Title : Preparation and Characterization of Gliclazide Nanosuspension

Authors : Mohammad Shariare, Tabassum, Nabilah, Zaman, Shamita, Sabbi, Safayar, Kalam, Natasha, Reza, Hasan Mahmud

Abstract : Purpose Gliclazide, which belongs to the BCS class II drugs, exhibits low solubility and high permeability characteristics. There are a number of formulation approaches to improve the solubility of this group of drugs one of which is the formulation of nanosuspensions. The aim of this study was to prepare gliclazide nanosuspension as a model drug using antisolvent precipitation method to improve the dissolution profile. Methods Different batches of nanosuspension were prepared by antisolvent precipitation method. In this study acetonitrile is used as a solvent and water as an antisolvent. Various stabilizers such as - Hydroxy Propyl Methyl Cellulose (HPMC), Polyethylene glycol (PEG) 6000, Polyethylene glycol (PEG) 4000, Poloxamer 188 and their combinations were used following a full factorial experimental design where three process parameters ( stirring rate, stirring time, rate of antisolvent addition) were used at two levels (H= high; L=low). The nanosuspension batches were characterized using inverted phase microscope, scanning electron microscopy (SEM) and Malvern Zetasizer Nano Zs90 to obtain particle size, size distribution and Zeta potential value. For dissolution study USP apparatus 2 was used using phosphate buffer pH 7.4 at 100 rpm. Results Results showed that nanosized gliclazide particles were observed in the range of 180-510 nm when characterized using Inverted phase microscopy and Scanning Electron Microscopy (SEM). These results are further supported by the particle size distribution data obtained using Malvern zetasizer (Figure 1a). Nanosuspension batch processed using all high parameters exhibit smallest average particle size (186 nm ± 56) with a zeta potential value of -24.05 mV (Figure 1b) which indicates that the nanosuspension batch is relatively stable. This is probably due to higher stirring and addition rate of antisolvent leading to small sized gliclazide particles. It was observed that nanosuspension batches with a longer stirring time (30 minutes) produced smaller drug particles (243 nm ± 21) compared to less stirring time (15 minutes) (321 nm ± 43). High rate of addition of drug solution (2ml/sec) into antisolvent leads to small particle size (298 nm ± 42) compared to low addition (1ml/sec.) rate (445 nm ± 38), since the mixing efficiency is enhanced which slows the crystal growth process resulting in small sized particles. Higher stirring rate gives a lower average particle size (186 nm ± 56) compared to low stirring rate (507nm ±80). This may be due to the increased efficiency of mixing between the multiphases which generates a high level of supersaturation. Gliclazide nanosuspension showed a rapid dissolution rate compared to raw gliclazide powder. For the raw material, only 40% of the drug was dissolved while for nanosuspension batches 100% drug was dissolved after 30 mintues. Conclusion This study demonstrates that antisolvent precipitation method represents an effective approach for preparing gliclazide nanosuspension. However processing conditions showed to have marked impact on particle size of nanosuspension batches. Gliclazide exhibited faster dissolution rate when formulated as nanosuspension

Journal : Volume : Year : 2015 Issue :
Pages : City : Orlando, Florida Edition : Editors :
Publisher : AAPS annual meeting and exposition , 2015 ISBN : Book : Chapter :
Proceeding Title : American Association of Pharmaceutical scientists (AAPS) Annual Meeting and Exposition, USA Institution : Issuer : Number :