HIGH-CONTENT FAMCICLOVIR TABLETS

COMPRIMES A FORTE TENEUR EN FAMCICLOVIR

English Abstract

A pharmaceutical tablet wherein famciclovir is the active ingredient and
wherein the percentage of famciclovir by weight in the tablet
is 85% or greater.

French Abstract

On décrit un comprimé pharmaceutique dans lequel le famciclovir constitue le principe actif et le pourcentage pondéral du famciclovir représente au moins 85 % du poids du comprimé.

Claims

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CLAIMS:

1. A pharmaceutical tablet wherein famciclovir is the
active ingredient and wherein the percentage of famciclovir
by weight in the tablet is 85% or greater and the percentage
of excipient by weight in the tablet is 15% or less.

2. A pharmaceutical tablet according to claim 1,
wherein the excipient comprises lactose in an amount of less
than 15% based on weight of the tablet.

3. A pharmaceutical tablet according to claim 1,
wherein the excipient comprises lactose in an amount of less
than 5% based on weight of the tablet.

4. A pharmaceutical tablet according to claim 1,
wherein the excipient is free of lactose.

5. A pharmaceutical tablet according to claim 1,
wherein the percentage of famciclovir by weight in the
tablet is 90% or greater and the percentage of excipient by
weight in the tablet is 10% or less.

6. A pharmaceutical composition according to claim 5,
wherein the excipient is lactose in an amount of less than
10%, based on weight of the tablet.

7. A pharmaceutical composition according to claim 5,
wherein the excipient is lactose in an amount of less than
5%, based on weight of the tablet.

8. A pharmaceutical tablet according to claim 5,
wherein the excipient is free of lactose.

9. A pharmaceutical tablet according to any one of
claims 1 to 8, having the following composition:


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Constituent %w/w

Famciclovir 91.42
Hydroxypropyl cellulose 2.83
Sodium starch glycollate 5.00
Magnesium stearate 0.75
Anyhdrous lactose 0.

10. A pharmaceutical tablet according to any one of
claims 1 to 9, containing 500 mg or 750 mg of famciclovir.

11. A process for the preparation of a tablet
according to any one of claims 1 to 10, wherein the
famciclovir and excipients are granulated and then
compressed to form a tablet.

12. A process according to claim 11, wherein the
famciclovir is granulated with hydroxypropyl cellulose,
blended with any further excipients and then compressed to
form a tablet.

Description

CA 02240462 2005-06-O1
21489-9686(S)
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HIGH-CONTENT FAMCICLOVIR TABLETS
This invention relates to a novel formulation of a pharmaceutical
product.
EP-A-182024 (Beecham Group p.l.c.), Example 2 describes a method of the
preparation of famciclovir, a compound which is useful as the oral form of the
compound, penciclovir which has andviral activity against infections caused by
herpesviruses, such as herpes simplex type 1, herpes simplex type 2 and
varicella
zost~~r virus, and also against Hepatitis B virus. Penciclovir and its
antiviral activity is
disclosed in Abstract P.V 11-5 p.193 of 'Abstracts of 14th Int. Congress of
Microbiology', Manchester, England 7-13 September 1986 (Boyd et. al.).
Famciclovir is preferably administered in the form of tablets containing
125 mg, 250 mg, 500 mg or 750 mg of active ingredient. As is conventional in
tablet
compositions, the tablets contain excipients such as lactose, sodium starch
glycollate
and :magnesium stearate such that the total excipient content is at least 15%.
Anhydrous lactose is conventionally included as a major excipient to
compensate for
any ~~otential inconsistencies in the compression properties of the active
ingredient.
The higher the percentage excipient content, the greater the tablet size for a
tablet of any given dosage. Particularly in the case of tablets containing 500
mg and
750 mg of active ingredient, the large tablet size can affect patient
compliance as the
oval face of the tablet would measure 18mm x 8.Smm and 21 mm x l Omm
respf;ctively when the tablet contains about 76% famciclovir.
It has been discovered that it is possible to formulate famciclovir into a
tablet
containing less than 15% excipients as the compression properties of
famciclovir have
proved to be sufficiently consistent to permit this.
Accordingly, the present invention provides a pharmaceutical tablet wherein
famciclovir is the active ingredient and wherein the percentage of famciclovir
by
weight in the tablet is 85% or greater.

CA 02240462 2005-06-O1
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According to one aspect of the present invention,
there is provided a pharmaceutical tablet wherein
famciclovir is the active ingredient and wherein the
percentage of famciclovir by weight in the tablet is 85% or
greater and the percentage of excipient by weight in the
tablet is 150 or less.
According to another aspect of the present
invention, there is provided a process for the preparation
of a tablet as described herein, wherein the famciclovir and
excipients are granulated and then compressed to form a
tablet.
All values for percentage weight given herein
unless otherwise stated are defined in terms of the core of
any tablet which may be coated, for example, film coated.


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A suitable tablet contains less than 15%, less than 10%, less than 5% and
preferably 0% of anhydrous lactose or other similar excipient such as
microcrystalline
cellulose.
A suitable tablet contains famciclovir at a percentage Weight of greater than
85%, 86%, 87%, 88%, 89%, 90% or 91%. The highest possible percentage of
famciclovir is preferred. Famciclovir may be in any suitable pharmaceutically
acceptable form, such as in the forni of a salt, solvate or polymorph.
Famciclovir is
preferably in an anhydrous, free base form.
Conventional excipients included in the composition of the tablet include
IO hydroxypropyl cellulose, for example up to 5% or up to 3%, sodium starch
glycollate,
for example up to 15%, 10%, 7% or 5% and magnesium stearate, for example up to
2% or 1%.
The tablets may be coated with any suitable coating used for pharmaceutical
tablets.
The tablets may be prepared by conventional compression methods known in
the art. In a preferred method, famciclovir is granulated with an excipient
such as
hydroxypropyl cellulose, in order to minimise the effect of any variations in
physical
form of the active ingredient. The granules are screened and dried and then
blended
with any further excipients to form a compression mix. Tablets are compressed
to the
size and weight appropriate to the required dosage and then optionally coated
as
desired.
The following Example illustrates the invention.


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EXAMPLE
The percentage values in brackets indicate the percentage values in the
famciclovir
tablets currently registered by the regulatory authorities for
pharmaceuticals, in the
United Kingdom of Great Britain and Northern Ireland, the U.S.A and other
countries
of the world.
Constituent %w/w %w/w


Famciclovir 91.42 (75.66)


Hydroxypropyl cellulose2.83 (2.34)


sodium starch glycollate5.00 (5.00)


magnesium stearate 0.75 (0.75)


anhydrous lactose 0 ( 16.25)


Approximate Core Weight is 547mg for 500mg dosage and 820mg for 750mg
dosage.
For coated tablets, 2.5% of core weight is added by the coating and the coated
tablet weighs 560mg for the 500mg dosage and 840mg for the 750mg dosage.
The tablets are prepared by dry mixing famciclovir with hydroxypropyl
cellulose and then granulating the mixture with water in a high shear
granulator. The
wet mass is screened, dried and milled. The milled granules are blended with
sodium
starch glycollate and magnesium stearate to produce the compression mix.
Tablets are
compressed at the size and weight appropriate to the required strength of
tablet and
then aqueous film coated.
The resulting size of an oval face of a 750mg tablet is l9mm x 9mm and of a
500mg tablet is l7mm x 8mm.