[0001] The present disclosure relates to the field of pharmaceuticals for pediatrics. In
particular, the present disclosure relates to an oral dispersible film composition comprising
zinc salt for pediatric diarrhea, process of preparing the oral dispersible film from the oral
dispersible film composition and the oral dispersible film.
BACKGROUND OF THE INVENTION
[0002] Diarrhea is a condition where the patient has loose runny stools multiple times a day.
It is a fairly common condition affecting about everyone at least once in their lifetime. The
reasons for diarrhea may be several, including bacteria, viruses or parasites from stale food or
water, intolerance to certain foods, digestive or colon disorders, surgery etc. Generally it is
considered harmless however prolonged diarrhea must be checked by a doctor.
[0003] Children are frequently prone to diarrhea because of their sensitive digestive systems.
In fact, diarrhea is a leading cause for infant mortality, especially so in developing countries.
Care must be taken to provide the right medication and hydration to kids within time without
unnecessarily prolonging the treatment. Oral rehydration solutions (ORS) prevent or treat
dehydration and malnutrition in the body due to diarrhea. In ORS, water is supplemented
with specific amounts of sugar and salt that helps replace lost nutrients in the child.
[0004] Zinc supplementation along with oral rehydration solution is a well established and
recommended treatment in the management of pediatric diarrhea. Zinc is a vital nutrient that
has an effective mechanism of action in the gastrointestinal system including production of
antibodies, protein synthesis etc. It is recommended that a child 1-5 months of age should
receive 10mg of zinc per day for 10-14 days, and children 6-59 months of age should receive
20mg of zinc per day for 10-14 days. This treatment is given by care takers to the children,
mostly within their houses.
[0005] Several ways of providing zinc supplements have been known in the past. Dispersible
tablets, solutions, and suspensions are available but all these products have shown poor
acceptability by kids. Dispersible tablets need to be dispersed in breast milk or water for
administration. With oral solutions and suspensions there is difficultly to maintain dose
uniformity.
[0006] There is an unmet need in the art to provide zinc supplementation, which is easy to
use, suitable for kids and economical.
3
OBJECTS OF THE INVENTION
[0007] An object of the present invention is to provide oral dispersible films.
[0008] An object of the present invention is to provide an oral dispersible film comprising
zinc that is suitable for treating pediatric diarrhea.
[0009] An object of the present invention is to provide an oral dispersible film comprising
zinc that is easily administered to kids.
[00010] An object of the present invention is to provide an oral dispersible film comprising
zinc that has dose uniformity.
[00011] An object of the present invention is to provide an oral dispersible film comprising
zinc with low disintegrating time.
[00012] An object of the present invention is to provide an oral dispersible film that is
available at an affordable price.
[00013] An object of the present invention is to provide a one-step process for preparing an
oral dispersible film comprising zinc.
SUMMARY
[00014] In an aspect, the present invention relates to a composition for an oral dispersible
film comprising zinc salt for treatment of pediatric diarrhea.
[00015] In an aspect, the present invention relates to an oral dispersible film composition for
pediatric diarrhea comprising: a pharmaceutically acceptable salt of zinc in therapeutically
effective amount; a hydrophilic film forming polymer; a plasticizer; a disintegrating agent; a
taste masking agent and a solvent.
[00016] In an embodiment, the present disclosure provides an oral dispersible film
composition for pediatric diarrhea comprising: a pharmaceutically acceptable salt of zinc in
therapeutically effective amount of from about 50 mg to about 150 mg by weight; a
hydrophilic film forming polymer in an amount from about 50 mg to about 150 mg by
weight; a plasticizer in an amount from about 0.1 ml to 0.3 ml by volume; a disintegrating
agent in an amount from about 25 mg to about 75 mg by weight; and a taste masking agent in
an amount from 15 mg to about 40 mg by weight.
[00017] In an aspect, the present invention relates to a process for preparing an oral
dispersible film from an oral dispersible film composition comprising zinc salt.
[00018] In an aspect, the present invention relates to an oral dispersible film obtained by the
process of solvent casting method.
4
[00019] These and other features, aspects, and advantages of the present subject matter will
be better understood with reference to the following description and appended claims. This
summary is provided to introduce a selection of concepts in a simplified form. This summary
is not intended to identify key features or essential features of the claimed subject matter, nor
is it intended to be used to limit the scope of the claimed subject matter.
BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS
[00020] The following drawings form part of the present specification and are included to
further illustrate aspects of the present disclosure. The disclosure may be better understood by
reference to the drawings in combination with the detailed description of the specific
embodiments presented herein.
[00021] Figure 1 depicts a sample of the oral dispersing film in accordance with an
embodiment of the invention.
DETAILED DESCRIPTION OF THE INVENTION
[00022] Those skilled in the art will be aware that the present disclosure is subject to
variations and modifications other than those specifically described. It is to be understood
that the present disclosure includes all such variations and modifications. The disclosure also
includes all such steps, features, compositions and compounds referred to or indicated in this
specification, individually or collectively, and any and all combinations of any or more of
such steps or features.
[00023] Unless/ the context requires otherwise, throughout the specification which follow,
the word “comprise” and variations thereof, such as, “comprises” and “comprising” are to be
construed in an open, inclusive sense that is as “including, but not limited to.”
[00024] Reference throughout this specification to “one embodiment” or “an embodiment”
means that a particular feature, structure or characteristic described in connection with the
embodiment is included in at least one embodiment. Thus, the appearances of the phrases “in
one embodiment” or “in an embodiment” in various places throughout this specification are
not necessarily all referring to the same embodiment. Furthermore, the particular features,
structures, or characteristics may be combined in any suitable manner in one or more
embodiments.
[00025] As used in the description herein and throughout the claims that follow, the
meaning of “a,” “an,” and “the” includes plural reference unless the context clearly dictates
5
otherwise. Also, as used in the description herein, the meaning of “in” includes “in” and “on”
unless the context clearly dictates otherwise.
[00026] In some embodiments, the numbers expressing quantities of ingredients, properties
such as concentration, and so forth, used to describe and claim certain embodiments of the
invention are to be understood as being modified in some instances by the term “about.”
Accordingly, in some embodiments, the numerical parameters set forth in the written
description are approximations that can vary depending upon the desired properties sought to
be obtained by a particular embodiment. In some embodiments, the numerical parameters
should be construed in light of the number of reported significant digits and by applying
ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters
setting forth the broad scope of some embodiments of the invention are approximations, the
numerical values set forth in the specific examples are reported as precisely as practicable. In
some embodiment, the term “about” means + 10.
[00027] The recitation of ranges of values herein is merely intended to serve as a shorthand
method of referring individually to each separate value falling within the range. Unless
otherwise indicated herein, each individual value is incorporated into the specification as if it
were individually recited herein.
[00028] Groupings of alternative elements or embodiments of the invention disclosed herein
are not to be construed as limitations. Each group member can be referred to and claimed
individually or in any combination with other members of the group or other elements found
herein. One or more members of a group can be included in, or deleted from, a group for
reasons of convenience and/or patentability.
[00029] All methods described herein can be performed in suitable order unless otherwise
indicated herein or otherwise clearly contradicted by context. The use of any and all
examples, or exemplary language (e.g. “such as”) provided with respect to certain
embodiments herein is intended merely to better illuminate the invention and does not pose a
limitation on the scope of the invention otherwise claimed. No language in the specification
should be construed as indicating any non-claimed element essential to the practice of the
invention.
[00030] All publications herein are incorporated by reference to the same extent as if each
individual publication or patent application were specifically and individually indicated to be
incorporated by reference. Where a definition or use of a term in an incorporated reference is
inconsistent or contrary to the definition of that term provided herein, the definition of that
term provided herein applies and the definition of that term in the reference does not apply.
6
[00031] The headings and abstract of the invention provided herein are for convenience
only and do not interpret the scope or meaning of the embodiments.
[00032] Various terms are used herein. To the extent a term used in a claim is not defined
below, it should be given the broadest definition persons in the pertinent art have given that
term as reflected in printed publications and issued patents at the time of filing.
[00033] In an embodiment, the present invention relates to an oral dispersible film
composition for pediatric diarrhea comprising a zinc salt.
[00034] In an embodiment, the present invention relates to an oral dispersible film
composition for pediatric diarrhea comprising: a pharmaceutically acceptable salt of zinc in
therapeutically effective amount; a hydrophilic film forming polymer; a plasticizer; a
disintegrating agent; a taste masking agent and a solvent.
