; and the tablet crush-force. Cylindrical probes were used to measure the aluminum foil push-through forces and tablet diametrial strength. A three-point bending force probe was constructed with thin metal rods to test the bending force required to break a tablet in the unsupported midpoint. A conventional tablet hardness tester was also used for data comparison.
ResultsUsing the texture analyzer, aluminum foils of different thickness were tested for their push-through forces. Many commercially available blister packs were examined for their push-through forces, either with blister cover or having cover removed. It was found that the push-through forces correlated well to both the tablet sizes and aluminum foil thickness. Through the three-point bending forces studies, the relationship between the tablet dimensions and their ability to withstand the push-through force was established.
ConclusionSome conclusions were obtained from this study: (1) For a tablet to be safely pushed through a blister pack, the backing material (e.g. aluminum lidding foils) must be thin and easy to be punctured. (2) Tablets with smaller diameters tend to be easier to push-through the blister pack. (3) Through the three-point bending force experiments, the results indicated that a tablet can have greater strength with smaller diameter and greater thickness.
■■ To evaluate the push-through force required to push tablets through blister packs, especially the ODT tablets of Aptalis Pharmaceutical Technologies.
■■ To study the ODT tablets strength and to design a better patient-centric tablet to withstand the pushing through force generated by different users.
■■ A Texture Analyzer was used to measure: (1) the puncture force for aluminum foil blister pack backing; (2) the blister pack push-through force; and (3) the tablet crush-force.
■■ A three-point bending force probe was constructed with thin metal rods to test the force required to break a tablet in the unsupported midpoint.
■■ A Dr. Schleuniger Tablet Hardness Tester was used to test the diametral tablet hardness.
Figure 1 shows the experimental setup for the determination of aluminum foil strength (kg) against foil thickness (µm) by using a Texture Analyzer with a flat probe.
10 15 20 25 30 35 40 45 50
Har
dn
ess
(N)
TA Force (N)
Tablet Strength Comparison
15
20
25
30
35
40
45
50
y = 0.9005x + 4.0453R2 = 0.9128
10
Tablet Thickness, H
Radial Diameter, D
Fx, Radial Breaking Force
Tensile Strength
Fx
Fy
σx
σy
Distance betweensupports, L
1. Amin, M.C.I. and Fell, J.T., Tensile Strength and Bonding in Compacts: A Comparison of Diametrial Compression and Three-Point Bending for Plastically Deforming Materials, Drug Develop. And Ind. Pharm., 2002, 28(7), 809-813.
2. Moser, J. D.; Ikeda, C. B.; Yao, D.; Chow, J.; and Chen, T.; Blister Push Through Force and Tablet Three Point Bend Strength as Means of Predicting Deblistering Performance, AIChE Annual Meeting, 2005.
3. Davies, P.N.; Worthington, H. E. C.; Podczeck, F; and Newton, J. M., The Determination of the Mechanical Strength of Tablets of Different Shapes, Eur. J. Pharm. Biopharm. 2007, 67, 268-276.
■■ For a tablet to be safely pushed through a blister pack, the backing material (e.g. aluminum foils) must be thin.
■■ Tablets with smaller diameters are easier to be pushed through the blister pack.
■■ The diametral crushing forces obtained by either a Texture Analyzer (TA) and a standard tablet hardness tester correlated well and either method can be used to measure the tablets strength.
■■ Through the three-point bending experiments, the results indicated that tablet thickness is a crucial factor to consider.
■■ It is therefore important in designing a fragile tablet, such as an ODT tablet, with a combination of the smallest tablet diameter and the thickest tablet height as possible to enhance the tablet strength.
