Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Processes of preparing a desired or intentional composition...
Utility Patent
1999-05-21
2001-01-02
Sanders, Kriellion (Department: 1714)
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
Processes of preparing a desired or intentional composition...
C523S333000, C523S223000, C524S035000, C524S156000
Utility Patent
active
06169130
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to a method for improving the dispersion of redispersible polymer powders into a solution. In particular, the invention is a method of dispersing redispersible polymer powders, wherein the polymer powders are dispersed into an aqueous solution containing an alkalinizing agent.
BACKGROUND OF THE INVENTION
Dosage forms having an extended drug release profile are manufactured by different industries, including in particular the pharmaceutical and chemical industry. For example, for the treatment of certain diseases, it is advantageous to administer the drug in an extended release form. The use of dosage forms with extended drug release normally leads to a better control of the drug release and therefore of the blood levels, to a reduction in the frequency of dosing and to a lower total drug dose. With these extended drug release systems, the drug is released either at a constant or at a decreasing rate over an extended period of time.
Dosage forms with extended drug release are prepared by coating solid drugcontaining dosage forms, like tablets or pellets, with polymer solutions or -dispersions. The polymer coating forms the diffusion barrier and retards the drug release. The polymers, in either organic or aqueous systems, are coated onto the dosage form in pans or fluidized bed equipment. Organic polymer solutions generally yield films of acceptable quality; however, the use of organic solvents in the pharmaceutical industry is problematic and is not preferred due to environmental, toxicity, explosion hazards, and residual solvent concerns.
Aqueous polymers dispersions instead of organic polymer solutions are, therefore, generally preferred for coating solid dosage forms. In aqueous polymer dispersions, the polymer is finely dispersed in water. The film formation from aqueous polymer dispersions occurs after the evaporation of water during the coating process through coalescence (fusion) of the polymer particles at temperatures above the minimum film formation temperature (MFT) in an ideally homogeneous film.
Polymer dispersions are two-phase systems, consisting of a dispersed colloidal polymer phase and an aqueous phase, which is the dispersion vehicle. The techniques for the preparation of polymer dispersions are either emulsion polymerization with water-insoluble monomers (latex-dispersions) or physical preparation methods, which use an already synthesized polymer. In the latter technique, a polymer solution or -melt is emulsified and homogenized in an aqueous phase. The polymer dispersion is obtained after evaporation of the solvent or cooling of the aqueous phase to form a pseudo-latex dispersion.
Acrylic polymers (for example, Eudragit™ polymers) or cellulose derivatives are frequently used as water-insoluble polymers, which are insoluble in the gastrointestinal tract. Ethylcellulose is frequently used as a water-insoluble cellulose derivative coating. Aquacoat™ is an aqueous ethylcellulose pseudo-latex dispersion with a solids content of approximately 30%, which, aside from the polymer, contains the surfactants cetyl alcohol and sodium lauryl sulfate. Another commercially available ethylcellulose dispersion is Surelease™, in which ethylcellulose particles are stabilized with ammonium oleate. The Surelease™ dispersion also contains a plasticizer.
The use of aqueous polymer dispersions is much more complex than the use of organic polymer solutions. Several additives generally have to be added for the preparation or stabilization of the dispersion. Examples of the additives include surfactants, which stabilize the dispersion during preparation and storage; plasticizers, which lower the minimum film formation temperature; and preservatives, which protect the aqueous dispersion from microbial growth. These additives can affect the film formation and also the drug release behavior.
Aqueous polymer dispersions are generally also susceptible to physical and chemical damage. For example, the dispersions are sensitive towards temperature variations or high shear forces, which can lead to the flocculation of the dispersion, or sedimentation of the polymer particles. In addition, polymers, which are chemically degraded in water, cannot generally be used. Susceptibility to microbiological degradation or contamination is also a problem. The shelf life of aqueous polymer dispersions is therefore critical to acceptable performance. However, the shelf life is generally a maximum of one year.
For the above reasons, redispersible polymer powders, which are redispersed to form an aqueous polymer dispersion just prior to their application onto solid dosage forms have been prepared from several aqueous polymer dispersions. These redispersible polymer powders are generally prepared from aqueous polymer dispersions through drying processes such as spray drying. The advantages of these water-free redispersible polymers include improved storage stability, reduced transport and storage costs, and greater flexibility in the preparation of coating formulations.
With the redispersible polymer powders, it is important that the properties of the original polymer dispersions be retained after dispersion of the redispersible polymer powder in water. It is especially important that the original particle size distribution be retained because changes in the particle size distribution—for example, through the formation of agglomerates—can negatively affect the fusion of the particles (coalescence) in a homogeneous polymer film during coating.
Several redispersible polymer powders are commercially available. Aquateric™ is a spray-dried redispersible polymer powder made of cellulose acetate phthalate (CAP). CAP is, however, hydrolytically unstable. Prior to spray-drying the CAP, acetylated monoglycerides, which eliminate the coalescence of the polymer particles during drying and storage and which result in a good wetability of the redispersible polymer powders during redispersion, are added to the aqueous CAP-dispersion. Redispersible polymer powders containing polymers having ionizable functional groups (for example, carboxyl groups or ammonium groups) are also available. These polymers, which include, for example, spray-dried Eudragit™ L or RS 30 D, redisperse well because of their good wetability.
Presently, there are no redispersible polymer powders comprising water-insoluble polymers, such as nonionic polymers, which are commercially available for coating drugs. These polymers are primarily ethylcellulose and cellulose acetate. Although, aqueous polymer dispersions of these polymers can be converted into polymer powders through spray drying, the polymer powders are not redispersible. When these polymer powders are redispersed into an aqueous solution, they form larger agglomerates of particles such that the polymer dispersion does not retain its original particle size distribution. This agglomeration is due to the poor wetability of the water-insoluble polymers and the lack of stabilizing functional groups in the polymer. These larger polymer agglomerates lead to rapid sedimentation and result in an insufficient film formation during dosage form coating. Again, the particle size distribution of the redispersed polymer in solution is an important parameter. Generally, small particle sizes in the colloidal range are preferred for preparing films or coatings of acceptable quality.
Accordingly, a need exists for an improved method of dispersing redispersible polymer powders of nonionic polymers to form polymer dispersions which are suitable for coating dosage forms.
SUMMARY OF THE INVENTION
In the present invention, surprisingly, a good redispersibility of powders of nonionic polymers, which were prepared through spray- or freeze-drying of aqueous polymer dispersions, was obtained.
In one aspect, the invention provides a method of dispersing a redispersible polymer powder in an aqueous solution, wherein the redispersible polymer powder has been prepared by drying an aqueous polymer dispersion of a nonionic polymer, the method comprising the step of:
(a) adding the
Bodmeier Roland
McGinity James W.
Innovar L.L.C.
Matos Rick
Sanders Kriellion
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