Quality Attribute 
Considerations for 
Chewable Tablets
Guidance for Industry 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
August 2018 
Pharmaceutical Quality/CMC 
8938436 FNL   
Quality Attribute 
Considerations for 
Chewable Tablets
 
Guidance for Industry 
 
Additional copies are available from: 
Office of Communications, Division of Drug Information  
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD 20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 
Email: druginfo@fda.hhs.gov 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
August 2018 
Pharmaceutical Quality/CMC 
 
  Contains Nonbinding Recommendations 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  DISCUSSION .................................................................................................................... 2 
A.  Hardness ......................................................................................................................................... 3 
B.    Disintegration ................................................................................................................................. 3 
C.    Dissolution ...................................................................................................................................... 4 
D.   Performance in Simulated Physiological Media ......................................................................... 4 
E.  Use of In Vitro Bioequivalence Data and Postapproval Considerations .................................. 5 
IV.  RECOMMENDATIONS .................................................................................................. 5 
A.  Patient Acceptability and In vivo Performance .......................................................................... 5 
B.  Buccal Absorption .......................................................................................................................... 6 
C.  Critical Quality Attributes ............................................................................................................ 6 
D.  Nomenclature and Labeling .......................................................................................................... 8 
APPENDIX I:  CHEWING DIFFICULTY INDEX FOR FLAT-FACED ROUND 
TABLETS ........................................................................................................................ 10 
FIGURES ..................................................................................................................................... 12 
APPENDIX II:  SIMULATED SALIVARY FLUID COMPOSITION ................................ 13 
  Contains Nonbinding Recommendations 
Quality Attribute Considerations for Chewable Tablets 
Guidance for Industry1 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
this topic.  It does not establish any rights for any person and is not binding on FDA or the public.  You 
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.  
To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the 
title page.   
 
 
 
 
I.  INTRODUCTION  
 
This guidance provides manufacturers of chewable tablets2 for human use with the Center for 
Drug Evaluation and Researchs (CDER) current thinking on the critical quality attributes that 
should be assessed during the development of these drug products.3 This guidance also provides 
recommendations for sponsors/applicants regarding the submission of developmental, 
manufacturing, and labeling information for chewable tablets in applications. The 
recommendations in this guidance apply to new drug applications (NDAs), abbreviated new drug 
applications (ANDAs),4 and certain chemistry, manufacturing, and controls (CMC) supplements 
to these applications.5 Some of the recommendations about the submission of developmental 
information may also apply to investigational new drug applications (INDs). The 
recommendations about assessing critical quality attributes apply to all immediate release (IR) 
chewable tablets for human use, including non-application products. 
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
as recommendations, unless specific regulatory or statutory requirements are cited. The use of 
the word should in Agency guidances means that something is suggested or recommended, but 
not required.  
 
 
                                                 
1 This guidance has been prepared by the Office of Pharmaceutical Quality in the Center for Drug Evaluation and 
Research at the Food and Drug Administration. 
2 This guidance applies only to chewable tablets and not other chewable dosage forms.  
3 Products covered by these recommendations include over-the-counter (OTC) monograph products as well as 
prescription and OTC drug products that must be approved by CDER before they can be distributed. 
4 With respect to the applicability of this guidance to ANDAs  including recommendations for underlying design 
and other development determinations  is that Section 505(j)(2)(A) of the Federal Food, Drug, and Cosmetic Act 
requires a generic product to be the same as its reference listed drug in a number of relevant ways.  These 
requirements further may inform acceptable quality attributes for a proposed generic product in addition to the 
recommendations in this guidance.   
5 This guidance should be considered for CMC supplements submitted for modifications that affect the formulation 
or other critical quality attributes of a chewable tablet. 
  1  Contains Nonbinding Recommendations 
II.  BACKGROUND 
 
Chewable tablets are an oral dosage form intended to be chewed and then swallowed by the 
patient rather than swallowed whole. They should be designed to be palatable and be easily 
chewed and swallowed. Chewable tablets should be safe and easy to use in a diverse patient 
population of pediatric, adult, or elderly patients who are unable or reluctant to swallow intact 
tablets due to the size of the tablet or difficulty with swallowing. The availability of safe, easy-
to-use dosage forms is important in clinical practice. Chewable tablets are available for many 
over-the-counter (OTC) and prescription drug products. 
 
