Q&A: Hot-melt extrusion to prepare amorphous solid dispersions: key concepts and common misperceptions

 Dr. Feng Zhang, UT Austin

Please reach out to Dr. Feng at feng.zhang@austin.utexas.edu if you have any further questions.

Q: What should be kept constant in scale up and what must be changed for processing parameters?
A: Depending on what is the limiting factor for the scale up process, generally specific mechanical energy (SME) and residence time distribution (RTD) are kept constant for scale up. Please refer to this book chapters for details. Chen B, Zhu L, Zhang F, Qiu Y*. Developing Solid Oral Dosage Forms. 2nd ed. Qiu Y, Chen Y, Zhang G, Yu L, Mantri RV, editors. Amsterdam: ELSEVIER; 2016. Chapter 31, Process Development and Scale-Up: Twin-Screw Extrusion; p.48. 1176p. (Book chapter)

Q: Process parameters such as screw speed, screw configuration and temperature may have an impact on the actual measured temperature, is there a way to predict the actual temperature and hence better design the experiment?
A: The temperature is mainly controlled by the screw configuration, screw speed and feed rate. Higher temperature is observed with more restrictive screw element, higher screw speed, and lower feed rate. Theoretically, temperature could be predicted if the rheology of the material is known. Practically, there has been a lot of challenges because of the all the physicochemical changes during process.

Q: What are measures about heat sensitive API using twin screw hotmelt extrusion?
A: Higher feed rate and higher screw speed. This would enable the same level of energy input while shortening the residence time. Also, pay more attention to the melt residence time rather than global residence time.

Q: How you can transfer learning on a certain extruder brand to another?
A: I do not have that much experience in that regards since pretty much all my experience is with Leistritz extruder. I would assume certain system parameters such as specific energy input is comparable across different brands for a given formulation.

Q: Why is the temperature after the kneeding zone hotter than the temperature at the kneeding zone?
A: The highest temperature should be right at the end of kneading zone.

Q: Is it true that we should keep same brand for easier scale up?
A: It is true because of the principal of geometrical similarity.

Q: What are the criteria used to determine whether HME, nano wet milling, spray dried dispersion, or other techniques will be used to enhance a given API’s kinetic solubility?
A: Practically, every project starts off with spray drying since API is limited. HME is a much simpler and economical process. Companies often attempt to bridge over to melt extrusion process if there are sufficient materials, time, and budget.

Q: To what extent do you think mechanical breakage of crystalline particles contribute to increasing surface area and solubilization of drug?
A: Not that significant for melt extrusion process unless API has a D50>50 micron.

Q: What is important to control, residence time or input volume to avoid degradation?
A: Higher feed rate and higher screw speed. This would enable the same level of energy input while shortening the residence time. Also, pay more attention to the melt residence time rather than global residence time.

Q: Out of your experience: What is the yield of the small scale extruder when you run it on a minimum amount of material? How much material is lost in the extruder?
A: With Thermo 11 and Leistritz 16 mm extruders, you could process 10 gram and end up with 3-4 gram materials.

Q: Which one (zone temp) affects much to get optimum ASD?
A: Temperature of all zones is important.

Q: What aspects of processing impact the potential for crystallization on storage?
A: Sufficient energy and mixing time are needed to ensure the complete solubilization of crystalline drug in polymer melt.

Q: Could please explain little more about importance of Melt temperature during scale up?
A: It is important to achieve similar temperature profile to ensure the same thermodynamic state of formulations.

Q: Is there any impact of material water content (LoD) on extrude process?
A: Water content can have a HUGE impact on extrusion process. For example, water in copovidone can function as plasticizer. At higher water content, not enough viscous heating is generated, and the melt temperature might be lower. As a result, drug might solubilize in polymer melt.

Q: Is solid dispersion preferred or solid solution?
A: Solid dispersion is more common name.

Q: What variation is there across the length (or relative length) of the kneading elements used in HME? Or is that pretty standard across various systems, and if so, why?
A: Pretty standard. Forward kneading element, 60 or 90 degree, for pharmaceutical system, drug and polymer are pretty miscible.

Q: ASD can help to develop macromolecule at what extent for oral or other route?
A: Macromolecules might not have enough thermal stabilities for them to be melt extruded.

