Title : Formulation and Optimization of Epigallocatechin Gallate (EGCG) Nano Drug Delivery System Using QbD Approach

Authors : K. Afnan, S. B. Haque, T. Tasnim, M. Kazi, H. M. Reza, M. H. Shariare

Abstract : Purpose Epigallocatechin-3-gallate (EGCG), a principal polyphenol and active component of green tea, which exhibits a variety of biological and medicinal benedictions. However, they exhibit low bioavailability and are poorly absorbed across the GIT. To overcome this limitation, we aimed to formulate catechin loaded nano phytosomes, newly acquainted forms of herbal formulations, with better bioavailability, entrapment efficiency, and stability using quality by design approach. Methods Catechins were extracted from green tea leaves using water as a solvent at the different temperature. The content of EGCG in the extracted catechins was determined using ultra-performance liquid chromatography (UPLC). The effects of key material attributes (concentration of drug, concentration of phospholipid and concentration of cholesterol, and PH of buffer solution) and process parameters (addition rate, stirring time, stirring speed and temperature) were investigated using a full factorial design at two levels (H= high; L=low)(Table1). The mean particle diameter, polydispersity index (PDI) and % drug encapsulation efficiency were considered as critical quality attributes (CQA). Minitab Statistical Software was employed to evaluate the impact of each variable on the quality attributes of phytosome. Nano phytosomal batches were characterized using Malvern Zetasizer, Scanning Electron Microscopy, and Inverted phase microscopy. Results The result obtained from UPLC, showed that 500?g EGCG was present in per ml of green tea extract. Particle size distribution data showed that phytosomes were in the range of 130-270 nm, when characterized using Malvern Zetasizer and microscopic method. Addition rate and concentration of phospholipid were identified as critical process parameters (CPP) and critical material attributes (CMA) respectively, affecting the quality attributes of phytosome. Phytosome batches which proceeded at high addition rate exhibited smaller particle size (134.6±8.7 nm) and PDI (0.241±0.008) compared to the batches proceeded at low addition rate (160±12.5 nm). This is probably due to the enhancement in mixing efficiency, which slows the crystal growth process resulting in small sized particles. Phospholipid concentration did not have any impact on the average particle size of phytosome when buffer pH was 5.5, while at pH 7.0 increased concentration of phospholipid led to a small average particle size of phytosome. Entrapment efficiencies for phytosome batches were in the range of 63.29% to 86.68%, which was related to the size of the phytosomes. Conclusion This study suggests that the phospholipid concentration and addition rate have marked impact on average particle size, PDI and encapsulation efficiency of Nano phytosomes. Critical processing conditions and material attributes were identified through a designed study based on the philosophy of QbD

Journal : Volume : Year : 2016 Issue :
Pages : City : Denver, Colorado, USA Edition : Editors :
Publisher : AAPS annual meeting and exposition , 2016 ISBN : Book : Chapter :
Proceeding Title : American Association of Pharmaceutical scientists (AAPS) Annual Meeting and Exposition, USA. Institution : Issuer : Number :