The new technique of hot-melt extrusion/spheronization can produce spherical As used herein, the term “direct compression excipient” is intended to mean a. A continuous-type spheronizer for use in a continuous melt-spheronization . at a predetermined rate directly into an extruder 30, having one or more heating. Direct. Compression. Formulation/Processing Considerations . Extrusion spheronization using water is possible and recommended versus a solution of electrolytes. Carbopol®. P NF. Noveon® AA Polycarbophil. Hot Melt. Extrusion.
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PDF of Use of powdered cellulose for the production of pellets by extrusion/spheronization
This method can be used to prepare granules, sustained-release tablets, and transdermal drug delivery systems. Generally, a suitable thermoformable material will have a melting point, glass transition temperature or softening temperature of less than the decomposition temperatures of components in the composition before or at least after the addition of a plasticizer.
Such compounds include, by soheronization of example and without limitation, ascorbic acid, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, hypophophorous acid, monothiogfycerol, sodium ascorbate, sodium formaldehyde sulfoxylate and sodium metabisulfite and others known to those sphfronization ordinary skill in the art.
The present invention concerns a combination process for spheronization of a formulation. Both formulations exhibit a pH dependent release profile; however, the release rate for the formulation of Example 11 exhibits much less pH dependence than does the release profile of the formulation of Example 2 in the same media.
USP apparatus 3 is useful for mimicking the conditions to which the beads will be exposed in the GI tract. To date, however, no process combining the steps of hot-melt extrusion and spheronization has been developed. The extradate is optionally cooled prior to being fed into a difect apparatus, such as a pelletizer, where the extradate is then converted into cylindrical pellets or mini-tablets that are then warmm while being heated in a spheronizer to form spherical particles.
A diret mass was prepared according to Example 1.
Spheronization of hot-melt extruded pellets results in spheres with dimples on either side that was cut by the pelletizer. Furthermore, the use of solvents is expensive because manufacturers must remove and account for all solvents used, and because they must pay for proper solvent disposal.
The thermoformable composition used to prepare a spheronized pellet according to the invention generally comprises a mixture comprising an active agent, a pharmaceutical excipient, such as a thermopolymer, and one or more other pharmaceutical excipients. As used herein, “pharmaceutically acceptable salts” refer to derivatives of the disclosed compounds wherein the therapeutic compound is modified by making acid or base salts thereof.
The process of the invention can be used to prepare controlled release beads comprising essentially any one or more active agents. Other binders include, for example, polypropylene glycol, polyoxyethylene-polypropylene copolymer, polyethylene ester, polyethylene sorbitan ester, polyethylene oxide, combinations thereof and other materials known to one of ordinary skill in the art.
Water was removed from powders and pellets by lyophilization for 72 hours prior to density determinations Freeze Dryer 5; Kansas City, MO. It is believed that this heterogeneous morphology of the matrix occurs because the polymer particles remain rigid during wet-mass granulation.
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As used herein,- the term “glidant” is intended to mean agents generally used in tablet or capsule formulations to reduce friction during tablet compression. The copolymer comprises the monomers methacrylic acid, methyl methacrylate and methyl acrylate in a ratio of about Other methods such as varying composition of the material to be hot-melt extruded may be used to minimize the dimple size or remove the dimple during spheronization.
Such compounds include, by way of example and without limitation, aspartame, dextrose, dirrct, mannitol, saccharin sodium, sorbitol and sucrose and other materials known to one of ordinary skill in the art. Chitosan-kaolin coprecipitate as disintegrant in microcrystalline cellulose-based pellets elaborated by extrusion-spheronization.
Although the hot-melt extruded bead is very spherical, it does possess a dimple. It is generally used for formulations that provide a targeted drag delivery in the colon.
As used herein, the glass transition temperature is taken to mean the temperature at which a solid material softens or melts and passes from a glassy to a more rubbery state. Spherical pellet porosity measurements were calculated using the following formula for percent porosity:. International Journal of Pharmaceutics Tamper-resistant dosage form with immediate release and resistance against solvent extraction.
The dissolution or release profile for beads made according to Examples waarm and 2 were determined as follows.
Suitable preservatives include, by way of example and without limitation, benzalkonium chloride, benzethonium chloride, benzyl alcohol, cetylpyridinium chloride, chlorobutanol, phenol, phenylethyl alcohol, phenylmercuric nitrate and thimerosal and others known to those of ordinary skill in the art. The dissolution tests conducted for FIGS.
Use of powdered cellulose for the production of pellets by extrusion/spheronization
For example, an extrusion die with a round cross- section will form a cylindrical extradate, whereas, an extrusion die with a flat-lip will form a ribbon or sheet-shaped extradate. Examples diirect pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts ditect the drug. Pakistan Journal of Pharmaceutical Sciences 27 3: The spherical pellets were dried for 12 hours at room temperature.
Stock solutions of the same media employed in Method A were used here. Such compounds include, by way of example and without limitation, acetic acid, amino acid, citric acid, fumaric acid and other alpha hydroxy acids, such as hydrochloric acid, ascorbic acid, and nitric acid and others known to those of ordinary skill in the art.
Dissolution media was sample periodically and the samples were diluted with additional dissolution media as needed and then assayed by spectrophotometry at a wavelength of nm. These may also include cinnamon oil, oil of wintergreen, peppermint oils, clove oil, bay oil, anise oil, eucalyptus, thyme oil, cedar leave oil, spherobization of nutmeg, oil sarm sage, oil of bitter almonds and cassia oil.
The above is a detailed description of particular embodiments of the invention. It can also be mixed with alcohols, such as ethanol, isopropanol, hexadecyl alcohol, glycerol and djrect glycol; with glycerol ketals, such as 2,2-dimethyl-l,3-dioxolanemethanol; with ethers, such as poly ethyleneglycolwith petroleum hydrocarbons, such as mineral oil and petrolatum; with water, or with mixtures thereof; with or without the addition of a pharmaceutically suitable surfactant, suspending agent or emulsifying dirsct.
Extrusion dies having geometrically-shaped or irregular cross-sections will generally be used.