Q: How many products are on the market with HME process?
A: 6-8 products. I am only referring to ASD products here.

Q: In your opinion: Is HME gaining importance in the industry? Or are other methods like spray drying gaining more importance?
A: Both are equally important.

Q: Which polymers are used the most for HME?
A: Copovidone, hypromellose, and hypromellose acetate succinate.

Q: Should the scale up be performed incrementally with screw size or order can be different e.g. 11 mm, 16 mm, 18 mm, 27 mm, 50 mm or can go from 11 mm to any scale based on first principals?
A: Unfortunately, I do not have enough experience to provide a straight answer. My scale up experience is from 18 mm to 27 mm and larger extruder.

Q: When going from 16 mm to 27 mm, what happens to residence time? Does bigger extruders have longer or shorter residence time?
A: In general, residence time can be shortened while maintaining the same quality of extrudate.

Q: I just wonder, in order to ensure similarity in product temperature between lab and production scale extruder, what temperature should be monitors either temperature at die or kneading elements?
A: Both temperature post kneading and at the die is important. Temperature post kneading is important from achieving solubilization of drug in polymer melt perspective. Temperature at the die is important from drug stability perspective.

Q: What roles do melt viscosity and plasticizer play in extrusion temperature?
A: The local heat is controlled by the mixing and melt viscosity. Plasticizer is “never” really used in hot melt extrusion for amorphous solid dispersion. Please note, drugs are plasticizers for polymers in most cases.

Q: What’s typically required in terms of stability of the finished amorphous product? Do the APIs crystallize in vivo upon initial solvation?
A: Drugs need to be chemical (impurity contents are below the limit) and physically (no phase separation or crystallization) stable in finished products during the storage. In most cases, API precipitates as amorphous rather than crystalline particles upon initial solvation.

Q: How critical is polymer selection to get amorphous API by HME which characteristics of polymer need to consider for high melting API?
A: Polymer selection is EXTREMELY crucial. Polymer dictates the drug-polymer phase separation and drug precipitation behaviors that control the drug absorption.

Q: Are there times when you would want to run the conveying element at volume capacity (that is, non-starved)?
A: Only in the case when rely on the screw speed to control the feed rate.

Q: How did you calculate the plots for RTDs? I guess they were based on simulations. Can you please give some insights what methods you used?
A: Please reach out to me directly at feng.zhang@austin.utexas.edu

Q: How can we know if we got a solid dispersion instead of an eutectic mixture?
A: Solid dispersion is consisting of drug and polymer. It is not eutectic mixture.

Q: Is the reference of Dinunzio with thermal imaging also published somewhere? I am curious to learn more. Thermal imaging needs a lot of calibration/reference measurement before one can really trust the data from my experience and I am curious to learn how they mastered the challenge.
A: I do not think the data has been published.

Q: What predictive (modeling) approaches can you suggest to predict HME settings for particular small molecule/polymer combinations?
A: The only commercially available software is Ludovic™. In our experience, their utility is still very limited for pharmaceutical amorphous solid dispersions.

David Preston
David Preston


David Preston has had 38 years of healthcare experience with publicky Traded and Private companies in the fields of Phammaceuticals, Animal Health and Biotechnology as a Board Member. The last 30 years of his xperience has been in China, Taiwan and Hong Kong building successful igh growth businesses. David Has been Chaiman and CEO for Greater China for Sanofi and Boehringer – Ingelheim as well as the Janssen Corporation since 1991 in China. During this time he build high Growth ousinesses in China through diversified strategies in Innovative Pharmaceuticals. branded Generics. Biotechnology. and Animal Healthcare.