The United States Pharmacopeia (USP) recognizes and differentiates between two types of 
chewable tablets: (1) those that may be chewed for ease of administration, and (2) those that 
must be chewed or crushed before swallowing to avoid choking and/or to ensure the release of 
the active ingredient.6  The concepts in this guidance are applicable to both types of chewable 
tablets.  
 
Adverse events reported for chewable tablets include gastrointestinal (GI) obstruction resulting 
from patients swallowing whole or incompletely chewed tablets, and tooth damage or denture 
breakage resulting from excessive tablet hardness, and other esophageal irritation.7 In light of 
these reported adverse events, the Agency reviewed approved drug product applications for 
chewable tablets and found that in certain cases critical quality attributes such as hardness, 
disintegration, and dissolution were not consistently evaluated. This was evidenced by instances 
of incomplete monitoring of all relevant critical quality attributes or the use of widely ranging 
values that were not justified as acceptance criteria. In addition, a wide variation in analytical 
procedures has been reported.8,9,10   
 
This guidance describes the critical quality attributes that should be considered when developing 
chewable tablets and recommends selection of acceptance criteria that are appropriate and 
meaningful indicators of product performance throughout the shelf life of the product.  
 
 
III.  DISCUSSION     
 
A variety of physical characteristics should be considered in the manufacturing process for 
chewable tablets. An ideal chewable tablet should be: 
 
  Easy to chew 
                                                 
6 USP-NF <1151> Pharmaceutical Dosage Forms. 
7 For general information on collection of Adverse Event Reports by FDA, see 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/default.ht
m. 
8 USP-NF < 1217> Tablet Breaking Force. 
9 David ST and LL Augsburger, 1974, Flexure test for determination of tablet tensile strength, J Pharm Sci, 63:933-
936. 
10 Ambros MC, F Podczeck, H Podczeck H, JM Newton, 1998, The characterization of the mechanical strength of 
chewable tablets, Pharm Dev Tech, 3:509-515. 
 
  2  Contains Nonbinding Recommendations 
  Palatable (taste masked or of acceptable taste)  
  Of appropriate size and shape11  
  Able to disintegrate readily to facilitate dissolution  
 
Critical quality attributes for chewable tablets should include hardness, disintegration, and 
dissolution, as well as all factors that may influence drug bioavailability and bioequivalence. In 
addition, careful attention should be given to tablet size, thickness, and friability, as well as taste, 
which may impact the ability or willingness of a patient to chew the chewable tablet (i.e., a 
patient may swallow whole, rather than chew, a bad tasting tablet). No single quality 
characteristic is considered sufficient to control the performance of a chewable tablet. Instead, 
the goal should be to develop the proper combination of these attributes to ensure the 
performance of the chewable tablet for its intended use.  
 
A.  Hardness 
 
The hardness of chewable tablets should be such that they withstand the rigors of manufacturing, 
packaging, shipping, and distribution, as well as be easily chewed by the intended patient 
population. Hardness is generally measured as the force needed to break the tablet in a specific 
plane. Public standards exist to ensure consistent measurement of the tablet hardness (Tablet 
Breaking Force12). Tablet hardness may be measured and expressed in a variety of units.13 
Applications submitted to FDA should use the same unit of measure in reporting testing results 
and specifications.  
 
