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Dissolution-modulating mechanism of alkalizers and polymers in a nanoemulsifying solid dispersion containing ionizable and poorly water-soluble drug
journal contribution
posted on 2009-05-01, 00:00 authored by T T D Tran, Phuong TranPhuong Tran, B J LeeWe investigated the dissolution-modulating mechanism of alkalizers and polymers in nanoemulsifying Gelucire 44/14 (GUC)-based solid dispersions (SDs) for controlled release. Aceclofenac (AFC), an ionizable and poorly water-soluble drug, was chosen because of its extremely low solubility at low pH. Nanoemulsifying SD systems containing alkalizers and/or polymers were prepared by the melting method. Drug crystallinity, microenvironmental pH (pHM), dissolution rate, and droplet size in the media from nanoemulsifying SD were then characterized. Ternary SD containing alkalizers, mainly Na2CO3 and NaHCO3, enhanced the initial release rate of AFC in simulated gastric fluid (pH 1.2), but resulted in spring-like precipitation. However, adding a secondary polymer, Poloxamer 407, prevented precipitation in the quaternary SD system. Poloxamer 407 and alkalizer (Na2CO3) facilitated nanoemulsion formation (80-140 nm) with a smaller droplet size in a medium of pH 1.2 as visualized by TEM. The surface and inner pHM were also modulated by the alkalizers, but not by the polymers. The drug's crystalline structure was further changed to partially or almost amorphous form by the alkalizers and polymers in SD as characterized by instrumental analysis. The synergistic effects of alkalizers and secondary polymers in SD on reduction of drug crystallinity and modulation of pHM via molecular interactions could modulate dissolution rates of ionizable and poorly water-soluble model drug without spring-like precipitation by providing more favorable nanoemulsion-forming environment.
History
Journal
European Journal of Pharmaceutics and BiopharmaceuticsVolume
72Issue
1Pagination
83 - 90Publisher
ElsevierLocation
Amsterdam, The NetherlandsPublisher DOI
ISSN
0939-6411Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2008, Elsevier B.V.Usage metrics
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Dissolution-modulating mechanismNanoemulsifying solid dispersionAlkalizersCrystalline structureMicroenvironmental pHSpring-like precipitationScience & TechnologyLife Sciences & BiomedicinePharmacology & PharmacyWEAKLY BASIC DRUGMATRIX TABLETSDELIVERY-SYSTEMSBIOAVAILABILITYRELEASEENHANCEMENTFORMULATIONEXCIPIENTSPIROXICAM
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