Dissolution of fludrocortisone from phospholipid coprecipitates. 1992

G K Vudathala, and J A Rogers
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.

The physical properties and dissolution behavior of phospholipid coprecipitates of fludrocortisone acetate (FA) prepared from ethyl acetate, as well as the effect of added polymer, have been determined. The fraction dissolved after 90 min and the initial dissolution rate (IDR) of coprecipitates containing dimyristoyl phosphatidylcholine (DMPC) (4:1, w/w; FA:DMPC) were 77% and 3.5-fold greater than for FA at pH 2.0 and 37 degrees C. The mechanisms of dissolution were similar to those previously established for griseofulvin, but no aging occurred over 4 months at room temperature in a desiccator. The addition of 0.01 mol% of dextran (MW = 2 million) or 0.1 mol% of poly(lactic acid) reduced the fraction of FA dissolved in 90 min by 15% and reduced the IDR by 35%. The addition of poly(vinylpyrrolidone) (PVP) resulted in a minimum of dissolution efficiency at 1 mol% of PVP 10 (MW = 10,000) or PVP 24 (MW = 24,000) and at 0.1 mol% PVP 40 (MW = 40,000). Only PVP 24 influenced the melting point and heat of fusion of the coprecipitates (determined by differential thermal analysis). Coprecipitate dissolution was reasonably described by either second-order or Weibull distribution kinetic models. These results support the application of high drug-containing solid dispersions using phospholipids to increase the dissolution behavior of poorly water-soluble drug solvates and the possibility of modifying drug release by the incorporation of small amounts of polymers.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D010743 Phospholipids Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. Phosphatides,Phospholipid
D011108 Polymers Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., BIOPOLYMERS; PLASTICS). Polymer
D011232 Chemical Precipitation The formation of a solid in a solution as a result of a chemical reaction or the aggregation of soluble substances into complexes large enough to fall out of solution. Precipitation, Chemical
D002626 Chemistry, Pharmaceutical Chemistry dealing with the composition and preparation of agents having PHARMACOLOGIC ACTIONS or diagnostic use. Medicinal Chemistry,Chemistry, Pharmaceutic,Pharmaceutic Chemistry,Pharmaceutical Chemistry,Chemistry, Medicinal
D003692 Delayed-Action Preparations Dosage forms of a drug that act over a period of time by controlled-release processes or technology. Controlled Release Formulation,Controlled-Release Formulation,Controlled-Release Preparation,Delayed-Action Preparation,Depot Preparation,Depot Preparations,Extended Release Formulation,Extended Release Preparation,Prolonged-Action Preparation,Prolonged-Action Preparations,Sustained Release Formulation,Sustained-Release Preparation,Sustained-Release Preparations,Timed-Release Preparation,Timed-Release Preparations,Controlled-Release Formulations,Controlled-Release Preparations,Extended Release Formulations,Extended Release Preparations,Slow Release Formulation,Sustained Release Formulations,Controlled Release Formulations,Controlled Release Preparation,Controlled Release Preparations,Delayed Action Preparation,Delayed Action Preparations,Formulation, Controlled Release,Formulations, Controlled Release,Prolonged Action Preparation,Release Formulation, Controlled,Release Formulations, Controlled,Sustained Release Preparation,Timed Release Preparation,Timed Release Preparations
D004134 Dimyristoylphosphatidylcholine A synthetic phospholipid used in liposomes and lipid bilayers for the study of biological membranes. Dimyristoyllecithin,1,2-Dimyristoyl-glycero-3-phosphorylcholine,1,2-Ditetradecanoyl-glycero-3-phosphocholine,1,2-Ditetradecyl-glycero-3-phosphocholine,DMCP,DMPC,1,2 Dimyristoyl glycero 3 phosphorylcholine,1,2 Ditetradecanoyl glycero 3 phosphocholine,1,2 Ditetradecyl glycero 3 phosphocholine
D005438 Fludrocortisone A synthetic mineralocorticoid with anti-inflammatory activity. 9-Fluorocortisol,9 alpha Fludrohydrocortisone,9 alpha-Fluoro-17-Hydroxycorticosterone,9 alpha-Fluorohydrocortisone,9-Fluoro-17-Hydroxycortisone,9-Fluorohydrocortisone,Astonin,Astonin Merck,Astonin-H,FCOL,9 Fluoro 17 Hydroxycortisone,9 Fluorocortisol,9 Fluorohydrocortisone,9 alpha Fluoro 17 Hydroxycorticosterone,9 alpha Fluorohydrocortisone,Astonin H,Merck, Astonin
D012995 Solubility The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed) Solubilities
D012996 Solutions The homogeneous mixtures formed by the mixing of a solid, liquid, or gaseous substance (solute) with a liquid (the solvent), from which the dissolved substances can be recovered by physical processes. (From Grant & Hackh's Chemical Dictionary, 5th ed) Solution

Related Publications

G K Vudathala, and J A Rogers
March 1972, Journal of pharmaceutical sciences,
G K Vudathala, and J A Rogers
September 1987, Chemical & pharmaceutical bulletin,
G K Vudathala, and J A Rogers
January 1999, Pharmaceutical development and technology,
G K Vudathala, and J A Rogers
January 1989, Yao xue xue bao = Acta pharmaceutica Sinica,
G K Vudathala, and J A Rogers
August 1991, Journal of pharmaceutical sciences,
G K Vudathala, and J A Rogers
May 1969, Journal of pharmaceutical sciences,
G K Vudathala, and J A Rogers
January 1995, Drug development and industrial pharmacy,
Copied contents to your clipboard!