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Developing an environmentally benign process for the production of microparticles : Amphiphilic crystallization. / Murnane, Darragh; Marriott, Christopher; Martin, Gary P.

In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 69, No. 1, 05.2008, p. 72-82.

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@article{ba65eb13c4a84705946807dd5a465b81,
title = "Developing an environmentally benign process for the production of microparticles: Amphiphilic crystallization",
abstract = "The production of microparticles for inhalation typically employs jet-milling which can be destructive to the solid-state properties of the particles. The objective of the current work was to develop a crystallization process for the production of respirable microparticles of salmeterol xinafoate (SX) with a controlled particle size distribution (PSD). Solvation of SX in aqueous poly(ethylene glycol) 400 (PEG 400) was investigated using HPLC and FTIR. SX was crystallized from PEG 400 solutions by the addition of water under a variety of conditions of supersaturation, addition rate of antisolvent and stirring speed. The crystals were filtered, dried at 50 degrees C and their PSDs were determined by laser diffraction. A logarithmic increase in solubility of SX was observed with increasing concentration of PEG 400 in water enabling the aqueous antisolvent crystallization of SX from PEG. Similar to antisolvent crystallization from conventional solvents, a 2(4) factorial study showed the particle size to decrease with increasing supersaturation. The PSD also depended on the balance of meso- and micromixing determined by the crystallization conditions. In particular a high addition rate (200 g min(-1)) and low stirrer speed (400 rpm) minimized the median diameter (2.54 +/- 0.40 mu m) and produced a narrow PSD (90{\%} < 8.67 +/- 0.77 mu m) of SX particles. Amphiphilic crystallization provided a novel, environmentally benign method to produce microparticles of SX with a controlled size range. (C) 2007 Elsevier B.V. All rights reserved.",
keywords = "crystallization, antisolvent micronization, factorial design, poly(ethylene glycol), salmeterol xinafoate, INVERSE GAS-CHROMATOGRAPHY, METERED-DOSE INHALERS, DRY POWDER INHALERS, DRUG-DELIVERY, POLYETHYLENE-GLYCOLS, SURFACE ENERGETICS, POLY(ETHYLENE GLYCOL), PRECIPITATION PROCESS, SALMETEROL XINAFOATE, PULMONARY DELIVERY",
author = "Darragh Murnane and Christopher Marriott and Martin, {Gary P.}",
year = "2008",
month = "5",
doi = "10.1016/j.ejpb.2007.10.014",
language = "English",
volume = "69",
pages = "72--82",
journal = "European Journal of Pharmaceutics and Biopharmaceutics",
issn = "0939-6411",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - Developing an environmentally benign process for the production of microparticles

T2 - Amphiphilic crystallization

AU - Murnane, Darragh

AU - Marriott, Christopher

AU - Martin, Gary P.

PY - 2008/5

Y1 - 2008/5

N2 - The production of microparticles for inhalation typically employs jet-milling which can be destructive to the solid-state properties of the particles. The objective of the current work was to develop a crystallization process for the production of respirable microparticles of salmeterol xinafoate (SX) with a controlled particle size distribution (PSD). Solvation of SX in aqueous poly(ethylene glycol) 400 (PEG 400) was investigated using HPLC and FTIR. SX was crystallized from PEG 400 solutions by the addition of water under a variety of conditions of supersaturation, addition rate of antisolvent and stirring speed. The crystals were filtered, dried at 50 degrees C and their PSDs were determined by laser diffraction. A logarithmic increase in solubility of SX was observed with increasing concentration of PEG 400 in water enabling the aqueous antisolvent crystallization of SX from PEG. Similar to antisolvent crystallization from conventional solvents, a 2(4) factorial study showed the particle size to decrease with increasing supersaturation. The PSD also depended on the balance of meso- and micromixing determined by the crystallization conditions. In particular a high addition rate (200 g min(-1)) and low stirrer speed (400 rpm) minimized the median diameter (2.54 +/- 0.40 mu m) and produced a narrow PSD (90% < 8.67 +/- 0.77 mu m) of SX particles. Amphiphilic crystallization provided a novel, environmentally benign method to produce microparticles of SX with a controlled size range. (C) 2007 Elsevier B.V. All rights reserved.

AB - The production of microparticles for inhalation typically employs jet-milling which can be destructive to the solid-state properties of the particles. The objective of the current work was to develop a crystallization process for the production of respirable microparticles of salmeterol xinafoate (SX) with a controlled particle size distribution (PSD). Solvation of SX in aqueous poly(ethylene glycol) 400 (PEG 400) was investigated using HPLC and FTIR. SX was crystallized from PEG 400 solutions by the addition of water under a variety of conditions of supersaturation, addition rate of antisolvent and stirring speed. The crystals were filtered, dried at 50 degrees C and their PSDs were determined by laser diffraction. A logarithmic increase in solubility of SX was observed with increasing concentration of PEG 400 in water enabling the aqueous antisolvent crystallization of SX from PEG. Similar to antisolvent crystallization from conventional solvents, a 2(4) factorial study showed the particle size to decrease with increasing supersaturation. The PSD also depended on the balance of meso- and micromixing determined by the crystallization conditions. In particular a high addition rate (200 g min(-1)) and low stirrer speed (400 rpm) minimized the median diameter (2.54 +/- 0.40 mu m) and produced a narrow PSD (90% < 8.67 +/- 0.77 mu m) of SX particles. Amphiphilic crystallization provided a novel, environmentally benign method to produce microparticles of SX with a controlled size range. (C) 2007 Elsevier B.V. All rights reserved.

KW - crystallization

KW - antisolvent micronization

KW - factorial design

KW - poly(ethylene glycol)

KW - salmeterol xinafoate

KW - INVERSE GAS-CHROMATOGRAPHY

KW - METERED-DOSE INHALERS

KW - DRY POWDER INHALERS

KW - DRUG-DELIVERY

KW - POLYETHYLENE-GLYCOLS

KW - SURFACE ENERGETICS

KW - POLY(ETHYLENE GLYCOL)

KW - PRECIPITATION PROCESS

KW - SALMETEROL XINAFOATE

KW - PULMONARY DELIVERY

U2 - 10.1016/j.ejpb.2007.10.014

DO - 10.1016/j.ejpb.2007.10.014

M3 - Article

VL - 69

SP - 72

EP - 82

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

IS - 1

ER -