Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Food or edible as carrier for pharmaceutical
Reexamination Certificate
1998-12-16
2002-04-16
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Food or edible as carrier for pharmaceutical
C424S464000, C424S489000, C427S002140, C427S472000
Reexamination Certificate
active
06372246
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to substrate coatings for the electrostatic deposition of dry powder medicaments for use in the manufacture of pharmaceutical dosage forms. The invention also relates to the technology of reversing negative charge of medicaments so that they can be deposited on a negatively charged substrate. More particularly, the invention relates to polyethylene glycol substrate coatings for the dry powder electrostatic deposition of medicinal substances. The invention also provides the means of employing polyethylene glycol to reverse the negative charge of medicaments so that they can be deposited on a negatively charged substrate.
BACKGROUND OF THE INVENTION
It has been proposed for sometime that dry powdered medicaments be delivered orally by electrostatically depositing the dry medicament onto an edible substrate which could be administered to the patient. The substrate with the medicament deposited thereon is administered to the patient directly or is applied to a placebo tablet which can be administered to the patient. The technology has potential advantages in enhanced safety, enhanced stability, and efficient product development and manufacturing.
One example of this technique is disclosed in U.S. Pat. No. 4,197,289 (the '289 patent). This patent discloses solid unit dosage forms for oral administration comprising an edible “web” having the medicament deposited thereon where the web is fabricated into a dosage form in which the deposited medicament is sealed. The dosage forms are manufactured by using an electrostatic charging technique. In this technique, the edible web is passed through an electrostatic field in a suitable chamber. Finely particulate active ingredient is introduced into the chamber and is deposited onto the web as it passes over an oppositely charged roller. Dosages are regulated by measuring spectroscopically the amount of medicament that has been deposited on the web and fabricating an appropriate dosage form with the required amount of medicament. In this technique, the edible web used for depositing the medicament is an edible material with a resistivity capable of enabling the deposition thereon of dielectric particles. Paper and polymeric web formulations are disclosed. The polymeric webs are prepared from an organic film forming polymer such as cellulose derivatives in combination with plasticizers, modifiers and fugitive solvents.
Another technique is disclosed in U.S. Pat. No. 5,714,007 (the '007 patent). In this patent there is disclosed an apparatus and method for electrostatically depositing select doses of medicament powder at select locations on a substrate. The '007 patent technique involves charging a predefined region of a substrate with a controlled amount of charge. Oppositely charged medicament powder is then exposed to the charged substrate so that the powder medicament adheres to the charged substrate. The quantity and position of charge accumulated on the substrate and the charge-to-mass ratio of the medicament powder can be used to accurately control the dosage of medicament applied to the substrate and the position of the medicament on the substrate. The substrate is then encapsulated in an inert material to form a capsule, tablet, or suppository. It is suggested that the substrates can vary widely depending upon the ultimate application of the medication. For oral medications, polymeric substances such as cellulose are disclosed.
In each of these techniques it is suggested that the dry powder can be applied directly to the surface of the edible substrate and the substrate can either be divided into unit dosage forms or encapsulated in an inert material to form a capsule, tablet or suppository. In either case, when the dry medicament powder is deposited directly onto a dosage form substrate, a coating is required. The deposited drug powder is as loose as dust on the surface of a furniture. To prevent drug powder from being wiped off or from losing potency during subsequent processing and packaging, the product needs a protective coating.
Various materials are used as film coatings in tablet manufacture but in practice conventional polymeric coatings are not all suitable. Polymeric films typically used in such film coating include (1) vinyl polymers such as polyvinylpyrrolidone, polyvinyl alcohol and acetate, (2) cellulosics such as methyl and ethyl cellulose, hydroxyethyl cellulose and hydroxypropyl methylcellulose, (3) acrylates and methacrylates, (4) copolymers such as the vinyl-maleic acid and styrene-maleic acid types, and (4) natural gums and resins such as zein, gelatin, shellac and acacia. See Remington's Pharmaceutical Sciences, 15th Ed. Mack Publishers (1975) p. 1613.
For the present purposes, the coating needs to be applied to the individual dosage forms precisely and in place. The conventional coating of tablets is random coating. The process includes spraying the coating solution onto a tablet bed while the tablet bed is tumbling in a coating pan. A coating film is formed on the tablets when water or solvent is dried at elevated temperature during coating. The conventional coating is suitable for conventional pharmaceutical dosage forms, tablets or capsules, since the drug substance is embedded or encapsulated in the tablet matrix or capsules. But the conventional coating is not suitable for deposited tablets produced by Electrostatic Dry Deposition technology due to the tumbling of the tablet bed. The coating should be in-place: the deposited tablet or product needs to be coated before it comes in contact with other tablets. In the mean time, the coating should be precise: all coating solution should be on the tablet. Any spill may cause insulation of or interference with the electronic equipment. Accordingly, there is a need for a protective substrate coating which is suitable for the electrostatic deposition of dry powder medicaments which can be applied in place and precisely.
Another problem that is encountered in the above described electrostatic deposition method is that the triboelectric charging process generally produces positively charged drug substances and negatively charged substrate. However, some drug substances can only be negatively charged and would not be suitable for use with a negatively charged substrate. Accordingly, a need exists for a method of depositing negatively charged drug substance on a negatively charged substrate.
SUMMARY OF THE INVENTION
The invention relates to a substrate coating for the electrostatic deposition of dry powder medicaments for use in the manufacture of pharmaceutical dosage forms comprising micronized polyethylene glycol (PEG), with molecular weight in the range of 1,000 to 20,000, and having a particle size of 1-100 &mgr;m.
The invention also relates to an improvement in the process for manufacturing pharmaceutical unit dosage forms by triboelectric charging and the electrostatic deposition of dry powder medicament to a substrate, the improvement comprising coating the substrate in place with dry micronized polyethylene glycol (PEG), melting the dry polyethylene glycol coating and allowing it to cool whereupon a protective coating is formed.
In a further aspect of the invention, a method of depositing negatively charged dry powder medicament on a negatively charged substrate by an electrostatic dry powder deposition process is provided, the method comprising reversing the charge of the medicament to a positive charge by mixing the negatively charged medicament with micronized polyethylene glycol (PEG), at the ratio of medicament to PEG of 1:1 to 1:40, and then depositing the mixture onto the negatively charged substrate. Once the charged mixture is deposited on the substrate surface, it is melted and cooled whereupon a protective film is formed while cooling.
In a further aspect of the invention, a pharmaceutical composition is provided comprising an edible substrate having micronized drug substance with a particle size of 1-100 &mgr;m, preferably 5-20 &mgr;m, deposited on the surface of the substrate by elec
Uang Herling
Wei Shifeng Bill
Ciambrone Coletti Ellen
Ortho-McNeil Pharmaceutical , Inc.
Page Thurman K.
Seidleck Brian K.
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