Maria L.A.D. Lestari, Rainer H. Müller and Jan P. Möschwitzer * Pages 147 - 161 ( 15 )
Background: Miniaturization of nanosuspensions preparation is a necessity in order to enable proper formulation screening before nanosizing can be performed at large scale. Ideally, the information generated at small scale is predictive for the large scale production.Objective: This study was aimed to investigate the scalability when producing nanosuspensions starting from a 10 g scale of nanosuspension using low energy wet ball milling up to production scales of 120 g nanosuspension and 2 kg nanosuspension by using a standard high energy wet ball milling operated in batch mode or recirculation mode, respectively. Method: Two different active pharmaceutical ingredients, i.e. curcumin and hesperetin, have been used in this study. The investigated factors include the milling time, milling speed, and the type of mill. Results: Comparable particle sizes of about 151 nm to 190 nm have been obtained for both active pharmaceutical ingredients at the same milling time and milling speed when the drugs were processed at 10 g using low energy wet ball milling or 120 g using high energy wet ball milling in batch mode, respectively. However, an adjustment of the milling speed was needed for the 2 kg scale produced using high energy wet ball milling in recirculation mode to obtain particle sizes comparable to the small scale process. Conclusion: These results demonstrate confirm in general the scalability of wet ball milling as well as the suitability of small scale processing in order to correctly identify the most suitable formulations for large scale production using high energy milling.
High energy wet ball milling, low energy wet ball milling, nanosuspension, scalability, screening, wet ball milling.
Department of Pharmaceutics, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Department of Pharmaceutics, Biopharmaceutics & NutriCosmetics, Institute of Pharmacy, Freie Universität, Berlin, Department of Pharmaceutics, Biopharmaceutics & NutriCosmetics, Institute of Pharmacy, Freie Universität, Berlin