TY - JOUR
T1 - Medium and large scale preparation of Nanostructured Lipid Carriers of asenapine maleate
T2 - Quality-by-design based optimization, production, characterization and performance evaluation
AU - Rao, Rajat Radhakrishna
AU - Pisay, Muralidhar
AU - Kumar, Sunil
AU - Kulkarni, Sanjay
AU - Pandey, Abhijeet
AU - Kulkarni, Vijay Induvadan
AU - Mutalik, Srinivas
N1 - Funding Information:
The authors are thankful to the Biotechnology Industry Research Assistance Council (BIRAC), Department of Biotechnology , Government of India, New Delhi for financial support (BT/AIR0404/PACE-14/18). The authors are also thankful to MSN Organics Pvt Ltd, (Hyderabad, India) for providing a gift sample of the asenapine maleate. The authors are grateful to i) SteerLife, Bangalore for providing Senior Research Fellowship to Mr Rajat R Rao and to ii) Manipal Academy of Higher Education (MAHE), Manipal for providing Dr T M A Pai Doctoral Fellowship to Muralidhar Pisay and Sanjay Kulkarni.
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/5
Y1 - 2022/5
N2 - In the present study, scale-up of preparation of Asenapine maleate (ASPM) loaded Nanostructured lipid carriers (NLCs) to medium as well as the large scale was performed with the aid of Quality-by-Design (QbD) approach. High-pressure homogenization (HPH) was used to scale up the ASPM loaded NLCs to medium (40 mL) and large-scale (300 mL) batches. The statistical experimental design was employed to optimize the HPH parameters and the results of the design showed that the size of ASPM loaded NLCs decreased with the increase in pressure and number of cycles of HPH. Also, increasing the number of cycles resulted in a slight increase in the %drug entrapped. FTIR and DSC were used to assess the compatibility between drug and excipients. The shape and surface morphology of NLCs studied by Transmission Electron Microscope revealed a spherical shape with an approximate size of less than 100 nm. The cytotoxicity of NLCs using MTT assay in Caco2 cells demonstrated the safety of ASPM-NLCs. Further, in vivo pharmacokinetics and efficacy studies strengthened the applicability of ASPM-NLCs produced at a large scale for further in vivo and clinical environments.
AB - In the present study, scale-up of preparation of Asenapine maleate (ASPM) loaded Nanostructured lipid carriers (NLCs) to medium as well as the large scale was performed with the aid of Quality-by-Design (QbD) approach. High-pressure homogenization (HPH) was used to scale up the ASPM loaded NLCs to medium (40 mL) and large-scale (300 mL) batches. The statistical experimental design was employed to optimize the HPH parameters and the results of the design showed that the size of ASPM loaded NLCs decreased with the increase in pressure and number of cycles of HPH. Also, increasing the number of cycles resulted in a slight increase in the %drug entrapped. FTIR and DSC were used to assess the compatibility between drug and excipients. The shape and surface morphology of NLCs studied by Transmission Electron Microscope revealed a spherical shape with an approximate size of less than 100 nm. The cytotoxicity of NLCs using MTT assay in Caco2 cells demonstrated the safety of ASPM-NLCs. Further, in vivo pharmacokinetics and efficacy studies strengthened the applicability of ASPM-NLCs produced at a large scale for further in vivo and clinical environments.
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U2 - 10.1016/j.jddst.2022.103275
DO - 10.1016/j.jddst.2022.103275
M3 - Article
AN - SCOPUS:85127248333
SN - 1773-2247
VL - 71
JO - Journal of Drug Delivery Science and Technology
JF - Journal of Drug Delivery Science and Technology
M1 - 103275
ER -