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Merck

Effect of binder liquid type on spherical crystallization.

Drug development and industrial pharmacy (2013-08-14)
Maryam Maghsoodi, Ali Hajipour
ABSTRACT

Spherical crystallization is a process of formation of agglomerates of crystals held together by binder liquid. This research focused on understanding the effect of type of solvents used as binder liquid on the agglomeration of crystals. Carbamazepine and ethanol/water were used respectively as a model drug and crystallization system. Eight solvents as binder liquid including chloroform, dichloromethane, isopropyl acetate, ethyl acetate, n-hexane, dimethyl aniline, benzene and toluene were examined to better understand the relationship between the physical properties of the binder liquid and its ability to bring about the formation of the agglomerates. Moreover, the agglomerates obtained from effective solvents as binder liquid were evaluated in term of size, apparent particle density and compressive strength. In this study the clear trend was observed experimentally in the agglomerate formation as a function of physical properties of the binder liquid such as miscibility with crystallization system. Furthermore, the properties of obtained agglomerates such as size, apparent particle density and compressive strength were directly related to physical properties of effective binder liquids. RESULTS of this study offer a useful starting point for a conceptual framework to guide the selection of solvent systems for spherical crystallization.

MATERIALS
Product Number
Brand
Product Description

USP
Carbamazepine, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
N,N-Dimethylaniline, 99%
Sigma-Aldrich
N,N-Dimethylaniline, purified by redistillation, ≥99.5%
Sigma-Aldrich
Chloroform, anhydrous, ≥99%, contains 0.5-1.0% ethanol as stabilizer
Supelco
Ethanol solution, certified reference material, 2000 μg/mL in methanol
Supelco
Dehydrated Alcohol, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Chloroform, suitable for HPLC
USP
Dehydrated Alcohol, United States Pharmacopeia (USP) Reference Standard
Supelco
Chloroform, analytical standard
Sigma-Aldrich
Isopropyl acetate, ≥99%, FCC
Sigma-Aldrich
Chloroform, ACS reagent, ≥99.8%, contains 0.5-1.0% ethanol as stabilizer
Sigma-Aldrich
Rhein, technical grade
Supelco
Chloroform, suitable for HPLC, ≥99.8%, contains 0.5-1.0% ethanol as stabilizer
Sigma-Aldrich
N,N-Dimethylaniline, ReagentPlus®, 99%
Sigma-Aldrich
Chloroform, ACS reagent, ≥99.8%, contains amylenes as stabilizer
Sigma-Aldrich
Carbamazepine, meets USP testing specifications
Supelco
Ethanol standards 10% (v/v), 10 % (v/v) in H2O, analytical standard
Sigma-Aldrich
Ethanol Fixative 80% v/v, suitable for fixing solution (blood films)
Sigma-Aldrich
Carbamazepine, powder
Sigma-Aldrich
Rhein
Sigma-Aldrich
Chloroform, anhydrous, contains amylenes as stabilizer, ≥99%
Sigma-Aldrich
Ethanol, 94.8-95.8%
Supelco
Isopropyl acetate, analytical standard
Supelco
Carbamazepine, Pharmaceutical Secondary Standard; Certified Reference Material
Carbamazepine, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Chloroform, biotech. grade, ≥99.8%, contains 0.5-1.0% ethanol as stabilizer
Sigma-Aldrich
Chloroform, ≥99%, PCR Reagent, contains amylenes as stabilizer
Supelco
Residual Solvent - Toluene, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Chloroform, ReagentPlus®, ≥99.8%, contains 0.5-1.0% ethanol as stabilizer
Supelco
Carbamazepine, analytical standard