Active Ingredients: Azithromycin
As material is fed into the mill, it impacts on the rotating hammers and breaks up into smaller particles.
A screen is located below the hammers, which allows the smaller particles to pass through the openings in the screen. Larger particles are retained in the mill and continue to be broken up by the hammers until the azithromycin particles are fine enough to flow through the screen.
In screening, bulk drug is placed through a mesh screen or series of mesh screens to obtain the desired particle size for the bulk drug. Several methods are known for increasing the particle size of drugs, including, but not limited to, granulation and recrystallization.
Wet granulation, for example, involves the use of a granulating liquid that causes the azithromycin particles to agglomerate and thus increase the particle size. Suitable wet granulation methods for the preparation of azithromycin particles are disclosed in copending U.
Provisional Application Ser. Suitable methods for dry granulating azithromycin particles are disclosed in copending U.
Another method to increase the particle size is to sieve the bulk drug to remove the smaller particles.
Methods of assisting flow, or force feeding, are well known in the art.
Thus, in an alternative embodiment of the present invention, a non-dihydrate azithromycin dry blend can be mechanically processed in a manner to compensate for poor flow properties.
A mechanical force feeder might be used when poor weight control is obtained using a pharmaceutical formulation.
Any additional excipients, such as diluent or dry binder should preferably have good flow characteristics and compactibility. Excipients having good flow properties are readily available.
In the dry blend, of the present invention, excipients suitable for use in direct compression include, but are not limited to, binders, diluents, disintegrants, lubricants, fillers, carriers, and the like.
Binders are used to impart cohesive qualities to a tablet formulation, and thus ensure that a tablet remains intact after compaction. Suitable binder materials include, but are not limited to, microcrystalline cellulose, gelatin, sugars including sucrose, glucose, dextrose and maltodextrin, polyethylene glycol, waxes, natural and synthetic gums, polyvinylpyrrolidone, cellulosic polymers including hydroxypropyl cellulose, hydroxypropyl methylcellulose, methyl cellulose, hydroxyethyl cellulose, and the like.
Lubricants can be employed herein in the manufacture of certain dosage forms, and will usually be employed when producing tablets. In the present invention, a lubricant is added just before the tableting step, and is mixed with the formulation for a minimum period of time to obtain good dispersal.
Preferred lubricants are magnesium stearate, calcium stearate, zinc stearate and mixtures of magnesium stearate with sodium lauryl sulfate.
Suitable disintegrants include, but are not limited to, crosslinked polyvinylpyrrolidone PVP-XL, sodium starch glycolate, and croscarmellose sodium. Suitable diluents or fillers include, but are not limited to, lactose monohydrate, spray-dried monohydrate, anhydrous and the like, sucrose, dextrose, mannitol, sorbitol, starch, cellulose e.
Most preferred free-flowing diluents are spray-dried lactose and free-flowing lactose monohydrate grades, high density and direct compression grades of microcrystalline cellulose and silicified microcrystalline cellulose, spray-dried dextrates, spray-dried and granular mannitol, spray-dried and coarse sorbitol and free-flowing grades of dibasic calcium phosphate, dihydrate.
Also useful as flavors are vanilla, citrus oil, including lemon, orange, grape, lime and grapefruit, and fruit essences, including apple, banana, pear, peach, strawberry, raspberry, cherry, plum, pineapple, apricot, and so forth.
Generally the flavoring will be present in an amount of from 0. For sachets and powders for suspension, the preferred flavoring comprises a combination of cherry, banana and vanilla flavors as further described in Table XIII of U.
The teachings of U.