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Pharmaceutical Technology
SOLID DOSAGE DRUG D EVELOPMEN T AND MANU FACTURING 202 0 PharmTech.com
Development
A
lthough both share a preference for use of oral sol-
id-dosage forms, the business model for consumer
pharmaceutical manufacturers—often called over-
the-counter (OTC) manufacturers in the United
States—differs significantly from that of prescription drug
manufacturers. However, both types of companies have been
responding to market changes by focusing on formulation and
delivery changes that increase convenience to the patient/con-
sumer. Figure 1 summarizes recent trends in consu mer-directed
innovation in the OTC pharmaceutical market.
Differences between prescription and OTC products first
became pronounced in the mid-1980s, when OTC manufac-
turers began to introduce increasingly diverse consumer-ori-
ented products, and to change their approach to marketing,
promotion, and packaging. The OTC marketing approach
became more like that used in other fast-moving consumer
packaged goods (FMCG) industries (e.g., foods, beverages,
and personal care products). Packaging and advertising were
increasingly directed to the consumer, rather than the health-
care provider or pharmacist.
Emphasis on form and sensory attributes
During the 1990s, the marketing of dosage formats and
features such as form and sensory attributes (e.g.,colors, ap-
pearance, and flavors) became part of the product promotion
mix. Recently, a major growth driver for OTC pharmaceuticals,
particularly in the US, has been new products that resulted from
prescription-to-OTC switches. These products were predomi-
nantly standard tablets or capsules with relatively few new de-
livery formats other than some modified-release products, the
most unique being a slow-release nicotine chewing gum.
Introduction of more competitive and higher quality pri-
vate-label or store-brand products in the 1990s underscored
the need for branded OTC manufacturers to differentiate their
offerings. The pressure to innovate with dosage form and pack-
aging design has remained constant, driven by competing OTC
brands as well as generic-pharmaceutica l companies that supply
drug stores and supermarkets with copies of branded products.
Retailer consolidation has also driven increased competition,
and dosage form innovation has become a crucial way for com-
panies to differentiate products (1).
Gerry P. McNally is principal of McNally Consulting
Group, LLC. With more than 25 years of experience,
he earned a BS and PhD in chemistry from University
College, Dublin, Ireland and holds more than 25 patents
in drug delivery and formulation. He can be reached at
gmcnally47@aol.com.
PHAT1978 - STOCK.AD OBE.COM
Oral Dosage Form Innovation
in OTC Pharmaceuticals
Gerry McNally
A quick look at the history of OTC dosage
form development shows the importance
of patient-centered innovation.
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Pharmaceutical Technology
SOLID DOSAGE DRUG D EVELOPMEN T AND MANU FACTURING 202 0 PharmTech.com
Greater consumer focus in OTC products
Both product packaging and delivery form have become key
differentiators for OTC products. Traditional syrup, tablet, and
capsule formats have made way for a diverse array of forms such
as softgels, gelcaps, chewing gums, powders, effervescent tablets
for hot and cold drinks, as well as orally disintegrating tablets
and confectionery-derived forms.
A number of considerations go into the consumer’s buying
decision (2). Delivery format may often ref lect patient compli-
ance issues, especially for pediatric formulas, but perceptions
of efficacy and consumer preference are also crucial. More
complex OTC formulations and delivery systems often require
unique manufacturing technology and almost always involve
complex analytical methodologies due to the additional excip-
ients used in the formulations.
Most orally administered products that switched from
prescription to OTC did not introduce new delivery formats.
However, many brought significant consumer benefits (e.g., less
frequent dosing) to existing categories such as longer-acting an-
algesics. An example would be Bayer’s longer lasting Aleve.
They also created new paradigms for consumers (e.g., once
daily dosing for heartburn and seasonal allergy treatments).
These product introductions greatly increased the consumer’s
awareness and understanding of the benefits of longer-acting
remedies and less-frequent dosing. As a result, consumers ex-
pect more from OTC treatments. Continuous innovation in
packaging and drug delivery formats is required if a new OTC
franchise is to remain successful (3).
