Title : The Impact of Different Stabilizers in the Preparation and Development of Nanosuspension for Different Drugs

Authors : T. S. Mimi, N. J. K. Pinky, S. R. Santa, H. M. Reza, M. Kazi, M. H. Shariare

Abstract : Purpose: Poor solubility and poor bioavailability are major hurdles for BCS classes II and IV group of drugs. To overcome this obstacle, we used the antisolvent precipitation method to prepare nanosuspensions. Nanosuspensions of four different drugs were prepared using four different stabilizers, in order to evaluate stabilizers relative affinity towards different drugs, and its impact on average particle size. Methods: Nanosuspensions of BCS class II and IV drugs were prepared using acetone and acetonitrile initially as a solvent, and water as an antisolvent. The four different stabilizers used were SLS, HPMC, Pluronic 407, PEG 4000. BCS class II drugs used in this study are Gliclazide, Alprazolam, Clonazepam, and Nitazoxanide was the BCS class IV drug. Nanosuspension batches were characterized using Malvern Zetasizer in order to determine particle size, PDI, and zeta potential values. Results: Malvern Zetasizer data suggests that the average particle size of nanosuspensions were in the range of 100-1400 nm. Results indicate that injection rate, and solvent used are the critical factors that affect the average particle size in the preparation of nanosuspensions of different drugs. It was observed that low average particle size (111.9 nm) is obtained from the solvent in which drugs are sparingly soluble (acetone) (Figure 1). High injection rate (1 ml/sec) resulted in smaller particle size (111.9 ± 1.02 nm) compared to low injection rate (0.5 ml/sec) (664.9 ± 36.8nm). The impact of four different stabilizers on four different drugs was observed, with respect to their average particle size (Figure 2). Nanosuspension batches prepared using P407 showed smallest particle size for gliclazide, alprazolam, and nitazoxanide compared to other stabilizers. For clonazepam both SLS and Pluronic 407 showed low average particle size (Table 1). This may be attributed to the relative affinity and solid surface chemistry between drug and stabilizer molecule. According to the zeta potential values, nanosuspension batches prepared using HPMC and SLS showed high value for all four drugs. Conclusion: In this study the critical factors identified were solvent used, injection rate, and type of stabilizer. Sparingly soluble solvent and high injection rate resulted in small average particle size. Pluronic 407 was found to be the stabilizer of choice for most of the drugs.

Journal : Volume : Year : 2018 Issue :
Pages : City : Washington DC Edition : Editors :
Publisher : AAPS annual meeting and exposition , 2018 ISBN : Book : Chapter :
Proceeding Title : American Association of Pharmaceutical scientists (AAPS) Annual Meeting and Exposition, USA. Institution : Issuer : Number :