Review of Trends in Oral Solid Dosage Manufacturing

The state of solid oral dose manufacturing is influenced by new approaches, new technologies and structural changes in the raw material market.

When you think of medicine, the first image that comes to mind will probably be a little white pill, or maybe an orange bottle full of pills. While biological and various parenteral therapies have seen significant advances in recent years, the ubiquity of oral solid dosage (OSD) drugs – whether pills, tablets, capsules, capsules, effervescence, gummies or any other variation – remains at the forefront of the industry.

“OSD drug delivery systems are primarily preferred over intravenous parenteral (injection or drip) drug delivery for many reasons,” said Paul DiMarco, vice president of global business operations, BioSpectra. “Including ease of use, lower purity requirements due to the acidic environment of the stomach, and little or no medical supervision during administration.

OSD’s popularity places it at the heart of the pharmaceutical industry, and it is particularly sensitive to emerging trends or market forces. This article examines the latest technologies and trends unique to OSD, as well as an overview of the market forces influencing its production.

Adopt new approaches

One process that the pharmaceutical industry as a whole has attempted to adopt, where possible, is continuous manufacturing, due to the decreased resource depletion and increased flexibility that continuous processes provide. However, while continuous manufacturing has seen steady growth, OSD has encountered challenges in moving forward due to the nature of its manufacturing process – the first oral solid dosage drug manufactured via a continuous approach has not been approved only in 2015 (1). In large part, these difficulties resulted from the fact that the equipment was designed with downtime in mind.

In this regard, various equipment vendors have stepped in to try to alleviate the ongoing manufacturing issues. For example, LB Bohle’s QbCon1, a continuous dryer and granulator, uses a new process to allow infinite operation without the need to stop the machine for cleaning (2). Similarly, Herma US has launched modules for its 132M HC wrap-around labeler that allow it to be integrated into a continuous manufacturing process without requiring downtime for replacement paper (3). Along these lines, companies have realized that facilities must be designed with continuous “powder to tablet” capabilities in mind.

On the customer side, there has also been increased demand for other new approaches, as Robert Sedlock, director of Natoli Scientific, notes.

“In recent years, there has been a push for data collection in a more scientific approach. USP [United States Pharmacopeia] published a new chapter (4) regarding tablet characterization methods, which require instrumented tablet presses,” says Sedlock. “There is now an increased demand for instrumented single-station machines, rotary tablet presses and compaction emulators/simulators. Understanding the mechanical properties of materials is now a standard in the OSD industry.

This standard is a natural evolution of today’s pharmaceutical industry: as data integration becomes more pronounced, client companies are going to want more detailed information to refine their processes. Savvy manufacturers will build and design processes with this in mind to meet ever-increasing data demands, which in turn will continually influence OSD manufacturing technologies and approaches.

Materials Sourcing Review

A striking dichotomy has emerged in the supply of the two components of oral solid dosage drugs, excipients and APIs. Excipients are generally considered more complex than APIs, largely due to their multi-component nature. This characteristic often results in a poor understanding of the impact on the performance of the various components; similarly, the compositional profiles of complex mixtures may not be well defined. In contrast, APIs are relatively simple mixtures – they are enhanced by reducing the presence of all other chemicals, which can render them inert or lead to unintended side effects (5).

However, the large difference in relative complexity has determined who produces them. Since excipients are relatively complex formulations, they require significant regulatory oversight to ensure consumer safety. Therefore, they are largely manufactured in countries with well-regarded global regulations; North America holds the largest share of the pharmaceutical excipients market, followed by Europe (6).

“Pharmaceutical companies in the United States and Europe are held to a legitimate standard by [FDA]– a situation that is not equally experienced by their counterparts in China and India,” says DiMarco. “These companies use higher purity ingredients and fine chemicals from local manufacturers and therefore produce higher quality products. [and] more consistent and sophisticated finished pharmaceutical products.

APIs, on the other hand, do not need to be scrutinized, allowing countries like India and China, which have less stringent regulations and much lower labor costs , to take advantage of these characteristics to take control of manufacturing. While it should be noted that there is some disagreement over the precise numbers, particularly because most drugmakers do not need to disclose where they source their APIs, in 2017, the Medicines and Healthcare UK products Regulatory Agency (MHRA) estimated that 40% of global API production came from China at the time of the report (7). Similarly, a 2021 report by Mordor Intelligence, a marketing intelligence firm, indicated that approximately 75-80% of APIs imported into the United States originated from China or India at the time of their report (8).

This dichotomy in material sourcing has shaped the landscape of the oral solid dose manufacturing industry. For example, while there have been calls to relocate production following supply chain disruptions caused by the COVID-19 pandemic, the United States’ reliance on these countries for API provisioning complicates this issue; it is particularly exacerbated by the desire to reduce drug costs, which necessitates outsourcing to countries that can set prices according to their labor costs.

“Supply chain security issues that began with the China-US tariff wars, followed by the pandemic, continue today with strained supply chain logistics and constraints raw material capacity,” DiMarco said. “The deterioration of the relationship between the United States and China could quickly lead to a more serious conflict and could easily become an existential event that would overshadow all previous challenges regarding supply chain issues and constraints.”

References

1. Vertex Pharmaceuticals, “FDA Approves Orkambi,” press release, July 2, 2015.

2. LB Bohle, “Continuous Granulation and Drying for the Pharmaceutical Industry QbCon 1 – R&D,” www.lbbohle.comaccessed 28 October 2022.

3. Freudenberg Medical, “Freudenberg Medical Launches HeliFlex TPE Tubing at International Bioprocess Conference,” press release, September 29, 2022.

4. USP, “General Chapter Characterization of tablet compression”, USP 36–NF 31 (Rockville, MD, December 1, 2017).

5. B.Carlin, et al., Pharmaceutical technology 46 (8) 2022.

6. IPEC Federation, Qualification of excipients for use in pharmaceuticals (IPEC, Brussels, 2nd ed., 2020).

7. MHRA, Medicines and Healthcare Products Regulatory Agency International Strategy, www.gov.uk (2017).

8. Intelligence of Mordor, Active Pharmaceutical Ingredients (APIs) Market Growth, Trends, COVID-19, and Forecast, (2022-2027)Market research report, 2021.

About the Author

Grant Player is the associate editor of Pharmaceutical technology, BioPharm International, and Pharmaceutical Technology Europe.

Item details

Pharmaceutical technology
Flight. 46, No. 10
October 2022
Pages: 26-27

Quote

When referencing this article, please cite it as G. Playter, “Examining Trends in Oral Solid Dosage Manufacturing,” Pharmaceutical technology 46 (11) 26-27 (2022).

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