More convenient dosing
Around 30 years ago, several sustained-release cough cold
brands that had dosing of 12 hours, were developed and mar-
keted, such as Drixoral (originally Schering-Plough’s trade
name), and Delsym (Fison’s brand in the 1980s, but now Reck-
itt Benckiser’s [RB’s]). These products may have been ahead of
their time because most OTC products in the mid-1980s were
dosed at a 4–6-hour frequency. It was not until the 1990s, after
several longer-acting drugs switched from prescription to OTC,
that consumers became familiar with once- or twice-daily dos-
ing. Thus, Delsym and other legacy long-acting brands expe-
rienced something of a renaissance in the late 1990s and early
2000s.
Johnson & Johnson’s Tylenol analgesic brand maintained a
strong market presence over several decades, due to continu-
ous form innovation, which included introducing novel gela-
tin-coated, capsule-shaped tablets called gelcaps, with a later
addition of gelatin-coated round tablets called geltabs. In the
mid 2000s, Tylenol gelcaps were replaced by rapid-release gels,
gelatin-coated caplets with laser-drilled holes that enabled faster
disintegration and dissolution. Other innovations included im-
proving the taste of pediatric analgesics by replacing liquid for-
mulations with suspensions, thus improving patient compliance.
For solid-dose formulations, taste-masked drug particles
were incorporated into chewable tablets, which offered a con-
venient dosage form for both children and adults. Taste-masked
drug particles also enabled the convenient powder pack dos-
age format introduced in 2019 as Children’s Tylenol dissolve
packs. Another innovation in the cough/cold category was the
hot-drink format first introduced in the UK under the Lemsip
brand(now owned by RB) and later in the US as Theraflu (San-
doz’s brand in the 1990s but GlaxoSmithKline’s today).
Technology licensing and development partnerships
Increasing competition in consumer pharmaceuticals and
limited resources for developing innovative forms inhouse
paved the way for partnerships between drug delivery spe-
cialists and contract development and manufacturing or-
ganizations (CDMOs). Examples of successful partnerships
within the OTC space included the RP Sherer Company (now
Catalent), which owns and offers Liqui-Gel softgel technol-
ogy for license (using its OptiGel technology in-house) and
Zydis, the first orally disintegrating tablet (ODT) to use freeze
drying technology. One of the first commercially significant
branded OTC Liqui-Gel introductions was for the cough and
cold treatment, Vicks’ Nyquil/Dayquil (Proctor and Gamble),
and was followed by Advil (now GSK’s, but originally Wyeth’s
and later Pfizer’s) Liqui-Gel for pain relief.
ALZA Corporation was another notable drug delivery
company to supply the OTC industry with novel oral and
transdermal drug delivery technologies. The oral technol-
ogy was the osmotic-controlled release oral delivery system
(OROS), which was used to produce long-acting formulations
of several antihistamines and decongestants. The deconges-
tant product is still on the market today under the Sudafed 24-
Hour brand (Warner Lambert’s technology when launched,
but now Johnson & Johnson’s).
Other unique forms introduced by third-party collaborations
included fast orally dissolv ing films (ODFs), which enjoyed a level
of market success following the launch of Listerine pocketpaks
(originally Warner Lambert’s trade name but now J&J’s) in 2001.
However, since then, this format has all but disappea red from the
OTC market. The German firm Hermes Pharma has recently
been promoting consumer/patient-friendly dosage formats (4).
Development
Figure 1. Innovation in over-the-counter oral solid dosage
delivery forms (1990 - 2020)
FIGURE COURTESY OF THE AUTHOR.
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Pharmaceutical Technology
SOLID DOSAGE DRUG D EVELOPMEN T AND MANU FACTURING 202 0 PharmTech.com
A recent trend has been the development and manufacture of
various confectionery pharmaceutical forms such as soft chews
and gummies; the United States Pharmacopeial nomenclature
is “chewable gel.” The gummy form was first introduced in the
pediatric vitamin category but soon became a favorite with adult
OTC formulations, and is currently used in vitamin and sup-
plement, as well as antacid, laxative, and probiotic treatments.