An index has been developed that factors tablet hardness with the load to break that tablet to 
create a numerical value that can be used to compare chewable tablets for their ease of being 
chewed.14 See Appendix I of this document for the description and rationale for this index 
(Chewing Difficulty Index). We encourage sponsors/applicants to accumulate and submit 
Chewing Difficulty Index data during product development.15 
 
B.    Disintegration 
 
The time required for a tablet to break up into small particles is its disintegration time. For 
chewable tablets, disintegration time should be short enough to prevent GI obstruction in the 
                                                 
11 For tablets that may be chewed or swallowed whole, the guidance for industry Size, Shape, and Other Physical 
Attributes of Generic Tablets and Capsules recommends that the largest dimension of a tablet intended to be 
swallowed whole should not exceed 22 mm. While this guidance was created for ANDA applicants, we believe that 
the size recommendations are reasonable for all marketed drug products. We update guidances periodically. To 
make sure you have the most recent version of a guidance, check the FDA Drugs guidance web page at 
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. 
12 See footnote 8.  
13 Units for hardness are expressed as: kilopond (kp), kilogram-force (kgf), Newton (N), and Strong-Cobb Units 
(scu). 1 kp = 1 kgf = 9.8 N = 1.4 scu.   
14 Gupta A, Chidambaram N, Khan MA. 2015. An index for evaluating difficulty of chewing the chewable tablets. 
Drug Dev Ind Pharm. 41:239-243.   
15 The Agency intends to evaluate submitted Chewing Difficulty Index data and update this guidance in the future as 
appropriate.  
 
  3  Contains Nonbinding Recommendations 
event a tablet is not completely chewed by the patient. Usually, the presence of the correct type 
and amount of a disintegrant facilitates rapid disintegration of the tablet. In vitro disintegration 
testing should be conducted using intact tablets in suitable medium using established 
disintegration equipment (such as USP Disintegration Apparatus) and methods.16  
 
C.    Dissolution 
 
Drug absorption from chewable tablets depends on the release of the drug substance(s) from the 
intact or the chewed tablets; therefore, in vitro dissolution testing of chewable tablets should 
follow the principles of dissolution testing of conventional IR tablets.17 That is, the active 
pharmaceutical ingredient(s) of the chewable tablets should adequately dissolve out of the tablet.  
 
For product characterization during development, in vitro dissolution testing should be 
conducted on intact tablets in at least four media, such as water, aqueous media at pH 1.2, 
buffered aqueous media at pH 4.5, and buffered aqueous media at pH 6.8, with established 
dissolution methods using equipment such as USP Apparatus 1 (basket), USP Apparatus 2 
(paddle), or USP Apparatus 3 (reciprocating cylinder).18  
 
D.   Performance in Simulated Physiological Media 
 
A sound understanding and assessment of the factors impacting the in vivo performance of drug 
products is needed during drug development. Utilizing in vitro methods that use simulated 
physiological media such as saliva and gastric fluids can provide an assessment of likely in vivo 
performance of oral dosage forms, particularly those made with poorly soluble drug 
substances.19,20,21,22  
 
In particular, chewable tablets should be evaluated using dissolution media such as simulated 
fasted and fed state gastric and intestinal fluids with enzymes (biorelevant dissolution media).  
Hardness testing after brief exposure (30 seconds) to a small quantity (for example, 1 mL) of 
human simulated saliva may provide data that could be used to support the hardness 
specification.23 In vitro testing in physiological media consistent with the targeted patient 
population characteristics may support further characterization of the drug product and its critical 
quality attributes. 
                                                 
16 USP-NF <701> Disintegration. 
17 See guidance for industry Dissolution Testing of Immediate Release Solid Oral Dosage Forms. When final, this 
guidance will represent the FDAs current thinking on this topic. 
18 USP-NF <711> Dissolution. 
19 Dressman JB, GL Amidon, C Reppas, VP Shah, 1998, Dissolution testing as a prognostic tool for oral drug 
absorption: immediate release dosage forms, Pharm Res, 15:11-22. 
20 Klein S, 2010, The Use of Biorelevant Dissolution Media to Forecast the in vivo Performance of a drug, AAPS J, 
12:3, 397-406.  
21 Markopoulos C, CJ Andreas, M Vertzoni, J Dressman, C Reppas, 2015, In-vitro simulation of luminal conditions 
for evaluation of performance of oral drug products: Choosing the appropriate test media, Europ J Pharm and 
Biopharm, 93:173-182. 
22 Marques MRC, R Loebenberg, and M Almukainz, 2011, Simulated Biological Fluids with Possible Application in 
Dissolution Testing, Dissolution Technologies, 15-28. 
23 See footnote 14. 
 
