Influence of physical factors on quality attributes of scored tablets

Christopher Gaudnick Larin, Louis-Martin Kojoian, Dorothy Paslawski, Stephan Sebastiampillai, Nathaniel Wong, Miloud Rahmouni, and Mohammed Nabil Khalid
Department of Biopharmaceutical Production Technology, John Abbott College, 21 275 Lakeshore Road, H9X 3L9, Sainte-Anne-de-Bellevue, QC, Canada

INTRODUCTION ABSTRACT RESULTS AND DISCUSSION

Scored tablets are designed with the purpose to adjust the administration dose of Purpose: Scored tablets are designed with the purpose to adjust the administration dose, to Tablet with deep line score are easy to break and show a good
the active ingredient, to facilitate swallowing, and to reduce the medication cost. facilitate swallowing, and to reduce the medication cost. It has been reported that splitting breaking accuracy compared to simple score tablet (Figure 2A and
The presence of a score mark on one or both faces of the tablet implies the scored tablets will generate significant high weight variation of split fragments. Caution 2B) .
dosage form may be subdivided in two half or more fragments, giving more dose has to be taken when attempting to split CR tablets, or tablets that contains narrow
flexibility to the patient. therapeutic index drugs. The purpose of this work is to investigate the effect of some
However, many patients, especially elderly patients, have difficulties to break the physical and technological parameters that might affect the accuracy, breaking ease, and
scored tablet in two parts. Moreover, some studies have reported that when other quality attribute of scored tablet. Figure 2A
scored tablet are subdivided in multiple parts, either by hand or by tablet splitter, Method: Tablets containing 1:1 blend of MCC and lactose, as well as MCC Emcompress,
the split tablet fragments present a significant high weight variability (1). Caution were prepared by direct compression using a rotary tablet press. Scored tablets of different
has to be taken when attempting to split controlled release tablets, or tablets that shapes; round, oval, square, were compressed at low, medium and high compression force.
contains narrow therapeutic index drugs. The scored tablets were then slit in different parts by hand and using a tablet splitter. The
whole tablets as well as the split tablet fragments were then evaluated for their friability,
hardness, thickness, weight variation, breaking force, and disintegration test.
OBJECTIVE Results: Split tablet either by hand or splitter tablet generates higher weight variability as
compared to the whole tablets. Split tablet by hand has shown a lower accuracy compared
The objective of this work is to investigate the effect of some physical (i.e. to tablet splitter. Tablets with deep line score are easy to break and show a good breaking Figure 2B
hardness and thickness) and technological parameters (tablet shape, deepness and accuracy compared to unscored tablets. Tablet hardness and table shape significantly affect
curvature of the score line) that might affect the accuracy, breaking ease, and the the breaking accuracy, while tablet size has almost no affect.
quality attribute of splitting scored tablet Conclusion: Formulation composition, process manufacturing and other physical
characteristics have greater influence on the accuracy of split tablet.
Manufacturing process of scored tablet by wet granulation method
MATERIALS AND METHODS has no effect on breaking accuracy, compared to direct compression,
RESULTS AND DISCUSSION but significantly affect the breaking force of the tablet (as shown in
Preparation of placebo tablets: Figure 3).
 Placebo Tablets containing MCC and compressible sugar were prepared by Tablet characterization:
direct compression and wet granulation process using an instrumented  Mechanical tablet strength: Tablet hardness was measured using a hardness tester
tablet press (RoTab, Germany) and different scored punches. The complete machine (Vector, USA), while friability was measured using a friabilator apparatus
formulation composition is given in Table 1. (Sotax, USA).
 Weight variation: 10 tablets were split in halves using a tablet splitter, and other 10
Ingredients Role Tablet composition
tablets were split in halves by hand. The whole tablets as well as the split halves were
mg %
weighed using an analytical balance (Mettler Toledo, USA). The tablet fragment
MCC PH101 Binder 2000.0 40.00 weights were compared to the ideal half-tablet weight to assess the splitting accuracy.
Compressible sugar (DiPac®) Diluent 2750.0 55.00
Acceptance criteria of RSD less than 6% was adopted as it was recommended by USP
Na Starch Glycolate (Explotab®) Disintegrant 175.0 3.50
chapter <905> for the uniformity of dosage units. Table 3: Effect of tablet manufacturing process on breaking force
Colloidal silicon dioxide Glidant 25.0 0.50  Breaking ease: the applied force to break the tablet in 2 halves was evaluated using a
Magnesium stearate Lubricant 50.0 1.00 texture analyser TA-XT2i Plus (Texture Technologies corp., USA) equipped with a ¼” Finally, tablet hardness and table shape significantly affect the
Total 5000.0 100.00 spherical ball probe (TA-18) connected to a 5kg load cell. breaking accuracy, while tablet size has almost no affect (data not
Results shown).
Table 1: Formulation of placebo tablet
 Splitting a scored tablet in 2 halves either by hand or tablet cutter generates higher CONCLUSION
weight variability as compared to the whole tablets (See Figure 1).
 Wet granulation was carried out in a planetary mixer (Hobart, Canada) The results of the present study shows that the presence of scored line
using a placebo formulation consisting of a mixture of MCC and in a tablet should not imply that tablet will break easy and accurately.
compressible sugar. Aqueous solution of Povidon K30 (4% w/w) was Many parameters such as deep scoring, tablet hardness,
gradually added to the placebo mixture until a wet mass was formed. The manufacturing process, and splitting method could significantly affect
wet mass was screened through a 16-mesh screen then dried at 40oC the breaking accuracy of the tablet. This could have serious clinical
overnight in an oven. The dry granules were first blended with silicon consequences, especially for medications with a narrow therapeutic
dioxide, then with magnesium stearate in a 16-quarts V-blender, and then index.
compressed on a rotary tablet press (RoTab, Germany).
References:
1. Van Santen E., Barends DM., and Frijlink HW. (2002) Breaking of scored
tablets: a review. Eur. J. Pharm. Biopharm. Vol. 53, No. 2, pp. 139 -145.
2. Habib W., Alanizi A., Abdelhamid M., Alanizi FK. (2014) Accuracy of tablet
Figure 1: Formulation of placebo tablet
splitting comparison study between hand splitting and tablet cutter. Saudi
Pharm. J. vol. 22, pp. 454 - 459