AAPS PharmSciTech

, Volume 19, Issue 5, pp 2330–2334 | Cite as

Scale up of Semisolid Dosage Forms Manufacturing Based on Process Understanding: from Lab to Industrial Scale

  • Anton J. P. van HeugtenEmail author
  • Herman Vromans
Research Article


The scale up of production processes is a major challenge in pharmaceutical industry. Using a quality by design approach, upscaling can be based on the design space, which can be assessed on a small scale. In a previous study, the critical process parameters were identified by a definitive screening design on cetomacrogol ointment. In the current study, this lab scale (0.5 kg) study was scaled up to industrial scale (2000 kg, filling 100g tubes at 75 tubes/min). A similar trend for the influence of filling temperature on ointment yield stress was found for lab and industrial scale production. Furthermore, a process window for ointment filling viscosities was established. It was shown that between 26 and 170 Pa.s ointment could be filled into tubes with a low weight variation (< 0.5% RSD) resulting in a product with a yield stress that meets the pre-set criteria. This approach was subsequently verified using several creams and ointments and showed general applicability.


quality by design (QbD) design space scale up ointment design of experiments (DoE) 


Funding Information

This work was supported by the R&D tax credit of the Ministry of Economic Affairs, The Netherlands (grant number S016053527).


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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  1. 1.Department of Pharmaceutics, Utrecht Institute for Pharmaceutical SciencesUtrecht UniversityUtrechtThe Netherlands
  2. 2.Research and Development Department, Tiofarma B.VOud-BeijerlandThe Netherlands
  3. 3.Department of Clinical Pharmacy, Division of Laboratory Medicine & PharmacyUniversity Medical Centre UtrechtUtrechtThe Netherlands

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