The pharmacy chain CVS recently introduced a Keurig (K-
Cup) formulation of the traditional hot drink cold relief prod-
ucts, using technology invented and produced by Raritan Phar-
maceuticals (5). GlaxoSmithKline later leveraged the technology
in its Theraflu PowerPods product line.
The unique importance of dose format
The history of OTC pharmaceuticals clearly shows the impor-
tance of dosage form to the consumer. Several OTC brands have
been created based on a core drug-delivery platform, including
RB’s Lemsip and GlaxoSmithKline’s (GSK’s) (formerly Sandoz’s)
Theraf lu cough and cold brands (powders for dissolution in hot
water) and RB’s (formerly Adams’) Mucinex (12- and 24-hour
guaifenesin and guaifenesin combination products).
The importance of dosage-form and value-added innovation
in OTC lifecycle management cannot be overstated. Generic
manufacturers have noticeably improved the qua lity of products
supplied to store brands and have matched most new formats
introduced by the national brands. Innovative technology devel-
oped for branded OTCs is being copied, in ever shorter develop-
ment timeframes, by fiercely competitive generic drug suppliers.
Based on the broad acceptance of generic drug products and
the slowing pace of innovation from the national brands, it is
likely that the share of store brands will continue to grow. Con-
sidering the decrease in major new prescription-to-OTC switch
candidates, it is more important now than ever that consumer
healthcare companies innovate in new delivery formats.
This has long been the challenge for older molecules partic-
ularly those that have been on the market for 30 years or more.
The significant innovation in formats driven by the consumer
healthcare companies in the analgesic, upper respiratory, and
gastrointestinal categories was one of the key strategies to drive
growth and protect market share of older drugs. At the same
time, developing proprietary forms that appeal to consumers
has become more difficult and requires a depth of cross-func-
tional technical expertise and capability that many firms may
no longer possess inhouse.
The economics of OTC pharmaceuticals depend on opti-
mized manufacturing processes, and it is clear that efficiencies
gained from scale allow leading players to be cost competitive
with both base products and new technology platforms. OTC
companies have leveraged pharmaceutical processes and scaled
them for large volume, lower-cost OTC drug products. Exam-
ples exist across all unit operations. Innovations such as gela-
tin-coated dosage forms saw the utilization of capsule-manufac-
turing technology being applied in a new way to make a novel
solid dosage form that has gained wide acceptance. In the future,
continuous processing, already a sta ndard in food and beverage
categories, may be crucial for sustained success in OTC.
The OTC industry has also leveraged technology from out-
side of oral solid dose manufacturing, as evident in the softgel
form. Borrowing from transdermal drug delivery technology
gave rise to oral film strips, while a growing number of con-
fectionery formats have appeared across various consumer
healthcare categories, taking innovations in candy manufac-
turing and applying them to pharmaceuticals. Novel excipients
and new grades of existing excipients have also enabled the ex-
pedient formulation and commercialization of several dosage
forms (e.g., directly compressed ODTs). Development of many
directly compressible grades of active ingredients have helped
OTC manufacturers innovate less expensively.
Meanwhile, advances in coating polymers have enhanced the
ability to taste mask bitter active ingredients more effectively
while at the same time lowering production costs. There have
also been major advances in sensorially important ingredients
such as flavors, sensates, high-potency sweeteners, and elegant
tablet coating polymer systems, all of which must comply with
increasingly stringent regulatory requirements. Without the
significant advances in many areas of analytical and stability
science, many innovations might never have been commercial-
ized, or would have been cost prohibitive.