[00035] In an embodiment, the present disclosure provides an oral dispersible film
composition for pediatric diarrhea comprising: a pharmaceutically acceptable salt of zinc in
therapeutically effective amount of from about 50 mg to about 150 mg by weight; a
hydrophilic film forming polymer in an amount from about 50 mg to about 150 mg by
weight; a plasticizer in an amount from about 0.1 ml to 0.3 ml by volume; a disintegrating
agent in an amount from about 25 mg to about 75 mg by weight; and a taste masking agent in
an amount from 15 mg to about 40 mg by weight.
[00036] In an embodiment, the present invention relates to an oral dispersible film
composition for pediatric diarrhea wherein the zinc salt is selected from the group consisting
of zinc sulphate, zinc acetate, zinc gluconate and the like.
[00037] In an embodiment, the present invention relates to an oral dispersible film
composition for pediatric diarrhea wherein the zinc salt is the active agent.
[00038] In an embodiment, the zinc salt is present in a range of about 75mg to about 125mg
by weight.
[00039] In an embodiment, the zinc salt is present in a range of about 90 mg to about 110
mg by weight.
[00040] In an embodiment, the hydrophilic film forming polymer is cellulose based
hydrophilic polymer having low viscosity of about 3 cPs to about 6 cPs.
[00041] In an embodiment, the cellulose based hydrophilic polymer having low viscosity is
selected from hydroxypropyl methylcellulose (HPMC), HPMC E-15, hydroxyl propyl
cellulose (HPC), hydroxyethyl cellulose (HEC) and carboxymethylcellulose (CMC).
7
[00042] In an embodiment, the hydroxypropyl methylcellulose is selected from the group
consisting of hydroxypropyl methylcellulose E3, hydroxypropyl methylcellulose E5 and
hydroxypropyl methylcellulose E6.
[00043] In an embodiment, the hydrophilic film forming polymer is present in an amount
ranging from about 75 mg to about 125 mg.
[00044] In an embodiment, the hydrophilic film forming polymer is present in an amount
ranging from about 90 mg to about 110 mg.
[00045] In an embodiment, the plasticizer is selected from the group consisting of
polyethylene glycol (PEG), propylene glycol, sorbitol and glycerine.
[00046] In an embodiment, the polyethylene glycol is selected from the group comprising
PEG-200 and PEG-400.
[00047] In an embodiment, the polyethylene glycol is present in the range of about 0.14 ml
to about 0.20 ml.
[00048] In an embodiment, the present invention the disintegrating agent is selected from the
group consisting of microcrystalline cellulose, sodium starch glycolate, crosspovidone and
starch.
[00049] In an embodiment, the microcrystalline cellulose is of the type having median
particle size of 100 microns.
[00050] In an embodiment, the microcrystalline cellulose is selected from the group
consisting of Avicel PH 102, PH 101 and the like.
[00051] In an embodiment, the microcrystalline cellulose is present in an amount from about
45 mg to about 55 mg by weight.
[00052] In an embodiment, the disintegrating agent also acts as a diluent.
[00053] In an embodiment, the oral dispersible film composition for pediatric diarrhea
further comprises a diluent.
[00054] In an embodiment, the taste masking agent is selected from the group consisting of
mannitol, sucrose, glucose, maltose, maltodextrin, sodium saccharin, fructose and the like.
[00055] In an embodiment, the taste masking agent is responsible for masking the metallic
taste of zinc.
[00056] In an embodiment, the taste masking agent also acts as sweetener.
[00057] In an embodiment, the taste masking agent enhances the feel of the oral dispersible
film in the mouth.
[00058] In an embodiment, the taste masking agent is present in a range of about 20 mg to
about 30 mg by weight.
8
[00059] In an embodiment, the present invention relates to an oral dispersible film
composition for pediatric diarrhea further comprising a solvent.
[00060] In an embodiment, the present invention relates to an oral dispersible film
composition for pediatric diarrhea wherein the solvent is selected from water, methanol, and
ethanol.
[00061] In an embodiment, the solvent is present in an amount from about 10 ml to about 15
ml by volume.
