Oral Disintegrating Tablets Make Dosing Challenges for Children Disappear
Pediatric patients present unique challenges when it comes to
administering medications. Solid oral dosing forms are particularly
difficult for this population; children under four cannot swallow
tablets, and capsules are often not an option until after 12 years of
age. Many young patients also experience a fear of choking that can make
taking any kind of pill nearly impossible.1
To overcome these issues, liquid formulations have been the standard
dosing form for children. However, liquids have shortcomings of their
own. Solubility can be an obstacle for both the excipients and the
active ingredients, and stability may present a problem when a drug
requires taste-masking additives or preservatives.
In addition, liquid medications are particularly vulnerable to dosing
errors. A study conducted by Regions Hospital in St. Paul, Minn.,
illustrated how prevalent these mistakes can be. In this study, the most
commonly used dosing device was the household teaspoon. However, this
tool is hardly accurate, as teaspoons can vary in volume from 2 mL to 10
mL. Even using the same spoon, different users can deliver doses
ranging from 3 mL to 7 mL. Consequently, since 1975, the American
Academy of Pediatrics has strongly recommended against using household
teaspoons for measuring liquid medications.2
Specially designed dosing devices such as dosing cups and cylindrical
spoons appear promising but do not solve the problem. In the Minnesota
study, some participants confused the markings on a dosing cup for
teaspoons and tablespoons, and the cylindrical spoon increased the risk
Similar to the action of a cotton candy
machine, centrifugal action creates a floss which is then cooled,
partially recrystallized, and finally compressed into ODTs.
Another potential dosing error can result from misinterpreting the
dosing chart on the liquid medication package. If a child’s weight is
discordant with his/her age, the weight should be used to determine the
correct dose. However, parents or caregivers may use the child’s age,
resulting in either an overdose or a therapeutically inadequate amount.
Beyond dosing accuracy, another challenge presented by liquids is
taste masking. When drug developers are choosing medication flavors to
cover the taste of an active ingredient, they must consider the fact
that the pediatric palate responds to flavors very differently than that
of an adult. Choosing tastes is made more complicated by cultural
factors—different flavors are favored by the populations of different
countries, and medications incorporating flavors that are regionally
popular are considered more palatable in those regions. But, while a
pleasant taste can help with compliance, manufacturers must be careful
to avoid encouraging overconsumption by making medicine taste too much
like a sweet treat.3
Newer dosing forms have emerged to meet the challenges posed by
pediatric patients. One technology is the oral disintegrating tablet, a
solid dosing form that disintegrates in the mouth within five to 30
seconds without chewing or liquids. Because this type of formulation
does not require swallowing, it offers a significant advantage for
children. In addition, the drug can be absorbed in multiple places in
the gastrointestinal tract, from the pharynx down, resulting in greater
bioavailability than traditional oral dosing technologies.4-6 continues below...
Case Study: Fast-Acting Oral Thin Films Show Promise
Another oral delivery system that can effectively meet the challenges
of the pediatric population is the oral thin film. These
fast-dissolving, mucoadhesive films are composed of the active
ingredient, polymers, plasticizers, and surfactants, along with colors
and flavorings to make the experience palatable. OTFs usually measure
between 2 and 8 cm2 and are placed on or under the tongue, where they
rapidly dissolve and release the drug at the application site.1,2
In addition to overcoming the pediatric swallowing challenge, OTFs
offer several advantages over ODTs and conventional oral delivery
systems. They can provide increased bioavailability for some drugs,
potentially improve the onset of action, decrease dosing, and enhance a
drug’s efficacy and safety profile. They can also be produced at a cost
competitive with that of conventional tableting.
There are numerous methods used to manufacture these minty-flavored
wafers. The preferred method is solvent casting, because it employs
equipment already common throughout the pharmaceutical manufacturing
world. Water-soluble ingredients are dissolved to form a viscous
solution; then the active ingredient is dissolved in a small amount of
the solution. The solution containing the drug is then mixed with the
viscous solution, and any entrapped air is vacuumed out. The final
solution is cast as a film, dried, and cut into pieces.3
There are several challenges to achieving commercial scale
production of OTFs. A key factor in the process is reaching sufficiently
rapid speeds in the coating and drying operations. This can be
facilitated by employing enough dryers of the correct type, either
horizontal-nozzle, bow, or hot-flue.
Another important consideration for production is taking the proper
measures to prevent air and moisture from becoming entrapped in the
film. Air in the OTFs would produce an uneven surface, and water would
affect properties such as tensile strength, flexibility, and folding
OTFs offer the pharmaceutical industry an attractive alternative to
oral dosing form. They are portable, easy to use, and convenient, and
they can be manufactured on equipment already used by drug
Malke S, Shidhaye S, Desai J, Kadam V. Oral films – patient
compliant dosage form for pediatrics. The Internet Journal of Pediatrics
and Neonatology. Available at: www.ispub.com/journal/the-internet-journal-of-pediatrics-and-neonatology/volume-11-number-2/oral-films-patient-compliant-dosage-form-for-pediatrics.html. Accessed March 13, 2012.
Arya A, Chandra A, Sharma V, Pathak K. Fast dissolving oral films: an innovative drug delivery system and dosage form. Int J ChemTech Res. 2010;2(1):576-583.
