Active substances: Azithromycin
Common allergy drug makes resistant bacteria vulnerable to antibiotics Chloroquine and hydroxychloroquine, a pair of old drugs used to treat and prevent malaria, are the latest compounds to be thrust into the limelight as people tout them as treatments for the novel coronavirus.
An especially preferred embodiment is a capsule shell in the form of an asymmetric membrane; i. A preferred process for preparation of asymmetric membrane capsules comprises a solvent exchange phase inversion, wherein a solution of polymer, coated on a capsule-shaped mold, is induced to phase-separate by exchanging the solvent with a miscible non-solvent.
Examples of asymmetric membranes useful in this invention are disclosed in the aforementioned European Patent Specification 0 357 369 B 1. A preferred embodiment of the class of reservoir systems comprises a multiparticulate wherein each particle is coated with a polymer designed to, yield sustained release of azithromycin.
The multiparticulate particles each, comprise azithromycin and one or more excipients as needed for fabrication and performance. In general, the beads comprise azithromycin and one or more binders.
As it is generally desirable to produce dosage forms which are small and easy to swallow, beads which contain a high fraction of azithromycin relative to excipients are preferred. Binders useful in fabrication of these beads include microcrystalline cellulose e.
Advantageously, azithromycin can be loaded in the aqueous composition beyond its solubility limit in water. Suitable and preferred polymer coating materials, equipment, and coating methods also include those previously discussed.
The rate of azithromycin release from the coated multiparticulates can also be controlled by factors such as the composition and binder content of the drug containing core, the thickness and permeability of the coating, and the surface-to-volume ratio of the multiparticulates.
It will be appreciated by those skilled in the art that increasing the thickness of the coating will decrease the release rate, whereas increasing the permeability of the coating or the surface-to-volume ratio of the multiparticulates will increase the release rate.
A useful series of coatings comprises mixtures of water-insoluble and water-soluble polymers, for example, ethylcellulose and hydroxypropyl methylcellulose, respectively.
A particularly useful modification to the coating is the addition of finely-divided water-soluble material, such as sugars or salts. When placed in aqueous medium, these water soluble membrane additives are leached out of the membrane, leaving pores which facilitate delivery of the drug.
A particularly useful variation of the membrane coating utilizes a mixture of solvents chosen such that as the coating dries, a phase inversion takes place in the applied coating solution, resulting in a membrane with a porous structure.
Osmotic pumps comprise a core containing an osmotically effective composition surrounded by a semipermeable membrane.
In use, when placed in an aqueous environment, the device imbibes water due to the osmotic activity of the core composition.
Owing to the semipermeable nature of the surrounding membrane, the contents of the device including the drug and any excipients cannot pass through the non-porous regions of the membrane and are driven by osmotic pressure to leave the device through an opening or passageway pre-manufactured into the dosage form, alternatively, formed in situ in the GI tract as by the bursting of intentionally-incorporated weak points in the coating under the influence of osmotic pressure.
The osmotically effective composition includes water-soluble species, which generate a colloidal osmotic pressure, and water-swellable polymers. Therefore, the osmotic effectiveness of azithromycin depends on the presence of acidic buffers in the formulation.
Materials useful for forming the semipermeable membrane include polyamides, polyesters, and cellulose derivatives.
Preferred are cellulose ethers and esters. Especially preferred are cellulose acetate, cellulose acetate pille, and ethyl cellulose.
Especially useful materials include those which spontaneously form one or more exit passageways, either during manufacturing or when placed in an environment of use.
These preferred materials comprise porous polymers, the pores of which are formed by phase inversion during manufacturing, as described above, or by dissolution of a water-soluble component present in the membrane.
A class of materials which have particular utility for forming semipermeable membranes for use in osmotic delivery devices is that of porous hydrophobic polymers, as disclosed by commonly assigned co-pending U.