  4  Contains Nonbinding Recommendations 
 
E.  Use of In Vitro Bioequivalence Data and Postapproval Considerations 
 
The solubility and permeability characteristics of the drug substance may be used to determine 
where the drug fits within the Biopharmaceutics Classification System (BCS). Depending on the 
BCS classification of the drug substance, use of in vitro data to support bioequivalence (BE) may 
be considered for chewable tablets.24 Changes in the chemistry, manufacturing, and controls 
after approval of the chewable tablets should be made in conformance with the principles 
outlined in the Scale-up and Post-Approval Changes Immediate Release (SUPAC IR) guidance.25 
 
 
IV.  RECOMMENDATIONS 
 
The following general and specific recommendations should be considered during the 
development of a chewable tablet.   
 
A.  Patient Acceptability and In vivo Performance  
 
Potential product design and development considerations should include disintegrant(s) to 
facilitate release of the active ingredient, and sweeteners and flavoring agents for taste-
masking.26,27 The possibility of the interaction of excipients with each other and/or the drug 
substance(s), and their likely impact on the manufacturing process, should be evaluated.   
 
For an NDA, the following information should be collected during the conduct of clinical trials 
and reported : 
 
1.  Was the subjects sensory experience associated with chewing the tablet acceptable (e.g., 
taste, mouthfeel, and aftertaste)? 28,29 
 
2.  Did subjects have difficulty in thoroughly chewing the tablet (i.e., were the tablets 
inadvertently swallowed intact)? 
 
3.  If inadvertently swallowed intact, does the shape and size of the chewable tablet pose a 
choking or bowel obstruction risk?30  
 
4.  If water was used to aid swallowing, what was the volume? 
                                                 
24 See guidance for industry Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release 
Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System.  
25 See guidance for industry Immediate Release Solid Oral Dosage Forms: Scale-up and Postapproval Changes:  
Chemistry, Manufacturing, and Controls, In Vitro Dissolution Testing, and In Vivo Bioequivalence Documentation.  
26 The Agency recommends the use of sweeteners that do not contribute to dental decay. 
27 See guidance for industry Q8(R2) Pharmaceutical Development.  
28 See footnote 9. 
29 European Medicines Agency, 2006, Reflection Paper: Formulations of choice for the pediatric population. 
EMEA/CHMP/PEG/194810/2005. 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003782.pdf. 
30 See footnote 9. 
  5  Contains Nonbinding Recommendations 
 
For ANDA applications for which in vivo bioequivalence studies are conducted, general 
information such as the subjects sensory experience (acceptability of taste, mouthfeel, and 
aftertaste) and ease of swallowing  in the event that the tablet is not thoroughly chewed  
should be collected during the conduct of bioequivalence studies and reported in the subsequent 
ANDA.   
 
B.  Buccal Absorption 
 
The potential for buccal absorption of the drug substance should be evaluated and described in 
the NDA. The importance of any buccal absorption may depend on the solubility and 
permeability characteristics of the drug substance, its stability in saliva (over a pH range 6.0 to 
7.5), and whether it undergoes extensive first-pass metabolism.   
 
Stability in the buccal environment can usually be assessed in vitro. For example, studies at the 
applicable pH range over a short period of time (e.g., <5 min) showing minimal drug substance 
release or lack of degradation of the drug substance may be adequate to demonstrate short-term 
stability in the buccal environment.   
 
C.  Critical Quality Attributes 
 
Appropriate acceptance criteria for hardness, dissolution, and disintegration of the chewable 
tablet should be established early in development. FDA recommends that multiple attributes be 
studied to address the performance of the chewable tablet and incorporated in the product 
specification. Reliance on only one attribute should be avoided.  
 
