Scale up of Semisolid Dosage Forms Manufacturing Based on Process Understanding: from Lab to Industrial Scale
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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.
KEY WORDSquality by design (QbD) design space scale up ointment design of experiments (DoE)
This work was supported by the R&D tax credit of the Ministry of Economic Affairs, The Netherlands (grant number S016053527).
- 1.Levin M. Pharmaceutical process scale-up [Internet]. Marcel Dekker; 2002 [cited 2018 Jan 11]. 566 p. Available from: https://books.google.nl/books/about/Pharmaceutical_Process_Scale_Up.html?id=-HBRzGQRpHkC&redir_esc=y.
- 2.Pandey P, Badawy S. A quality by design approach to scale-up of high-shear wet granulation process. Drug Dev Ind Pharm [Internet]. 2016;42(2):363–9045. Available from: http://www.tandfonline.com/action/journalInformation?journalCode=iddi20%0Awww.tandfonline.com/iddi Google Scholar
- 3.Chang R-K, Raw A, Lionberger R, Yu L. Generic development of topical dermatologic products, part II: quality by design for topical semisolid products. AAPS J [Internet]. 2013 Jul [cited 2014 Aug 20];15(3):674–83. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3691439&tool=pmcentrez&rendertype=abstract.
- 5.van Heugten AJP, Braal CL, Versluijs-Helder M, Vromans H. The influence of cetomacrogol ointment processing on structure: a definitive screening design. Eur J Pharm Sci [Internet] 2017;99:279–284. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0928098716305693
- 8.van Heugten AJP, Versluijs-Helder M, Vromans H. Elucidation of the variability in consistency of pharmacopoeia quality petrolatum. Drug Dev Ind Pharm [Internet] 2017;43(4):595–599. https://doi.org/10.1080/03639045.2016.1274902
- 9.Pandey P, Ewing GD. Rheological characterization of petrolatum using a controlled stress rheometer. Drug Dev Ind Pharm [Internet]. 2008 Feb [cited 2014 Dec 8];34(2):157–63. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18302034