Greb E. Are orally dissolving strips easy for manufacturers to swallow? PharmTech.com. Jan. 21, 2009. Available at: http://license.icopyright.net/user/viewFreeUse.act?fuid=MTU0OTgxMTg%3D. Accessed March 13, 2012.
The ODT dosing form is a viable option for numerous active
ingredients. As long as a drug is water soluble, is permeable, and can
be dosed at less than 20 mg, it is a candidate for delivery as an ODT.
Taste is an important factor as well—because the tablet is dissolving in
the mouth, it must be possible to mask the drug’s taste.7
Several widely prescribed pediatric medications are currently
marketed as ODTs: Prevacid, an antiulcerative; Zofran, an antiemetic
indicated to prevent the nausea and vomiting associated with
chemotherapy; and Clarinex RediTabs, an antihistamine. In addition to
these prescription brands, OTC products include Claritin RediTabs,
Alavert, and Triaminic.
There are two main types of ODT formulations. The first is a loosely
compressed tablet manufactured using conventional tableting technology
with lesser degrees of compaction, combined with water-soluble
excipients and/or powerful disintegrants. The second type is a very
porous, lyophilized (freeze-dried) formulation. Both categories exploit
the rapid uptake of saliva to achieve fast disintegration.
There are numerous processes used to manufacture the loosely
compressed ODTs. One popular method is called the cotton candy process.
The active ingredient is combined with sugar alcohols such as mannitol
or sorbitol and melted. Similar to the action of a cotton candy machine,
centrifugal action creates a floss which is then cooled, partially
recrystallized, and finally compressed into ODTs.
The lyophilization process involves trapping a drug in a matrix of
fast-dissolving excipients including saccharides, gums and collapse
Another method combines super disintegrants with
highly volatile ingredients such as camphor or menthol. Once the active
ingredient is added, the mixture is compressed into tablets and the
volatile substances are removed by sublimation, leaving a very porous
and easily disintegrating ODT. A simpler technique involves blending
sugar alcohols with active ingredients and excipients, including
solidifying agents, and then melting them together. The molten mixture
is then poured into blister packaging wells and dried.
Alternatively, the lyophilization process involves trapping a drug in a matrix of fast-dissolving excipients including:
Saccharides to add hardness and pleasant texture;
Gums to impart stability; and
Collapse protectants to prevent long-term shrinkage.
The ingredients are dissolved in water and the solution is poured
into blister packs—or another unit dosing form—and freeze dried. This
process avoids heating, making it suitable for drugs that would be
adversely affected by elevated temperatures.
U.S. Department of Health and Human Services. Development of
appropriate pediatric formulations and drug delivery systems SBIR (R43)
application. Available at: http://grants.nih.gov/grants/guide/pa-files/PAR-11-304.html. Accessed March 13, 2012.
Madlon-Kay DJ, Mosch FS. Liquid medication dosing errors. The Journal of Family Practice online. Available at: www.jfponline.com/Pages.asp?AID=2582. Accessed March 13, 2012.
Gauthier P, Cardot JM. Developing drugs for children and the
adjustment of medication – is it a new challenge or an adaptation of
past ideas? Journal of Personalized Medicine online. Available at: www.mdpi.com/2075-4426/1/1/5/. Accessed March 13, 2012.
Banbury S, MacGregor K. Fast-dispersing dosage forms for the pediatric market. Drug Deliv Technol. 2011;11(2):32-35.
Stoltenberg I, Winzenburg G, Breitkreutz J. Solid oral dosage
forms for children – formulations, excipients and acceptance issues.
Journal of Applied Therapeutic Research. Available at: www.euromedcommunications.com/files/products/Stoltenberg%20Winzenburg%20Breitkreutz.pdf. Accessed March 13, 2012.
Goel H, Rai P, Rana V, Tiwary A. Orally disintegrating systems: innovations in formulation and technology. Recent Pat Drug Deliv Formul. 2008;2(3):258-274.
Strickley RG, Iwata Q, Wu S, Dahl TC. Pediatric drugs – a review of commercially available oral formulations. J Pharm Sci. 2008;97(5):1731-1774.
Parkash V, Maan S, Yadav SK, et al. Fast disintegrating tablets: Opportunity in drug delivery system. J Adv Pharm Technol Res. 2011;2(4):223-235.
Ascher-Svanum H, Furiak NM, Lawson AH, et al. Cost-effectiveness
of several atypical anti-psychotics in orally disintegrating tablets
compared with standard oral tablets in the treatment of schizophrenia in
the United States [published online ahead of print Feb. 21, 2012]. J Med Econ.
Solanki SS, Dahima R. Formulation and evaluation of aceclofenac mouth-dissolving tablet. J Adv Pharm Technol Res. 2011;2(2):128-131.
Kondo K, Niwa T, Ozeki Y, Ando M, Danjo K. Preparation and
evaluation of orally rapidly disintegrating tablets containing
taste-masked particles using one-step dry-coated tablets technology. Chem Pharm Bull (Tokyo). 2011;59(10):1214-1220.
Gryczke A, Schminke S, Maniruzzaman M, Beck J, Douroumis D.
Development and evaluation of orally disintegrating tablets (ODTs)
containing ibuprofen granules prepared by hot melt extrusion. Colloids Surf B Biointerfaces. 2011;86(2):275-284.