In the fast growing API and excipient markets, solubility, taste-masking and functionality are the focus. Susan Birks looks at current trends and issues on the horizon
Kollicoat Smartseal 30 D from BASF is an aqueous dispersion of a film forming polymer for taste masking and moisture barrier applications
Despite Big Pharma’s current doldrums, the markets for active pharmaceutical ingredients (APIs) and excipients are growing at a healthy rate. According to the most recent report by RNCOS analysts, the global market stood at US$113bn in 2012 and was forecast to grow at a CAGR of around 8% in the period 2012–2017.1 The US market accounts for the majority of this, while it is estimated that the European market will reach around $38.3bn by 2017.2 Demand behind this growth stems from the continued rise in the biotech and generic sectors, according to Transparency Market Research.3 However, increased market fragmentation and reduction in Big Pharma’s overall R&D expenses are some of the factors that could hamper the future growth of the market.
It is a similar story for pharmaceutical excipients, as the market for fillers, binders, lubricants and preservatives is poised to reach $7.3bn by 2018.4 The market was valued at $5.7bn in 2013 and is expected to see continued growth from 2013–2018. The increasing use of generics is also boosting the main categories of excipients, including carbohydrates, oleochemicals, petrochemicals, polymers, microcrystalline cellulose, sugar and calcium carbonate.
Completely new excipients are few and far between but more sustainable sources, improved methods of production and increased functionality are factors helping to propel the growth of this market. Many traditional excipients are increasingly being marketed as functional ingredients, while more combination excipients are also being offered, as they can provide functionality improvements without having to go through the same regulatory hurdles as new excipients.
North America currently accounts for around 33–34% of the global pharmaceutical excipients market, closely followed by Europe. Major players in this market include Ashland, BASF, Dow Chemical Company, Roquette, FMC Corporation, Evonik, ADM, Lubrizol and Croda, JRS Pharma and Associated British Foods (ABF). In an effort to stave off competition from countries such as China and India, the US and Western suppliers continue in their quest to offer superior quality products and to ensure greater supply chain security.
Excipient manufacturers are applying various novel technologies to reduce processing time and the market has witnessed a shift towards the use of co-processed excipients and the direct compression method of producing tablets. Dow’s Methocel DC2, for example, is a material that has been designed to reduce manufacturing costs by improving processability in dry powders and enabling the switch from batch wet granulation techniques to continuous dry processing techniques, such as roller compaction or direct compression.
Dow has responded to demand for enhanced solubility with its Affinisol platform, which can make spray-dried or hot melt extruded ingredients more soluble
According to Dow’s Global Strategic Marketing Leader, Dago Caceres, solubility enhancement is still the number one issue for drug manufacturers. Dow has responded with its Affinisol platform, to help solve the insoluble in spray-dried dispersions and hot melt extrusion (HME) formulations. Its Affinisol HPMCAS, for example, facilitates higher solids content in solution for higher throughput in spray-drying while maintaining solubility enhancement. Affinisol HPMC, meanwhile, is a hypromellose polymer with improved thermal properties designed for HME formulations. It can be extruded over a wide temperature range without need of plasticisers, which widens the processing window and improves product throughput.
Similarly, Ashland is marketing AquaSolve HPMCAS. Initially developed for enteric film coatings to provide gastric resistance, more recently it has been offered as an excipient for improving the solubility of APIs for solid solutions prepared by HME and spray drying. ‘AquaSolve HPMCAS represents the latest advancement in solubilisation solutions from Ashland,’ says John Carney, Global Sales Director, of its pharmaceutical specialities. ‘Going forward, we will be developing new products to meet our customers’ evolving needs, such as tailored molecules ideally suited to specific candidate APIs.’
Excipients that specifically address the issues of medicines for young and old patients are in demand
Excipients that specifically address the issues of medicines for young and old patients are also in demand. Dow’s ion exchange resins have taste-masking properties that can be employed in products such as syrups. Meanwhile Roquette is marketing Kleptose Linecaps 17, whose flexible amylose helix combines easily with APIs and is useful for taste-masking and encapsulation of apolar molecules. Also in the area of palatability, SPI Pharma has introduced Actimask Ibuprofen 92S, a taste-masked ibuprofen that joins Actimask Acetaminophen 92M in SPI’s line of taste-masked actives for patient-friendly orally dispersible dosage forms made on conventional equipment.
Other trends in dosage forms, such as capsules, were highlighted at CPhI by Heiner Hoppmann, CEO of the Aenova Group, which supplies packaging for solid dosage forms, including soft and hard capsules and tablets. Hoppmann said there was a continued shift away from animal products, but whereas this was started by fears of Bovine spongiform encephalopathy (BSE) over a decade ago, today the move was more for religious and ethical reasons.
Besides the structural market drivers, there are strong geographic drivers for the growth of the pharmaceutical excipients market. The economic situation and cost-containment issues have diverted excipient manufacturers from the North American and European regions to emerging markets such as India, China and Brazil. Some major companies are establishing subsidiaries in these regions. Developing countries such as India and China have a relatively high CAGR rate and are expected to see significant market growth due to low labour costs and the rising demand for healthcare.5 However, a backlash against product adulteration and quality issues has also seen some Western companies pull out of the region and Western regulatory authorities are placing greater scrutiny on imported ingredients and on the supply chain.
To help companies cope with the increasing regulatory burden of tracking and certifying ingredients, Merck Millipore has launched an online tool for tracking the original manufacturer of nearly 4,000 of its materials, including excipients, biopharm ingredients and APIs. The company says its electronic Original Manufacturer Tracking (eOMT) saves users time in research and enables compliance with regulatory requirements. Prior to availability of the eOMT tool, the original manufacturer had to be researched manually via a lengthy process. The eOMT tool fulfills the FDA requirement that the original manufacturer should be disclosed in the Certificate of Analysis (COA) or separately in another document. The tool also helps users meet EXCiPACT guidelines, an industry-driven certification scheme for excipients.
Business confidence in the chemical and pharmaceutical sector is generally optimistic, but energy costs are a growing concern
European suppliers, meanwhile, face other challenges. A recent survey of UK manufacturers by the UK Chemical Industry Association (CIA) suggested business confidence in the chemical and pharmaceutical sector was generally optimistic, but energy costs were a growing concern. Energy prices have risen steeply in countries such as the UK and Germany, which are looking to promote more sustainable renewable energy sources. Adrian Hanrahan, MD of speciality chemicals manufacturer Robinson Brothers, which supplies the industry with fine chemicals and intermediates, highlighted the issue at CPhI when he said that in 2013, his company had ‘reduced energy by 30% per tonne but energy costs had risen by 45%.’
Steve Elliott, Chief Executive of the CIA, urged the UK Government to take action in a recent statement, warning that: ‘Without urgent action on energy costs, where UK businesses face a huge price differential opposite their US competitors, and the European regulatory framework – still far too restrictive in terms of investment, jobs and growth – I fear the general optimistic outlook of our members will fade’.
1. Global API Market Forecast to 2017 from www.reportlinker.com
2. Active Pharmaceutical Ingredients (API) Market in Europe to 2017, from marketresearchreports.biz