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Improved dissolution and pharmacokinetic behavior of dipyridamole formulation with microenvironmental pH-modifier under hypochlorhydria.
- Source :
-
International journal of pharmaceutics [Int J Pharm] 2012 Apr 15; Vol. 426 (1-2), pp. 61-66. Date of Electronic Publication: 2012 Jan 14. - Publication Year :
- 2012
-
Abstract
- The present study aimed to develop and characterize new formulations of dipyridamole (DP), a pH-dependent poorly soluble drug, employing an acidic pH-modifier for improving dissolution and absorption under hypochlorhydric condition. Granule formulations of DP (DPG) with and without fumaric acid (FA) were prepared with wet granulation, physicochemical properties of which were characterized focusing on morphology, dissolution and stability. Pharmacokinetic profiling of orally dosed DPG or DPG with 60% loading of FA (DPG/FA60) was carried out in omeprazole-treated rats as a hypochlorhydric model. Although pH-dependent dissolution behavior was observed in DPG, DPG/FA exhibited high rate and extent of dissolution in both acidic and neutral media. Complete supersaturation was achieved with a 2 h testing period in pH6.8 medium, and co-existing fumaric acid had no impact on the chemical/photochemical stability of DP in solid-state. After oral administration of DPG or DPG/FA60 (10 mg-DP/kg), there was ca. 40% reduction of AUC(0-3) for DPG in omeprazole-treated rats as compared to that in normal rats; however, AUC(0-3) for DPG/FA60 under hypochlorhydria was almost identical to that of DPG in normal rats. Given the improved systemic exposure early after oral administration in hypochlorhydric rats, the DPG/FA might provide better clinical outcomes in hypochlorhydric patients.<br /> (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Subjects :
- Achlorhydria chemically induced
Administration, Oral
Animals
Area Under Curve
Biological Availability
Chemistry, Pharmaceutical
Chromatography, Liquid
Crystallization
Crystallography, X-Ray
Dipyridamole administration & dosage
Dipyridamole chemistry
Disease Models, Animal
Drug Compounding
Drug Stability
Fumarates chemistry
Half-Life
Hydrogen-Ion Concentration
Male
Metabolic Clearance Rate
Microscopy, Electron, Scanning
Omeprazole
Phosphodiesterase Inhibitors administration & dosage
Phosphodiesterase Inhibitors chemistry
Powder Diffraction
Rats
Rats, Sprague-Dawley
Solubility
Spectrometry, Mass, Electrospray Ionization
Technology, Pharmaceutical methods
Achlorhydria metabolism
Dipyridamole pharmacokinetics
Phosphodiesterase Inhibitors pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3476
- Volume :
- 426
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- International journal of pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 22266536
- Full Text :
- https://doi.org/10.1016/j.ijpharm.2012.01.014