Key highlights in this period indluded building of the first Westem Multinational Biotechnoloqy C.M.O. facility as well as obtaining the first Test CM.OJ MAHI license. Establishment of a number of High tech Vaccine Plants, and R and D facilities in in the field of Animal Health. Signing and development of numerous JV’s as well as Wholly owned Subsidiaries. Mergers and Acquisitions across Phamaceutical’s. Animal Health. and Biotechnology industries

David’s achievement’s in the Healthcare industry and it Growth and development in China is widely recognized By the Chinese Govemnment and the City of Shanghai In 2013 he was awarded the Silver Magnolia ollowed in 2015 the Gold Magnolia award. This was then followed by being awarded in 2017 the Honorary Citizen of Shanghai by 40th People’s Municipal Congress of Shanghai. David Holds a Business Science Degree

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Filippo de Vecchi

Director, Advent Partner

Filippo de Vecchi joined Advent in February 2000. He started in the Advent São Paulo office, then moved to Milan in 2002, in 2012 set up the Advent office in Shanghai and in 2016 set up the Hong Kong office. Before joining Advent, he was a senior consultant with Value Partners, in São Paulo and Milan, focusing on strategy and organization in the automotive, energy, cable and media sectors. He began his career at Wasserstein Perella & Co., working as an analyst in the Mergers and Acquisitions department in London and New York. Filippo holds an undergraduate degree cum laude in Economics, with a major in Business Administration, from the LUISS University and an MBA from Columbia Business School, where he currently serves as a member of the Board of Overseers.

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Andrew Li
Andrew Li

Director, Advent Partner

Andrew Li joined Advent in 2012. He previously worked at Warburg Pincus, HSBC PE, Solera Capital and Credit Suisse where he focused on the retail and consumer, healthcare, industrial, and energy sectors. Andrew has worked in finance and private equity throughout the U.S. and China since 1999. Andrew holds a BA from Middlebury College and an MBA from Harvard Business School.    

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Michael Miltenberger
Michael Miltenberger

Director, Advent Partner

Michael Miltenberger  joined Advent in 2011 as an associate on the healthcare team. Following business school, he rejoined Advent’s Boston office, focusing on healthcare investments. Prior to Advent, Michael was a consultant at McKinsey & Company in their Washington DC office, serving a range of healthcare and private equity clients. Michael earned a BA, cum laude, from Harvard College and an MBA from Harvard Business School, graduating with High Distinction as a Baker Scholar and a Harvey Fellow.

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Masood Tayebi
Masood Tayebi, PhD

Director, Operating Partner

Dr. Masood Tayebi is the Founder of BioDuro. He currently serves as CEO of a nationwide real estate portfolio and is a Partner and Chief Executive Officer of the Bridgewest Group. Prior to BioDuro, Dr. Tayebi was Co-Founder and Chairman of Wireless Facilities, Inc. (NASDAQ: WFI), a global leader in telecommunications outsourcing.

  • Co-Founder of Wireless Facilities, Inc.

  • Co-Founder of BioAtla, LLC

  • Recipient of the Ernst and Young 2000 Entrepreneur of the Year award in San Diego

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Kewen Jin
Kewen Jin, PhD

Director, Operating Partner

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Amit patel
Amit Patel

Director, Operating Partner

Amit Patel has twenty years of healthcare industry experience with publicly-traded, private equity-backed, and start-up companies in the capacity of executive, board member, advisor, and investor.  He is currently Executive Chairman of Azurity Pharmaceuticals (a NovaQuest Capital Management portfolio company) and a board member at BioDuro (Advent International portfolio company), Tergus Pharma (Great Point Partners portfolio company) and Calyptus Pharma.  Recently, Amit was SVP & President of Dosage Form Solutions at Capsugel, a KKR portfolio company (purchased from Pfizer in 2011 and sold to Lonza in 2017).   

Prior to Capsugel, he worked at Dr. Reddy’s Laboratories, Inc. as EVP & Head of North America, and SVP & Head of Global Corporate Development & Strategic Planning. Earlier, Amit was VP of Corporate Development at CTIS, Inc., and Co-founder & CEO of MedOnTime, Inc. (acquired by CTIS).  He started his career as a strategy consultant with Marakon Associates. Amit holds an M.B.A. degree from Harvard Business School, a B.S. degree in Economics from the Wharton School of Business, University of Pennsylvania, and a B.A.S. degree in Systems Engineering from the Moore School of Engineering, University of Pennsylvania.

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Haijun Dong
Haijun Dong

Chief Executive Officer

Dr. Haijun Dong currently serves as global CEO of BioDuro-Sundia. He previously was CEO for over 5 years at PharmaBlock Sciences Inc., a public company listed in the Shenzhen Stock Exchange (300725.SZ). The positions he held prior to PharmaBlock includes, among others, Senior Scientist at Boehringer Ingelheim Pharmaceuticals in Ridgefield, Connecticut; Senior Principal Scientist at Roche in Nutley, New Jersey; Head of DMPK and Drug Safety at Roche China R&D Company in Shanghai; Chief Operating Officer of Eli Lilly China R&D Center in Shanghai.