Understanding the consumer
Consumer benefits associated with various dosage formats such
as ease of swallowing, appearance, convenience, portability, and
taste have been shown to be important (4,6,7). When consider-
ing OTC innovations, it is important to assess areas of opportu-
nity. This may involve looking at gaps in the marketplace, how
important a particular dosage form is to the end user, and how
satisfied they are with the existing formats. In gathering such in-
sights, it is important to keep in mind that the average consu mer
is most likely to provide feedback that will drive incremental in-
novations based on his or her understanding of what is already
available. To be successful, the OTC development scientist and
formulator should, ideally, have a good understanding of cur-
rent consumer trends, not only in healthcare but in the FMCG
category overall. Factors such as convenience, customization,
and the role and impact of on-line marketing and selling are all
broad trends that should inform product development.
Changes in demographics such as the aging population may
also present opportunities for new insights into consumer be-
havior. When consumers have a clear need, their preferences
will lead dosage form development, as they have with gummy
and soft chew formats in certain supplement categories.
Although it may be time consuming and expensive, con-
sumer testing and validation is critical to ensuring success.
This may require conducting test markets or pilot launches
in several cities to uncover product flaws or aspects that can
be optimized. This approach can offer valuable insights to
improve products and avoid costly product failures down
the road. Ultimately, consumers are looking for value and
for new products that satisfy an unmet need. New technol-
ogies entering the OTC market must offer a cost-effective
Development
Pharmaceutical Technology
SOLID DOSAGE DRUG D EVELOPMEN T AND MANU FACTURING 202 0 s9
alternative and must be positioned appropriately which re-
quires deep consumer understanding and market knowl-
edge. Core value-added benefits offer consumers something
distinctive such as faster onset or longer duration of action.
Other benefits may include reduced side effects, improved
taste/sensory performance for pediatric medicines, and eas-
ier dosing/convenience. Differentiating value-added benefits
may be designed into products. They reinforce the product
experience and emphasize a “reason to believe.” A good
example is liquid-filled capsules or softgels that connote
faster acting (6,7). Overall, sensory signals enhance the con-
sumer experience. This is ev ident in the cough a nd cold category,
where forms such as cooling liquids, hot soothing drinks, and
well-flavored lozenges all enhance the medicating experience
and give consumers confidence in the product.
In short, dosage format is critically important to the success
of branded OTC pharmaceuticals. It is one of the deciding fac-
tors in consumer’s minds when they purchase a non-prescrip-
tion drug product. To ensure continued growth of both mature
and newly switched OTC brands, innovator companies must
diligently pursue an aggressive life cycle management strategy
encompassing patent-protected dosage forms in conjunction
with protectable claims and packaging innovation.
In recent years, innovation in OTC oral delivery formats
has slowed (Fi gur e 1) , due in part to increased pressure on profit
margins. Many parent pharmaceutical companies are focusing
on a limited number of standardized manufacturing platforms.
At the same time, many of the drug delivery companies and
CDMOs that partnered with companies on OTC product de-
velopment are now focusing on more profitable niches in the
prescription drug business, and on biologics and innovative
treatments such as cell-and gene-based therapies. It is clear that
consumers will continue to select and purchase what they see
as the more user friendly dosage formats. What remains to be
seen is whether innovation will continue to be seen in nationally
branded products, or whether it will be taken over by disruptive
innovators such as new brands or store brands, a trend that has
already begun in some product categories.
References
1. P.R. Goggin, International Journal of Pharmaceutics, 469 (2), 254-
256 (2 014).
2. E. Kohli and A. Buller, Southern Medical Journal, 106 (2), Feb-
ruary 2013.
3. H. Albrecht and B. Nissen, Tablets and Capsules, 13 (5),2015.
4. T. Hein, Tablets and Capsules, 13 (6), 2015.
5. V. Nayak, US Patent number 10,294,019, May 21, 2019.
6. S. Stegemann, C. Lehmann, and M. Lowery, Tablets and Capsules,
9 (1), 2011.
7. W. Jones and J. Francis, Advanced Therapy, 17 (5), 213-221 (2001).
8. B. Locwin, Tablets and Capsules, 9(1), 2011.