For drug products that require filing of an application with the Agency, the development 
information should be provided in section 3.2.P.2 (Pharmaceutical Development) of a common 
technical document (CTD)-formatted submission. The information on tablet hardness, 
disintegration and dissolution should be provided in section 3.2.P.3.4 (Control of Critical Steps 
and Intermediates) or section 3.2.P.5.1 (Specifications) of a CTD-formatted application.31 
Sponsors/applicants are encouraged to calculate and submit the chewing difficulty index (see 
Appendix I) in section 3.2.P.2.  
 
The Agency recommends that applicants of currently approved chewable tablets and sponsors of 
nonapplication chewable tablets reevaluate the products critical quality attributes and ensure 
appropriate specifications are in place considering the recommendations above.32 If the Agency 
identifies that a marketed chewable tablet poses a particular risk to public health because it is 
difficult to chew (e.g., causes damage to teeth or dentures, or GI obstruction), the Agency will 
communicate with the sponsor/applicant or manufacturer and consider appropriate action to 
alleviate the risk to public health. 
                                                 
31 ICH Harmonised Tripartite Guideline, 2002, The Common Technical Document for the Registration of 
Pharmaceuticals for Human Use: Quality  M4Q(R1). 
32 Reevaluation of critical quality attributes can be accomplished through review of historical data from development 
and validation studies, adverse event reporting, customer complaint trends, or through collection of new data. 
 
  6  Contains Nonbinding Recommendations 
 
  Hardness  
 
  Based on the review of applications and literature sources, the Agency 
o
recommends that hardness for chewable tablets be kept low (e.g., <12 kp).33 
 
  A higher hardness value (e.g., >12 kp) may be considered if justified. An 
o
example of such justification could be demonstrating significant disintegration 
and/or reduction in hardness of such tablets following brief (approximately 30 
seconds) exposure to saliva before chewing. An in vivo study may be 
performed using human volunteers, or an in vitro study may be conducted in 
which the tablet is exposed to a small quantity (e.g., 1 mL) of simulated 
salivary fluid (see Appendix II) for 30 seconds.  
 
  In all other cases, the sponsor/applicant should provide justification for the 
o
proposed hardness, including studies demonstrating that the tablet can be 
readily chewed by the intended population without GI obstruction, damage to 
teeth or dentures, or other adverse events related to chewing these tablets.   
 
  In addition to evaluating the hardness of chewable tablets, the 
o
sponsor/applicant should consider evaluating the tablets for the chewing 
difficulty index (see Appendix I) both before and after exposure to human 
saliva.   
 
  Disintegration and Dissolution 
 
  Chewable tablets should typically meet the same disintegration and 
o
dissolution specifications as IR tablets. 
 
  In vitro dissolution testing should be conducted on intact chewable tablets 
o
since it is possible that some patients might swallow the tablets without 
chewing. Crushing of the chewable tablets prior to conducting in vitro 
dissolution testing generally is not recommended since there is currently no 
reported validated method for this process. Furthermore, this approach would 
be unlikely to result in experimental conditions simulating a range of chewing 
patterns that might be observed in different patient populations. However, 
additional dissolution assessments may be needed on a case-by-case basis 
based on product-specific information.   
 
  It is possible to use other methods, as long as the proposed methods are 
o
demonstrated to be equivalent or superior to the existing approaches.  
 
                                                 
33 In general, adverse events were not associated with the hardness value of < 12 kp in approved products. The 
Agency recognizes that tablet size and shape are important in determining acceptable tablet hardness. For example, 
for a very small tablet, a hardness value of 12 kp may be quite high.   
  7  Contains Nonbinding Recommendations 
  Other Critical Quality Attributes  
 
  If other critical quality attributes are applicable to a particular chewable tablet, 
o
they should be evaluated using Agency-recommended methods or using 
methods that are demonstrated to be equivalent or superior to the existing 
approaches. For example, if the chewable tablet consists of functionally- 
coated particles, it is important to ensure the functional coating continues to 
perform after the tablet is chewed. 
 
