Izvorni znanstveni članak

https://doi.org/10.1515/acph-2015-0014

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

AHMED MAHMOUD ABDELHALEEM ALI orcid.org/0000-0002-4370-007X ; Department of pharmaceutics, Faculty of Pharmacy, Beni Suef University, Egypt; Department of clinical pharmacy, Faculty of Pharmacy, Taif University, Kingdom Saudi Arabia
ADEL AHMED ALI ; Department of pharmaceutics, Faculty of Pharmacy, Beni Suef University, Egypt
IBRAHIM ABDULLAH MAGHRABI ; Department of clinical pharmacy, Faculty of Pharmacy, Taif University, Kingdom Saudi Arabia

Sažetak

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.

Ključne riječi

clozapine; carboxylic acids; co-amorphous systems; plasticizer

Hrčak ID:

128993

URI

https://hrcak.srce.hr/128993

Datum izdavanja:

30.6.2015.

Posjeta: 2.227 *