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

Sigma-Aldrich
Ethyl alcohol, Pure, 190 proof, ACS spectrophotometric grade, 95.0%
Sigma-Aldrich
Dichloromethane, anhydrous, ≥99.8%, contains 40-150 ppm amylene as stabilizer
Sigma-Aldrich
Ethanol, BioUltra, for molecular biology, ≥99.8%, (absolute alcohol, without additive, A15 o1)
Sigma-Aldrich
Toluene, anhydrous, 99.8%
Sigma-Aldrich
Ethanol, for residue analysis
Supelco
Ethanol, standard for GC
Sigma-Aldrich
Ethanol, purum, secunda spirit, denaturated with 2% 2-butanone and 0.5% 4-methyl-2-pentanone, S15, ~96% (based on denaturant-free substance)
Sigma-Aldrich
Ethanol, tested according to Ph. Eur.
Sigma-Aldrich
Dichloromethane, suitable for HPLC, ≥99.8%, contains amylene as stabilizer
Sigma-Aldrich
Ethyl acetate, ACS reagent, ≥99.5%
Sigma-Aldrich
Chloroform, contains 100-200 ppm amylenes as stabilizer, ≥99.5%
Sigma-Aldrich
Ethyl acetate, suitable for HPLC, ≥99.7%
Sigma-Aldrich
Ethyl acetate, anhydrous, 99.8%
Sigma-Aldrich
Dichloromethane, contains 40-150 ppm amylene as stabilizer, ACS reagent, ≥99.5%
Sigma-Aldrich
Toluene, ACS reagent, ≥99.5%
Sigma-Aldrich
Chloroform, anhydrous, ≥99%, contains 0.5-1.0% ethanol as stabilizer
Sigma-Aldrich
Benzene, anhydrous, 99.8%
Sigma-Aldrich
Dichloromethane, HPLC Plus, for HPLC, GC, and residue analysis, ≥99.9%, contains 50-150 ppm amylene as stabilizer
Sigma-Aldrich
Chloroform, anhydrous, contains amylenes as stabilizer, ≥99%
Sigma-Aldrich
Chloroform, suitable for HPLC, ≥99.8%, contains 0.5-1.0% ethanol as stabilizer
Sigma-Aldrich
Chloroform, HPLC Plus, for HPLC, GC, and residue analysis, ≥99.9%, contains amylenes as stabilizer
Sigma-Aldrich
Dichloromethane, puriss. p.a., ACS reagent, reag. ISO, ≥99.9% (GC)
Sigma-Aldrich
Ethyl acetate, HPLC Plus, for HPLC, GC, and residue analysis, 99.9%
Sigma-Aldrich
Toluene, suitable for HPLC, 99.9%
Supelco
Benzene, analytical standard
Sigma-Aldrich
Toluene, HPLC Plus, for HPLC, GC, and residue analysis, ≥99.9%
Sigma-Aldrich
Benzene, suitable for HPLC, ≥99.9%
Sigma-Aldrich
Benzene, ACS reagent, ≥99.0%
Sigma-Aldrich
Ethyl alcohol, Pure, 200 proof, meets USP testing specifications
Sigma-Aldrich
Isopropyl acetate, ≥99.6%