D.  Nomenclature and Labeling   
 
As previously stated, the USP recognizes and differentiates between two types of chewable 
tablets: (1) those that may be chewed for ease of administration, and (2) those that must be 
chewed and/or crushed before swallowing to avoid choking and to ensure the release of the 
active ingredient.34 These two types of chewable tablets are differentiated by the way they 
are named and labeled.35,36 
 
  The text [DRUG] Tablets will be used for tablets that MAY be chewed or 
swallowed in their entirety.  The labels and labeling for these products will also 
include a labeling statement indicating that the tablets MAY be chewed. 
 
  The text  [DRUG] Chewable Tablets will be used for tablets that MUST be chewed 
and for which there is no alternative route of administration.  The labels and labeling 
for these products will also include a labeling statement indicating that the tablets 
MUST be chewed. 
  
To help prevent patients from swallowing intact [DRUG] Chewable Tablets, it is strongly 
recommended that the principal display panel of the container label and the carton labeling 
(if applicable) prominently state the following:  
 
Chew or crush tablets completely before swallowing. 
 
If space permits, it is recommended that the following statement be displayed on the 
principle display panel with lesser prominence to reinforce the importance of chewing the 
tablets: 
 
Do not swallow tablets whole. 
 
Additionally, language similar to the previously mentioned statements should appear in the 
DOSAGE AND ADMINISTRATION and PATIENT COUNSELING INFORMATION  
sections of the prescribing information as well as other sections when appropriate, and any 
                                                 
34 See footnote 6. 
35 See guidance for industry Product Title and Initial U.S. Approval in the Highlights of Prescribing Information for 
Human Prescription Drug and Biological Products-Content and Format. 
36 The format of the dosage form may differ in the prescribing information, FDA-approved patient labeling, and 
carton/container labeling. 
  8  Contains Nonbinding Recommendations 
accompanying patient labeling (e.g., Medication Guide, Patient Package Insert, Instructions 
for Use) if applicable. 
  9  Contains Nonbinding Recommendations 
APPENDIX I:  CHEWING DIFFICULTY INDEX FOR FLAT-FACED ROUND 
TABLETS 
 
One of the critical quality attributes for tablets, tablet hardness,37 also referred to as breaking 
force or crushing force, is the force required to cause the tablets to break in a specific plane. 
Tablet hardness is a useful parameter for in-process control and quality assurance.   
 
For chewable tablets, tablet hardness is also an important indicator for its suitability for use by 
the targeted patient population.  
 
Early publications have shown that the variations in fracture strength were due to inaccuracies of 
the instrumental scales of the various hardness testers as well as variations in the method of 
application of the load, physical dimensions, and shape of the tablet.38,39,40,41 Of the several 
approaches applied to measure tablet breaking strength, tensile strength measurement is indicated 
as a more reliable approach where variations due to the method are minimized. Tensile strength 
measurement is applied as a more fundamental measure of the tablets ability to withstand 
breaking force due to the inherent strength of the compacted material.42 
 
Two methods used for measuring tablet strength are: diametral compression (diametrical tensile 
strength) and flexural bending (flexure tensile strength test). The relationship between the two 
methods is explored to calculate a value which is described here as a chewing difficulty index.43 
 
A diametral tensile strength measurement is carried out for a flat disc-like tablet, taking into 
account its shape (round) and size (adjustment for its thickness), and can be described by 
Equation 1. While modified tensile strength equations for tablets with different shapes and sizes 
are available, the approach described here is for flat-faced round tablets.44,45,46  
 
The diametral tensile strength ( ) is calculated using the following equation:47 
h
                                                 
37 See footnote 8. 
38 Jarosz PJ and EL Parrott, 1982, Tensile Strength and Hardness of Tablets, J Pharm Sci, 71(6), 705-707. 
39 Podczeck F, 2012, Methods for the practical determination of the mechanical strength of tablets-From empiricism 
to science, Int J Pharm, 436, 214-232. 
40 Shang C, IC Sinka, B Jayaraman, J Pan, 2013, Break force and tensile strength relationship for curved faced 
tablets subject to diametrical compression, Int J Pharm, 442, 57-74. 
41 See footnote 10. 
42 David ST and LL Augsburger, 1974, Flexure Test for Determination of Tablet Tensile Strength, J Pharm Sci, 
63(6) 933-936. 
43 See footnote 14. 
44 See footnote 8. 
45 See footnote 10. 
46 Davies PN, HEC Worthington, F Podczeck, JM Newton, 2007, The determination of the mechanical strength of 
tablets of different shapes, Europ J Pharm Biopharm, 67, 268-276. 
47 Fell JT and JM Newton, 1970, Determination of tablet strength by the diametral-compression test, J Pharm Sci, 
59:688691. 
 