Abstract
Conclusions
References
Objective
Method
Results
Table 3. Tablet Hardness Data Comparison by Two Instruments
Tablet # 1 2 3 4 5
TA Average (Newton) 37.0 18.8 47.8 26.9 31.6
Hardness Tester Average (Newton) 40.7 20.0 46.0 31.0 28.5
Table 4. Tensile Strength Comparison of Some ODT Tablets
Tablet # 1 2 3 4 5
Tablet Diameter (D, in mm) 17.3 13.3 9.60 133 11.2
Tablet Thickness (H, in mm) 6.25 5.30 3.80 4.95 5.50
Average Diametral Strength, Fx (kg) 3.795 1.882 4.869 2.745 3.176
Diametral Tensile Strength σx=2F/πDH (kg/mm*mm)
0.0223 0.0171 0.0850 0.0266 0.0328
Average Three-Point Bending Force, Fy (kg) 3.073 1.444 1.796 2.444 2.492
3-Point Tensile Strength σy=3FL/2DH2 (kg/mm*mm)
0.0443 0.0378 0.126 0.0734 0.0717
Table 2. Blister Pack Push-Through Force (kg) with and without Blister Cover
Blister Pack # 1 2 3 4 5
API ContentACT 101 500 mg
ACT 101 250 mg
ACT 110 100 mg
ACT 102 25 mg
ACT 120 150 mg
Blister Cavity Diameter (mm) 18.7 14.5 11.6 14.5 14.5
Blister Cavity Height (mm) 6.50 6.50 6.50 6.50 6.50
Tablet Diameter (mm) 17.0 13.0 9.50 13.0 11.0
Average Push-thru Force with Plastic cover (kg)
8.03 6.74 6.50 7.08 6.65
Average Push-thru Force with no Plastic cover (kg)
5.42 4.53 2.68 4.11 4.25
Difference in Force* (kg) 2.61 2.21 3.82 2.97 2.40
Table 1. Aluminum Foil Puncture Force (kg) vs. Foil Thickness (µm)
W4367
Figure 1. Aluminum Foil Puncture Through Force Test
Figure 3. Experiment Setup for Blister Pack Push-Through Force Study
Figure 5. Comparison of Tablet Hardness Data
Figure 6. Radial Breaking Force
Figure 7. Tablet Three-Point Bending Force
Foil Thickness (µm) 12.7 15.2 15.2 16.3 20.0 22.9 23.6 30.0 30.0 38.1
Force (kg, N= 3) 2.64 3.06 3.03 2.57 3.92 3.97 4.19 5.18 6.57 7.34
0 5 10 15 20 25 30 35 40
Forc
e (k
g)
Foil Thickness (µm)
Force (Kg, N=3)
1
2
3
4
5
6
7
8
y = 0.1936x - 0.0893R2 = 0.93195
0
Ave
rag
e Fo
rce
(kg
)
Tablet Diameter (mm)
Tablet Push-Through Force (Kg)
8 9 10 11 12 13 14 15 16 17 18
1
2
3
4
5
6
7
8
9 y = 0.2066x - 4.3761
R2 = 0.90048
y = 0.3175x - 0.1656R2 = 0.8182
0
Average Pack Push-Through Force (kg) with Blister Cover
Average Pack Push-Through Force (kg) without Blister Cover
0 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09
σy
σx
Correlations
0.02
0.04
0.06
0.08
0.1
0.12
0.14
y = 1.2049x + 0.0263R2 = 0.91127
0
Figure 2. Plot of the Puncture Force vs. Aluminum Foil Thickness
Figure 4. Correlation between the Blister pack Push-Through Force and Tablet Diameter
Figure 8. Comparison of Tensile Strength by Diametral and Bending Forces
The aluminum lid foils on the blister packs were tested by measuring the tablet push-through forces with and without plastic blister cover. Figure 3 shows the experimental setup for measuring the blister pack push-through force.
Table 2 displays the results of average blister pack push-through force of several ODT tablets, either in their original blister plastic or with the plastic cover cut off. The purpose of this study is to determine the effect of plastic cover to the push-through forces and to determine the relationship between push-through forces and tablet sizes.
The results are plotted in Figure 4 and demonstrate that in both cases the push-through forces are proportional to the tablet diameters.
*Difference due to the resistence from the plastic cover of blister pack
The radial (diametral) strength of some ODT tablets was measured by both the Texture Analyzer and a Tablet Hardness Tester. Table 3 and Figure 5 compare the results obtained between the two instruments and indicate the results correlated well.
Assuming a pharmaceutical tablet is made of isotropic material, the tablet’s radial tensile strength (σx) is directly related to its radial breaking force by equation (1):
Fx= σx * (πDH)/2= σx/2 * diametral surface area Eq. (1)
Similarly, a tablet’s vertical tensile strength σy can be determined by its three point bending force Fy as illustrated in Figure 7 and Eq. (2).
Fy= 2 σyDH2/3L Eq. (2)
The radial and three point bending forces of five ODT tablets were measured and their tensile strengths calculated. The results are shown in Table 4 and the tensile strengths are compared in Figure 8. There exists a correlation between the two tensile strengths of these tablets, with a correlation coefficient of 0.91.
Rearrange Eq. 2:
Fy= 2 σyDH2/3L= (4/3π) /L * {σy *(πDH)}* H
Since σy ➞ σx
Fy➞ Fx * H
Therefore, a tablet made of isotropic material, the 3-point bending force is proportional to the Tablet Breaking Force multiply by the tablet thickness.
Table 1 and Figure 2 display the results of this study. The results indicate a linear relationship between the puncture force and thickness. In a blister pack having aluminum backing thicker than 13 µm the tablet needs to withstand about 3 kg crushing force to be pushed through the pack.
© 2014 Aptalis Pharmatech, Inc.
