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 CONTENTSI.

INTRODUCTION............................................................................................................. 1II.

BACKGROUND ............................................................................................................... 2

III.

DISCUSSION .................................................................................................................... 2

A.

Hardness ......................................................................................................................................... 3

B.

Disintegration ................................................................................................................................. 3

C.

Dissolution ...................................................................................................................................... 4D.

Performance in Simulated Physiological Media ......................................................................... 4E.

Use of In Vitro Bioequivalence Data and Postapproval Considerations .................................. 5IV.

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 ROUNDTABLETS ........................................................................................................................ 10
FIGURES ..................................................................................................................................... 12
APPENDIX II: SIMULATED SALIVARY FLUID COMPOSITION ................................ 13

Contains Nonbinding Recommendations

Quality Attribute Considerations for Chewable Tablets
Guidance for Industry 1
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 thetitle page.

I.

INTRODUCTION

This guidance provides manufacturers of chewable tablets 2 for human use with the Center for
Drug Evaluation and Research’s (CDER) current thinking on the critical quality attributes thatshould 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, FDA’s guidance documents do not establish legally enforceable responsibilities.
Instead, guidances describe the Agency’s 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 andResearch 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 asprescription 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 designand 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 therecommendations in this guidance.
5
This guidance should be considered for CMC supplements submitted for modifications that affect the formulationor other critical quality attributes of a chewable tablet.

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Contains Nonbinding RecommendationsII.

BACKGROUND

Chewable tablets are an oral dosage form intended to be chewed and then swallowed by thepatient 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, easyto-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 ofchewable tablets: (1) those that may be chewed for ease of administration, and (2) those thatmust 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 ofthese reported adverse events, the Agency reviewed approved drug product applications forchewable tablets and found that in certain cases critical quality attributes such as hardness,disintegration, and dissolution were not consistently evaluated. This was evidenced by instancesof 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 analyticalprocedures 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 andmeaningful 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 forchewable tablets. An ideal chewable tablet should be:•

Easy to chew

6

USP-NF <1151> Pharmaceutical Dosage Forms.
For general information on collection of Adverse Event Reports by FDA, see
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/default.htm.
8
USP-NF < 1217> Tablet Breaking Force.
9David ST and LL Augsburger, 1974, Flexure test for determination of tablet tensile strength, J Pharm Sci, 63:933936.
10
Ambros MC, F Podczeck, H Podczeck H, JM Newton, 1998, The characterization of the mechanical strength ofchewable tablets, Pharm Dev Tech, 3:509-515.
72

Contains Nonbinding Recommendations•••

Palatable (taste masked or of acceptable taste)
Of appropriate size and shape 11
Able to disintegrate readily to facilitate dissolution

Critical quality attributes for chewable tablets should include hardness, disintegration, anddissolution, 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., apatient 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 theperformance 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 specificplane. Public standards exist to ensure consistent measurement of the tablet hardness (Tablet
Breaking Force 12). 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 tocreate 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 the11

For tablets that may be chewed or swallowed whole, the guidance for industry Size, Shape, and Other PhysicalAttributes 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 thatthe 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 athttps://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.

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Contains Nonbinding Recommendations
event a tablet is not completely chewed by the patient. Usually, the presence of the correct typeand amount of a disintegrant facilitates rapid disintegration of the tablet. In vitro disintegration
testing should be conducted using intact tablets in suitable medium using establisheddisintegration 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 theintact 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 establisheddissolution 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 MediaA 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 criticalquality attributes.
16

USP-NF <701> Disintegration.
See guidance for industry Dissolution Testing of Immediate Release Solid Oral Dosage Forms. When final, thisguidance will represent the FDA’s 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 andBiopharm, 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.
17

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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 thedevelopment of a chewable tablet.
A.

Patient Acceptability and In vivo Performance

Potential product design and development considerations should include disintegrant(s) tofacilitate release of the active ingredient, and sweeteners and flavoring agents for tastemasking. 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 subject’s 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 achoking 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.

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Contains Nonbinding Recommendations

For ANDA applications for which in vivo bioequivalence studies are conducted, general
information such as the subject’s sensory experience (acceptability of taste, mouthfeel, andaftertaste) 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 andpermeability characteristics of the drug substance, its stability in saliva (over a pH range 6.0 to7.5), and whether it undergoes extensive first-pass metabolism.
Stability in the buccal environment can usually be assessed in vitro. For example, studies at theapplicable pH range over a short period of time (e.g., <5 min) showing minimal drug substancerelease 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 productspecification. 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 Stepsand 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 (seeAppendix 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 product’s 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 isdifficult to chew (e.g., causes damage to teeth or dentures, or GI obstruction), the Agency willcommunicate 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.

