OSD’s: The OG in Drug Formulation

Modern tablet production dates back to the 19th Century, but the technology has challenged formulators since ancient Egypt. George Griffenhagen, a renowned pharmaceutical historian, dates pills back to 1500 BC, assumedly invented so that measured amounts of a medicinal substance could be delivered to patients. The first pill references crop up in ancient Egyptian times, writes Griffenhagen, where papyruses were filled with medical remedies. Plant powders or other active ingredients would be mixed with dough, grease, or honey, then formed into balls with the fingers. In medieval times, pills began to be coated with slimy plant substances to slide down more easily or taste less bitter. Medicines in pill form became popular in 17th Century England and eventually made their way to the United States in the 18th Century. The 19th Century bore witness to sugarcoating and gelatin coating of pills, as well as the invention of gelatin capsules.¹

Our history with oral solid dosage formulations has given rise to a global oral solid dosage pharmaceutical market. The US alone accounted for 93.6% of the North American oral solid dosage pharmaceutical market share in 2021, owing to the increasing number of oral solid dosage drug approvals in the country. Of the 50 new drugs approved by CDER in 2021, almost half were tablets and capsules (23 in total).²

The OSD category is made up of tablets, capsules, powders and granules, lozenges and pastilles, and gummies. But it is tablets that continued to hold the maximum market share of 53.1% in 2021. This is due in part to their affordability, patient preference, and improved efficiency. Similarly, the global capsule market is expected to grow at a compound annual growth rate of 8.1% from 2021 to 2030, amounting to approximately 700 billion units every year around the world.³

Recent developments are taking oral solid dosage solutions to new heights. Innovation is being driven by the need to differentiate and to deliver sustainable, advanced products in a crowded pharmaceutical space.³ Some trends to watch for include:

One area of the OSD market expected to expand is the development and manufacturing of highly potent active pharmaceutical ingredients (HPAPIs). Immuno-oncology is one of the fastest-growing therapeutic development areas globally. In the US alone, this market is expected to grow from $63.9 billion in 2020 to $163 billion in 2027. Thus, roughly one-quarter of the drugs currently in development worldwide are being categorized as highly potent. Only a few CDMOs have the facilities, equipment, and specialized personnel to handle (HPAPI).⁴

There is growing demand for bi-layered tablets because of the potential to reduce the pill burden by administering two or more active pharmaceutical ingredients in a single fixed-dose combination form. These tablets can be engineered to prevent the direct contact of two drugs, increasing the efficacy of the two drugs through combination while maintaining stability of both drugs. They can be designed to modify release, wherein one layer can be modified as immediate-release and the other as an extended-release. Bi-layered tablets offer advantages like: prolonging the patent life of a drug product, increased efficacy of the active components due to their additive or synergistic effect, reduced toxicity, improved patient adherence, and convenience of use.⁵

The first 3D-printed drug product was approved for use in 2015. 3D-printed tablets have the potential to deliver large drug payloads rapidly — owing to their porous nature — and with minimal amounts of liquid. Opportunities for customization is a primary driver.²

The first 3D-printed drug product was approved for use in 2015. 3D-printed tablets have the potential to deliver large drug payloads rapidly — owing to their porous nature — and with minimal amounts of liquid. Opportunities for customization is a primary driver.²

The personalization of medicine is increasing demand for OSD forms that are customized to specific populations (patients of a certain age, gender, or body mass index, or even for individuals).²

Animal-based gelatin capsules are gradually being replaced by those made from materials of vegetarian sources such as cellulose-based polymer. This trend is becoming popular due to the increasing number of people choosing to lead a vegan or vegetarian lifestyle. Plant-based capsules, such as HPMC (hydroxypropyl methylcellulose), have been developed to cater to the needs of these vegan or vegetarian customer bases.

These trends are certain to drive the need for increased OSD manufacturing capacity now and for the foreseeable future.⁴

1. The Colorful History of Pills Can Fill Many a Tablet, Rosie Mestel, Los Angeles Times, March 25, 2002.
2. Dissolution testing: an established technique driving advances in drug delivery, Manufacturing Chemist, July 12, 2022.
3. Manufacturing OSD Forms: Key Trends Shaping the Industry, Laxman Shetty, et. al., Pharmaceutical Technology, May 15, 2022.
4. High Potency Active Pharmaceutical Ingredient (HPAPI) Market is Driven by Growing Preference for Outsourcing of HPAPI Manufacturing, Biospace, Aug. 9, 2022.
5. Formulation and Evaluation of Bi-Layer Tablet of Metoclopramide Hydrochloride and Ibuprofen, Bhavesh Shiyani, et. al., AAPS PharmSciTech, Sept. 2008.