Dr. Dong received his PhD in organic chemistry from the University of Washington in Seattle, Washington, and MBA from China Europe International Business School in Shanghai. 

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Teo Nee Chuan
Teo Nee Chuan

Chief Financial Officer

Teo Nee Chuan joined us in May 2021 as chief financial officer. Prior to joining us, he was chief financial officer of Huazhu Group from November 2015 to May 2021, and was the chief financial officer for Rnomac International Limited, from November 2011 to August 2015. Mr. Teo worked in DDB Greater China Group, was appointed as the chief financial officer in September 2009, and was additionally appointed as the director of operations in January 2011. He previously served in Focus Media Group and was appointed as the financial deputy director in June 2007. Prior to that, from September 1994 to May 2007, Mr. Teo worked at Ernst & Young and Ernst & Young Business Services Ltd. in various positions in Kuala Lumpur and Toronto, including as a senior manager in the Transaction Advisory Services. Mr. Teo has been an independent director of 111, Inc. (a company listed on the NASDAQ, ticker symbol: YI) since September 2018. Mr. Teo received his Bachelor of Science in Accounting and Financial Analysis degree from The University of Warwick in the United Kingdom in July 1994. He is a Chartered Certified Accountant in the United Kingdom, who has obtained his qualification in July 1998 from The Association of Chartered Certified Accountants, and is a Certified Public Accountant in the United States and Hong Kong, who has obtained his qualification from American Institute of Certified Public Accountants in May 2002 and Hong Kong Society of Accountants in October 2003, respectively.

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TJ Deng, PhD

President, Discovery

Dr TJ Deng joined BioDuro in the initial stages of the company and helped BioDuro grow to an industry leading discovery services organization. He established and managed several scientific departments, including DMPK, before transitioning to a leader of the business and operations functions. Prior to joining BioDuro, Dr. Deng spent six years at PPD, in positions with increasing responsibilities from scientist to scientific manager.




  • Developed the extractable/leachable capabilities at PPD
  • 18 years industry experience

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Kent Payne
Kent M. Payne, PhD

Chief Executive Officer

Kent is distinguished as a business operator and leader in areas of sales, commercial manufacturing and product development. He has extensive executive experience in M&A as well as successfully running, start up, growth and turn around businesses. This includes both Fortune 500 and Private Equity environments. He combines strong business leadership, successful P&L track record, and technical background to strategically lead and grow enterprise value across Biotechnology and Pharmaceutical market segments. He has successfully led the geographic expansion of businesses into Europe, Asia, and South America in addition to the United States.  He currently serves as CEO for BioDuro-Sundia, LLC (an Advent International company). He also currently serves as a board member for Goodwin Biotechnologies (a Signet Healthcare company). 

Prior Roles

  • President, Global CMC Solutions BioDuro-Sundia, a global
  • CEO Socorro Pharmaceuticals, LLC, a generic pharmaceutical
  • President Americas, Qualicaps Inc.(a Mitsubishi Chemical Holdings subsidiary)
  • Principal Consultant and Partner at CoreFactor LLC, providing executive strategic, licensing and operational advisory services to clients.
  • Vice President/General Manager Catalent Pharma Solutions, Inc. (a Blackstone Group company formed in 2007, formerly part of Cardinal Health)
  • Progressive leadership responsibility at: Novartis, Monsanto and G.D. Searle.  