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Contains Nonbinding Recommendations•

Hardnesso Based on the review of applications and literature sources, the Agency
recommends that hardness for chewable tablets be kept low (e.g., <12 kp). 33
o A higher hardness value (e.g., >12 kp) may be considered if justified. An
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 inwhich the tablet is exposed to a small quantity (e.g., 1 mL) of simulated
salivary fluid (see Appendix II) for 30 seconds.
o In all other cases, the sponsor/applicant should provide justification for the
proposed hardness, including studies demonstrating that the tablet can bereadily chewed by the intended population without GI obstruction, damage toteeth or dentures, or other adverse events related to chewing these tablets.
o In addition to evaluating the hardness of chewable tablets, thesponsor/applicant should consider evaluating the tablets for the chewing
difficulty index (see Appendix I) both before and after exposure to humansaliva.

•Disintegration and Dissolution
o Chewable tablets should typically meet the same disintegration anddissolution specifications as IR tablets.
o In vitro dissolution testing should be conducted on intact chewable tablets
since it is possible that some patients might swallow the tablets withoutchewing. Crushing of the chewable tablets prior to conducting in vitro
dissolution testing generally is not recommended since there is currently noreported 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.
o It is possible to use other methods, as long as the proposed methods aredemonstrated 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.

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Contains Nonbinding Recommendations•

Other Critical Quality Attributeso If other critical quality attributes are applicable to a particular chewable tablet,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 functionallycoated particles, it is important to ensure the functional coating continues toperform 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 theactive 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 labelingfor 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 theprinciple display panel with lesser prominence to reinforce the importance of chewing thetablets:
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.
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, andcarton/container labeling.
35

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Contains Nonbinding Recommendations
accompanying patient labeling (e.g., Medication Guide, Patient Package Insert, Instructions
for Use) if applicable.

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APPENDIX I: CHEWING DIFFICULTY INDEX FOR FLAT-FACED ROUNDTABLETS
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 indicatedas a more reliable approach where variations due to the method are minimized. Tensile strength
measurement is applied as a more fundamental measure of the tablet’s ability to withstandbreaking 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 (σh) is calculated using the following equation: 47

37

See footnote 8.
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.
42David 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 oftablets 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,
59:688–691.
38

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2Fh
Equation 1
πDH
where “Fh” is the load required to break the tablet, “D” is the tablet diameter and “H” is thetablet thickness (see Figure A where the tablet is placed on its side).

σh =Equation 2 provides an alternate approach to calculate diametral tensile strength by flexural
bending. Tablet breaking force (Ff) using this tablet loading method for determining strength isalso referred to as a three-point bending test and is measured by applying the breaking force bymeans 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 (σf) in
this case may be calculated as: 48
3F f Lσf =Equation 2
2 DH 2where “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,

σ f = kσ hEquation 3

where “k” is the proportionality constant.
Substituting equations 1 and 2 in equation 3, gives

3F f L
2 DH

2

=k

2 Fh
πDH

Equation 4

Rearranging Equation 4 gives the relationship between the forces Ff and Fh as 3πL 
 F f = Fh H
 4k 

Equation 5

Since “3πL/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 relationshipas 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.

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If the diametral compression test is used for tensile strength measurement, the product of the loadrequired to break the tablet (i.e., at failure) (Fh) and tablet thickness (H) provide a measure of the
difficulty of breaking/chewing the chewable tablets, as

Chewing Difficulty Index = Fh H
FIGURES
A)

B)

Fh

Ff
H

D
L

12

Equation 6

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 (pH6.8) is presented below. 52

IngredientConcentration (mg/L)

Magnesium chloride, anhydrous (MgCl2)
Calcium chloride, dihydrate (CaCl2⋅2H2O)
Sodium phosphate dibasic, heptahydrate (Na2HPO4⋅7H2O)
Potassium phosphate monobasic (KH2PO4)
Potassium chloride (KCl)Urea (CO(NH)2)
Sodium chloride (NaCl)
De-ionized water

51
52

100
220
1350
680
750
600
600
q.s.

Gal JY, Y Fovet, M Adib-Yadzi, 2001, About a synthetic saliva for in vitro studies, Talanta, 53:1103-1115.
See footnote 14.

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