Adsorption of pharmaceutical excipients onto microcrystals of siramesine hydrochloride : Effects on physicochemical properties
(2009) In European Journal of Pharmaceutics and Biopharmaceutics 71(1). p.109-116- Abstract
A common challenge in the development of new drug substances is poor dissolution characteristics caused by low aqueous solubility. In this study, microcrystals with optimized physicochemical properties were prepared by precipitation in the presence of excipients, which adsorbed to the particle surface and altered particle size, morphology, and dissolution rate. The poorly water-soluble drug siramesine hydrochloride was precipitated by the antisolvent method in the presence of each of various polymeric and surface active excipients. Powder dissolution studies of six of the resulting particle systems showed a significant increase in percent dissolved after 15 min compared to the starting material. A quantitative determination of the... (More)
A common challenge in the development of new drug substances is poor dissolution characteristics caused by low aqueous solubility. In this study, microcrystals with optimized physicochemical properties were prepared by precipitation in the presence of excipients, which adsorbed to the particle surface and altered particle size, morphology, and dissolution rate. The poorly water-soluble drug siramesine hydrochloride was precipitated by the antisolvent method in the presence of each of various polymeric and surface active excipients. Powder dissolution studies of six of the resulting particle systems showed a significant increase in percent dissolved after 15 min compared to the starting material. A quantitative determination of the amount of excipient adsorbed to the surface of the drug particles proved that only a very small amount of excipient was needed to exert a marked effect on particle properties. The adsorbed amount of excipient constituted less than 1.4% (w/w) of the total particle weight, and thus powders of very high drug loads were obtained. Sodium lauryl sulphate (SLS), hydroxypropyl methylcellulose (HPMC), and hydroxypropyl cellulose (HPC), which exhibited the greatest degree of adsorption, also had the greatest effect on the physicochemical properties of the particles. X-ray Photoelectron Spectroscopy (XPS) analysis of the surface composition and scanning electron microscopy studies on particle morphology suggested that the excipients adsorbed to specific faces of the crystals.
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- author
- Zimmermann, Anne ; Millqvist-Fureby, Anna LU ; Elema, Michiel Ringkjøbing ; Hansen, Tue LU ; Müllertz, Anette and Hovgaard, Lars
- publishing date
- 2009-01
- type
- Contribution to journal
- publication status
- published
- keywords
- Antisolvent precipitation, Crystal habit, Dissolution rate, Excipient adsorption, Microcrystals, Particle size, Polymers, Poorly soluble drugs, Surfactants, XPS
- in
- European Journal of Pharmaceutics and Biopharmaceutics
- volume
- 71
- issue
- 1
- pages
- 8 pages
- publisher
- Elsevier
- external identifiers
-
- scopus:57349160561
- pmid:18619536
- ISSN
- 0939-6411
- DOI
- 10.1016/j.ejpb.2008.06.014
- language
- English
- LU publication?
- no
- id
- 14985d9b-f39e-46f1-83db-9a650c162806
- date added to LUP
- 2025-04-02 22:35:11
- date last changed
- 2025-04-16 23:20:27
@article{14985d9b-f39e-46f1-83db-9a650c162806,
abstract = {{<p>A common challenge in the development of new drug substances is poor dissolution characteristics caused by low aqueous solubility. In this study, microcrystals with optimized physicochemical properties were prepared by precipitation in the presence of excipients, which adsorbed to the particle surface and altered particle size, morphology, and dissolution rate. The poorly water-soluble drug siramesine hydrochloride was precipitated by the antisolvent method in the presence of each of various polymeric and surface active excipients. Powder dissolution studies of six of the resulting particle systems showed a significant increase in percent dissolved after 15 min compared to the starting material. A quantitative determination of the amount of excipient adsorbed to the surface of the drug particles proved that only a very small amount of excipient was needed to exert a marked effect on particle properties. The adsorbed amount of excipient constituted less than 1.4% (w/w) of the total particle weight, and thus powders of very high drug loads were obtained. Sodium lauryl sulphate (SLS), hydroxypropyl methylcellulose (HPMC), and hydroxypropyl cellulose (HPC), which exhibited the greatest degree of adsorption, also had the greatest effect on the physicochemical properties of the particles. X-ray Photoelectron Spectroscopy (XPS) analysis of the surface composition and scanning electron microscopy studies on particle morphology suggested that the excipients adsorbed to specific faces of the crystals.</p>}},
author = {{Zimmermann, Anne and Millqvist-Fureby, Anna and Elema, Michiel Ringkjøbing and Hansen, Tue and Müllertz, Anette and Hovgaard, Lars}},
issn = {{0939-6411}},
keywords = {{Antisolvent precipitation; Crystal habit; Dissolution rate; Excipient adsorption; Microcrystals; Particle size; Polymers; Poorly soluble drugs; Surfactants; XPS}},
language = {{eng}},
number = {{1}},
pages = {{109--116}},
publisher = {{Elsevier}},
series = {{European Journal of Pharmaceutics and Biopharmaceutics}},
title = {{Adsorption of pharmaceutical excipients onto microcrystals of siramesine hydrochloride : Effects on physicochemical properties}},
url = {{http://dx.doi.org/10.1016/j.ejpb.2008.06.014}},
doi = {{10.1016/j.ejpb.2008.06.014}},
volume = {{71}},
year = {{2009}},
}