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.

Gerry McNally

	Although both share a preference for use of oral solid-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/consumer.  Recent trends in consumer-directed innovation in the OTC pharmaceutical market are summarized in 

	Differences between prescription and OTC products first became pronounced in the mid-1980s, when OTC manufacturers began to introduce increasingly diverse consumer-oriented 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 healthcare 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, appearance, 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 predominantly standard tablets or capsules with relatively few new delivery formats other than some modified-release products, the most unique being a slow-release nicotine chewing gum. 

	Introduction of more competitive and higher quality private-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 packaging design has remained constant, driven by competing OTC brands as well as generic-pharmaceutical 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 companies to differentiate products (1). 

	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 reflect patient compliance 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 excipients 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 analgesics. 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 expect more from OTC treatments. Continuous innovation in packaging and drug delivery formats is required if a new OTC franchise is to remain successful (3).

	Around 30 years ago, several sustained-release cough cold brands that had dosing of 12 hours, were developed and marketed, such as Drixoral (originally Schering-Plough’s trade name), and Delsym (Fison’s brand in the 1980s, but now Reckitt 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 dosing. Thus, Delsym and other legacy long-acting brands experienced 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 continuous form innovation, which included introducing novel gelatin-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 improving the taste of pediatric analgesics by replacing liquid formulations with suspensions, thus improving patient compliance. 

	For solid-dose formulations, taste-masked drug particles were incorporated into chewable tablets, which offered a convenient dosage form for both children and adults. Taste-masked drug particles also enabled the convenient powder pack dosage 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 (Sandoz’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 specialists and contract development and manufacturing organizations (CDMOs). Examples of successful partnerships within the OTC space included the RP Sherer Company (now Catalent), which owns and offers Liqui-Gel softgel technology 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 technology was the osmotic-controlled release oral delivery system (OROS), which was used to produce long-acting formulations of several antihistamines and decongestants. The decongestant 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 dissolving 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 disappeared from the OTC market. The German firm Hermes Pharma has recently been promoting consumer/patient-friendly dosage formats (4). 

	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 supplement, 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 products, using technology invented and produced by Raritan Pharmaceuticals (5). GlaxoSmithKline later leveraged the technology in its Theraflu PowerPods product line.

	The history of OTC pharmaceuticals clearly shows the importance 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) Theraflu 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 quality of products supplied to store brands and have matched most new formats introduced by the national brands. Innovative technology developed for branded OTCs is being copied, in ever shorter development 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. Considering 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 particularly 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-functional technical expertise and capability that many firms may no longer possess inhouse. 

	The economics of OTC pharmaceuticals depend on optimized 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. Examples exist across all unit operations. Innovations such as gelatin-coated dosage forms saw the utilization of capsule-manufacturing 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 standard in food and beverage categories, may be crucial for sustained success in OTC.

	The OTC industry has also leveraged technology from outside 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 confectionery formats have appeared across various consumer healthcare categories, taking innovations in candy manufacturing and applying them to pharmaceuticals. Novel excipients and new grades of existing excipients have also enabled the expedient 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 commercialized, or would have been cost prohibitive. 

	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 considering OTC innovations, it is important to assess areas of opportunity. 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 insights, it is important to keep in mind that the average consumer is most likely to provide feedback that will drive incremental innovations 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 current 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 behavior. 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, consumer 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 technologies entering the OTC market must offer a cost-effective alternative and must be positioned appropriately which requires deep consumer understanding and market knowledge. 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 easier 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 (6,7,8). Overall, sensory signals enhance the consumer experience. This is evident in the cough and 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 factors in consumer’s minds when they purchase a non-prescription 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 (

), 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 development 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. 

	5. V. Nayak, US Patent number 10,294,019, May 21, 2019.

	6. S. Stegemann, C. Lehmann, and M. Lowery, 

Supplement: Solid Dosage Drug Development and Manufacturing

	When referring to this article, please cite it as G. McNally, "Oral Dosage Form Innovation in OTC Pharmaceuticals," 

Pharmaceutical Technology Supplement: Solid Dosage Drug Development and Manufacturing

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A quick look at the history of OTC dosage form development shows the importance of patient-centered innovation.