  10  Contains Nonbinding Recommendations 
2F
 = h               Equation 1 
h DH
where F  is the load required to break the tablet, D is the tablet diameter and H is the 
h
tablet thickness (see Figure A where the tablet is placed on its side). 
 
Equation 2 provides an alternate approach to calculate diametral tensile strength by flexural 
bending.  Tablet breaking force (F) using this tablet loading method for determining strength is 
f
also referred to as a three-point bending test and is measured by applying the breaking force by 
means of a straight edge to an unsupported midpoint of the top face of a tablet which is 
supported at the lower face of the tablet with two lower supports.42 The tensile strength () in 
f
this case may be calculated as:48 
3F L
 = f               Equation 2 
f 2DH2
where L is the constant distance between the two lower supports and the other terms are as 
defined earlier (see Figure B). For the three-point flexural tensile strength test, it is recommended 
that L=(2/3)D. 42,49,50  
 
Several publications have shown that depending on test conditions, the tensile strength values 
determined from the two test methods (diametral and flexural methods) have been shown to be 
proportional to each other. 
 
Thus,     
 = k                Equation 3 
f h
where k is the proportionality constant.  
 
Substituting equations 1 and 2 in equation 3, gives 
 
3F L 2F
    f =k h             Equation 4 
2DH2 DH
 
Rearranging Equation 4 gives the relationship between the forces F and F  as  
f h
3L
 F = F H             Equation 5 
 4k  f h
Since 3L/4 is an experimental constant, while k is a proportionality constant between the 
two tensile strengths, Equation 5 may be viewed as defining the parameters and their relationship 
as indicators of the Chewing Difficulty Index.  
 
                                                 
48 ASTM Standard D 0790-10, 2010, Standard Test Methods for Flexural Properties of Unreinforced and Reinforced 
Plastics and Electrical Insulating Materials, ASTM International, West Conshohocken, PA. 
49 Moser MA, M Krumme, PC Schmidt, 1998, Flexure Test of Tablets, Pharmazie, 53, 46-51. 
50 Stanley P, 2001, Mechanical strength of compacted powders, Int J Pharm, 227, 27-38. 
  11  Contains Nonbinding Recommendations 
If the diametral compression test is used for tensile strength measurement, the product of the load 
required to break the tablet (i.e., at failure) (F ) and tablet thickness (H) provide a measure of the 
h
difficulty of breaking/chewing the chewable tablets, as  
ChewingDifficultyIndex = F H       Equation 6 
h
 
FIGURES 
 
A) B)
F
h
F
f
D H
L
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  12  Contains Nonbinding Recommendations 
APPENDIX II:  SIMULATED SALIVARY FLUID COMPOSITION  
 
Currently, there is no official standard for the composition of simulated salivary fluid. Different 
compositions have been proposed in the literature.51 An example of simulated salivary fluid (pH 
6.8) is presented below.52 
 
 
Ingredient  Concentration (mg/L) 
Magnesium chloride, anhydrous (MgCl )    100 
2
Calcium chloride, dihydrate (CaCl 2H O)    220 
2 2
Sodium phosphate dibasic, heptahydrate (Na HPO 7H O)  1350 
2 4 2
Potassium phosphate monobasic (KH PO )    680 
2 4
Potassium chloride (KCl)    750 
Urea (CO(NH) )    600 
2
Sodium chloride (NaCl)    600 
De-ionized water    q.s. 
 
 
                                                 
51 Gal JY, Y Fovet, M Adib-Yadzi, 2001, About a synthetic saliva for in vitro studies, Talanta, 53:1103-1115. 
52 See footnote 14. 
  13