SUSTAINED RELEASE THEOPHYLLINE

THEOPHYLLINE A LIBERATION CONTINUE

English Abstract

ABSTRACT OF DISCLOSURE
Theophylline is provided in a sustained release
formulation which comprises a plurality of micropellets
of theophylline which is coated over a seed in a first
coat with polyvinylpyrrolidone and a second coat of
cellulose derivatives. The sustained release theo-
phylline form is sprinkled into the normal food of a
patient, particularly a child or elderly patient.

Claims

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WHAT IS CLAIMED IS:

1. A sustained release dosage formulation of theo-
phylline which comprises a container having therein a
plurality of micropellets, the sum of such micropellets
in said container forming a dosage unit of theophylline,
each of siad micropellets being based upon a seed having
coated thereon a mixture of theophylline and
polyvinylpyrrolidone, the thus coated seed having further
coated thereon a mixture of cellulose derivatives.
2. A sustained release dosage formulation of claim
1 wherein said cellulose derivative is selected from the
group consisting of hydroxypropyl cellulose and ethyl
cellulose.
3. A sustained release dosage formulation of claim
2 wherein said cellulose derivative is a mixture of
hydroxypropylcellulose and ethyl cellulose.
4. A sustained release dosage formulation of claim
1 wherein said polyvinylpyrrolidone has a molecular
weight of about 40,000.
5. A sustained release dosage formulation of claim
1 wherein said seed is sugar having a mesh of 60/80.

Description

HC~-18487A-CA


SUSTAINED RELEASE THEOPHYLLINE
A zero order release theophylline product, THEO-DUR,
has received widespread acceptance in the marketplace and
among the medical profession as a broncho-dilator. It is
desired to provide a sustained release broncho-dilator
which is in a form more suitable for administration to
children and the elderly.
In accordance with the present invention there are
provided micropellets of sustained release theophylline
which are designed for administration to children or the
elderly who may have difficulty swallowing a relatively
large table. The micropellets are provided in a capsule
as the dosage unit form, each capsule containing about
1000 microparticles or less to yield the total desired
dosage. For example, in one embodiment, a 100 mg dosage
of theophylline is provided with 845 microparticles.
The microparticles are provided by coating theo-
phylline in micronized form onto a sugar seed having
60/80 mesh with polyvinylpryrrolidone having a molecular
weight of from about 30,000 to about 50,000, with a
molecular weight of about 40,000 being a preferred
embodiment ("Kollidon~30"). A sustained release coating
is provided of cellulose derivatives. In a preferre
embodiment a mixture of ethylcellulose ~Dow, "E~oce
N-10") and hydroxypropylcellulose (Hercules, "Kluce ~ F")
is used. The average diameter of each particle is
roughly about 0.6mm.
The following example illustrates the invention:
EXAMPLE
3.2 kg polyvinylpyrrolidone (mw 40,000, Kollidon~ 0)
is dissolved in 32 1 isopropanol. Therein there is dis-
persed 12.8 kg of micronized theophylline. Into a Glatt~
column (six inch, Glatt CPCG) there is charged 4.0 kg




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sugar, 60/80 mesh. AFter the air suspension system is in
operation with the sugar, the dispersed theophylline is
charged into the Glatt column with the inlet air having a
temperature of 60C and the spray pressure at 4 bars, and
the spray rate being 100 ml/min.
After completion of the above procedure, the Glatt
column is stopped, and the product reserved as "Theo-
phylline pellets, Active I".
A second batch of 3.2 kg polyvinylpyrrolidone (mw
40,000, Kollidon 30) is dissolved into 32.0 1 isopro-
panol, and dispersed into the resultant mixture is 12.8
kg micronized theophylline. 4.0 kg of Theophylline
pellets, Active I are then charged into the same Glatt
column under the same conditions of temperature, pressure
and rate. The second batch having the theophylline
dispersed therein is then charged into the Glatt column
to further build up the coating.
The Glatt column is emptied and the product
labelled "Theophylline pettets, Active II".
A mixture of 13.2 l chloroform and 3.3 1 methanol is
prepared, into which are dispersed 992.0 g ethylcellulose
(Ethocel N-10, Dow) and 329.0 g hydroxypropyl cellulose
(Hercules, Klucel LF)/ Into the Glatt column is charged
19.0 kg of Theophylline pellets, Active II, which are
then coated with the coating mixture under conditions of
30C, spray pressure 3 bars and spray rate 100 ml/min.
The resultant coated pellets are small white micropellets
which to make up a dosage unit of 100 mg used 845 of such
micropellets which are placed into capsules for con-
venience. For a child or an elderly patient, the micro-
particles are typically sprinkled into food which is then
taken as part of a meal, to provide the sustained theo-
phylline effect.