Prior Brand Position

  • Board Advisor Vitruvias Therapeutics
  • Board Member Qualicaps, Inc. (a wholly owned subsidiary of
    Mitsubishi Chemical Holdings)
  • Board member Technophar, Inc. (a wholly owned subsidiary of
    Mitsubishi Chemical Holdings)
  • Board Advisor, Corporate Strategy Office, Life Science Institute
    Inc. (a wholly owned subsidiary of Mitsubishi Chemical Holdings)
  • Non-executive Chair and Board Member PDS Biotechnology·        (PDSB: NASDAQ)

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John Phillips
John Phillips

Vice President, Business Development (US & EU)

Coming soon…



  • Coming soon…

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Roy Xu
Roy Xu

Chief Strategy Officer

Roy has over 25 years of healthcare industry experience.  He started his career as an orthopedic surgeon.  Roy joined Eli Lilly as a sales rep in 1997.  Since then he has had various roles in market research, business intelligence, BU head, strategy, regional general management, business development etc., both at Eli Lilly and Boehringer Ingelheim (BI).  Roy also spent more than two years in Germany where he was BI’s Director of Corporate Business and Enabling Strategy.

Roy obtained a bachelor’s degree in Clinical Medicine at Zhejiang Traditional Chinese Medicine University, and an MBA from Zhejiang University.



  • 25 years of healthcare industry experience including Eli Lily and Boehringer Ingelheim. 
  • Former Director of Corporate Business & Enabling Strategy at oehringer Ingelheim in Germany.

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San Diego

San Diego - BioDuro-Sundia

Our San Diego site is our corporate headquarters. The facility is home to BioDuro-Sundia’s drug product development technologies and has 9 GMP clean rooms. Development and manufacturing operations are conducted for projects up to Phase III clinical trials.

Size: 44,000 sq. ft.
Featured capabilites: Tableting, Coating, Hot Melt Extrusion, Spray Dried Dispersion

11011 Torreyana Rd.
San Diego
CA 92121
United States

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BioDuro Beijing

Operating since 2006, our Beijing site is home to BioDuro-Sundia’s first wet chemistry operations. With 300 regular fume hoods and 18 scale-up chemistry hoods the Beijing facility houses most of BioDuro’s chemistry operations, while also hosting labs for biology and monoclonal antibody discovery.

Size: 100,000 sq. ft. 
Featured capabilities: Radioactivity Lab, Monoclonal Antibody Discovery, Medicinal Chemistry

No. 29 Life Science Park Road
Changping District Beijing,
P.R. China

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BioDuro- Shanghai Facility

Established in 2012, BioDuro-Sundia’s Shanghai facility has been growing with its departments. The cutting edge facility contains labs for ADME, bioanalysis, in vitro assays and translational research. The site includes a 18,000 sq. ft vivarium and 20,000 sq. ft of office space.

Size: 92,000 sq. ft.
Featured capabilities: Scale-up Chemistry, Discovery Biology, DMPK, In Vivo Pharmacology

No. 233 North Fu Te Road
Waigaoqiao Free Trade Zone
Shanghai, 200131
P.R. China

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Cathy Yen
Cathy Yen

Director, Operating Partner

Cathy joined the Board of Directors of BioDuro-Sundia in 2020, with the Advent-led acquisition of Sundia and creation of BioDuro-Sundia. Prior to that, she was Chairman of the Board at Sundia Meditech Group, where she was the key architect of Sundia’s strategic vision and growth. Under her leadership, Sundia solidified its position as one of the leading pre-clinical CROs in China.

Prior to Sundia, Cathy had a distinguished career as a seasoned venture capitalist, having led numerous investments in high-growth companies in Asia. Cathy served as a Partner of AsiaVest Partners, TCW/YFY Ltd., a global venture capital firm, for over a decade, Vice President at Global Financial Services, Vice President at Crimson Ventures/Chinatrust Bank and Senior Manager at Fortune Capital. She brings over 20 years of experience in corporate finance, accounting, strategic planning and private equity investments. 

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Wuxi - BioDuro

Established in 2019, BioDuro-Sundia’s fully integrated discovery facility located at the heart of Jiangsu Wuxi Life Science & Technology Industrial Park with plans of growing staff to 1000+ scientists.

Size: 300,000 sq. ft.
Featured capabilities:
Discovery Chemistry & Biologics, Biology, DMPK, Pharmacology, CMC Services

no.1699,Huishan avenue
Huishan Economic 
Development Zone,Wuxi
P.R. China

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Hebei - Sundia

Established in 2011, this pilot plant this handles mg to kg scale up.

Size: 45,208 sq. ft.

Featured capabilities: SFFS Chemistry: mg to kg scale up
(150 hood)

238 Changjiang Road
Hebei province
P.R. China

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