Acta Pharm. 65 (2015) 133-146

 

full paper

Original research paper

 

Clozapine-carboxylic acid plasticized co-amorphous dispersions: Preparation, characterization and solution stability evaluation

AHMED MAHMOUD ABDELHALEEM ALI, ADEL AHMED ALI and IBRAHIM ABDULLAH MAGHRABI

ahmed.abdelhalem@pharm.bsu.edu.eg or ahmed.mahmoud3@yahoo.com

1 Department of pharmaceutics, Faculty of Pharmacy, Beni Suef University, Egypt

2 Department of clinical pharmacy, Faculty of Pharmacy, Taif University, Kingdom Saudi Arabia

Accepted Novembe 3, 2014

 

This study addressed the possibility of formating of co-amorphous systems between clozapine (CZ) and various carboxylic acid plasticizers (CAPs). The aim was to improve the solubility and oral bioavailability of clozapine. Co-amorphous dispersions were prepared using modified solvent evaporation methodology at drug/plasticizer stoichiometric ratios of 1:1, 1:1.5 and 1:2. Solid state characterization was performed using differential scanning calorimetry, X-ray diffraction and infra red spectroscopy. Highly soluble homogeneous co-amorphous dispersions were formed between clozapine and CAPs via hydrogen bonding. The co-amorphous dispersions formed with tartaric acid (1:2) showed the highest dissolution percentage (> 95 % in 20 minutes) compared to pure crystalline CZ (56 %). Highly stable solutions were obtained from co-amorphous CZ-citric and CZ-tartaric acid at 1:1.5 molar ratio. The prepared dispersions suggest the possibility of peroral or sublingual administration of highly soluble clozapine at a reduced dose with a great chance to bypass the first pass metabolism.

 

Keywords: clozapine, carboxylic acids, co-amorphous systems, plasticizer