Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Patent
1995-03-13
1997-05-27
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
424493, 424494, 424499, 424488, 424489, 424456, A61K 916, A61K 950
Patent
active
056330154
DESCRIPTION:
BRIEF SUMMARY
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is based upon PCT Application Serial No. PCT/EP 93/02327, filed Aug. 27, 1993, which claims priority from European patent application Serial No. 92.202.664.6, filed on Sep. 3, 1992.
The present invention is concerned with a novel composition of antifungal agents which have low solubility in aqueous media, a process for preparing said composition and pharmaceutical dosage forms for oral administration comprising said novel composition.
The development of efficaceous pharmaceutical compositions of azole antifungals such as for example, itraconazole and saperconazole, is hampered considerably by the fact that said antifungals are only very sparingly soluble in water. The solubility and bioavailability of said compounds can be increased by complexation with cyclodextrins or derivatives thereof as described in WO 85/02767 and U.S. Pat. No. 4,764,604. Yet, there still exists an important demand for formulations of antifungal agents with good bioavailability for oral administration.
Itraconazole or (.+-.)-cis-4-[4-[4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmet hyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]phenyl]-2,4-dihydro-2- (1-methylpropyl)-3H-1,2,4-triazol-3-one, is a broadspectrum antifungal compound developed for oral, parenteral and topical use and is disclosed in U.S. Pat. No. 4,267,179. Its difluoro analog, saperconazole or (.+-.)-cis-4-[4-[4-[4-[[2-(2,4-difluorophenyl)-2(1H-1,2,4-triazol-1-ylmeth yl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]-phenyl]-2,4-dihydro-2- (1-methoxypropyl)-3H-1,2,4-triazol-3-one, has improved activity against Aspergillus spp. and is disclosed in U.S. Pat. No. 4,916,134.
Unexpectedly, it has now been found that the incorporation of poorly soluble antifungal agents in hydrophilic polymers and applying this mixture as a coat film over many small beads, yields a composition with good bioavailability which can conveniently be manufactured and which is suitable for preparing pharmaceutical dosage forms for oral administration.
In particular the present invention is concerned with beads which comprise (a) a central, rounded or spherical core, (b) a coating film of a hydrophilic polymer and an antifungal agent and (c) a seal-coating polymer layer, characterized in that the core has a diameter of about 600 to about 700 .mu.m (25-30 mesh).
Beads obtainable from 25-30 mesh cores comprise approximately, by weight based on the total weight of the bead: (a) 20 to 60 percent core material; (b) 25 to 50 percent hydrophilic polymer; (c) 10 to 25 percent antifungal agent; and (d) 2 to 5 percent seal coating polymer.
The particular size of the cores is of considerable importance. On the one hand, if the cogs are too large, there is less surface area available for applying the drug coating layer, which results in thicker coating layers. This raises problems in the manufacturing process as an intensive drying step is needed to reduce residual solvent levels in the coating layer. The intense drying conditions may adversely effect drug dissolution from the beads and should therefore be controlled extremely well during the manufacturing process. On the other hand, small cores have a larger total surface available for coating resulting in thinner coating layers. Consequently a far less intensive drying step can be used to decrease residual solvents levels. Cogs which are too small, e.g. 30-35 mesh cores, however, have the disadvantage of showing considerable tendency to agglomerate during the coating process. Therefore, 25-30 mesh cons represent the optimum size where neither agglomeration nor an intensive drying step unduly constraint the manufacturing process.
Materials suitable for use as cores in the beads according to the present invention are manifold, provided that said materials are pharmaceutically acceptable and have appropriate dimensions (about 25-30 mesh) and firmness. Examples of such materials are polymers e.g. plastic resins; inorganic substances, e.g. silica, glass, hydroxyapatite, salts (sodium or pot
REFERENCES:
patent: 4855326 (1989-08-01), Fuisz et al.
patent: 5049374 (1991-09-01), Dansereau et al.
patent: 5213811 (1993-05-01), Frisbee et al.
De Conde Valentin F. V.
Gilis Paul M. V.
Vandecruys Roger P. G.
Benston, Jr. William E.
Metz Charles J.
Page Thurman K.
LandOfFree
Beads having a core coated with an antifungal and a polymer does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Beads having a core coated with an antifungal and a polymer, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Beads having a core coated with an antifungal and a polymer will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2327394