[00062] In an embodiment, the present disclosure provides an oral dispersible film
composition for pediatric diarrhea comprising: zinc sulphate from about 75 mg to about 125
mg by weight; hydroxypropyl methylcellulose having viscosity of about 3 cPs to about 6 cPs
in an amount from about 75 mg to about 125 mg by weight; PEG-200 from about 0.15 ml to
about 0.2 ml by volume; microcrystalline cellulose having median particle size of about 100
micron in an amount from about 35 mg to about 65 mg by weight; mannitol from about 15
mg to about 35 mg by weight; and water from about 10 ml to about 20 ml.
[00063] In an embodiment, the present invention provides an oral dispersible film prepared
from the oral dispersible film composition in accordance with the present disclosure.
[00064] In an embodiment, the present invention relates to the process of preparing the oral
dispersible film in a one-step process.
[00065] In an embodiment, the present invention relates to the process of preparing the oral
dispersible film wherein the process uses solvent casting method.
[00066] In an embodiment of the present invention, wherein the process of preparing the oral
dispersible film involves the following:
a. mixing of all the components of the oral dispersible film composition;
b. spreading the composition on a suitable surface( plastic petri plate); and
c. letting the solvent evaporate at 40º-50ºC thereby forming an oral
dispersible film; and
d. removing it from plate and cutting into 2x2 cm.
[00067] In an embodiment, the present invention relates to an oral dispersible film prepared
by the solvent casting method. In this all ingredients along with the zinc sulfate are dissolved
in approximately 10-12 ml of water and stirred for 5 minutes to get homogenous solution and
thickness is kept up to 0.7 inches as uniform distribution of zinc sulfate dissolution of film in
oral cavity depends on thickness.
[00068] In an embodiment, the present invention relates to an oral dispersible film having
disintegration time in the range of about 40 to about 50 seconds.
9
[00069] In an embodiment, the present invention relates to an oral dispersible film having
thickness in the range of about 20mm to about 25mm.
[00070] In an embodiment, the present invention relates to an oral dispersible film wherein
the content of the active ingredient is in the range of about 98 to about 99.8%.
[00071] In an embodiment, the present invention relates to an oral dispersible film having
folding endurance in the range of about 200 to about 300.
[00072] In an embodiment, the present invention relates to an oral dispersible film for
pediatric diarrhea prepared by the solvent casting method.
[00073] In an embodiment, the present invention relates to an oral dispersible film wherein
the strong taste of metallic zinc is masked.
[00074] In an embodiment, the present invention relates to an oral dispersible film wherein
the film offers a high degree of patient compliance.
[00075] In an embodiment, the present invention relates to an oral dispersible film wherein
the film is easy to administer to kids.
[00076] In an embodiment, the present invention relates to an oral dispersible film which can
be administered to kids at home by care givers.
[00077] In an embodiment, the present invention relates to an oral dispersible film wherein
the film dissolves easily by placing in the mouth without breast milk or water.
[00078] In an embodiment, the present invention relates to an oral dispersible film that has
dose uniformity.
[00079] In an embodiment, the present invention relates to an oral dispersible film that has
high folding endurance.
[00080] In an embodiment, the present invention relates to an oral dispersible film wherein
the composition is economical.
[00081] The inventors of the present invention are capable of overcoming the deficiencies of
the existing art by providing the unique oral dispersible film comprising zinc sulphate.
[00082] While the foregoing describes various embodiments of the disclosure, other and
further embodiments of the disclosure may be devised without departing from the basic scope
thereof. The scope of the invention is determined by the claims that follow. The invention is
not limited to the described embodiments, versions or examples, which are included to enable
a person having ordinary skill in the art to make and use the invention when combined with
information and knowledge available to the person having ordinary skill in the art.
[00083] The foregoing embodiments are merely illustrative and are not to be taken as
limitations upon the scope of the invention. Various changes and modifications to the
10
disclosed embodiments will be apparent to those skilled in the art. Such changes and
modifications may be made without departing from the scope of the invention.
[00084] The present invention is further explained in the form of following examples.
However, it is to be understood that the following examples are merely illustrative and are
not to be taken as limitations upon the scope of the invention.
Example 1
Oral dispersible film composition and preparation of an oral strip of zinc sulphate
[00085] The composition for preparing an oral dispersible film comprised of the following
components as per Table 1:
Table 1: composition of orally disintegrating film
Ingredients Quantity taken(mg/mL) Function
HPMC-E5 100 mg As a film former
Zinc sulfate 100 mg Active ingredient
Mannitol 25 mg
Enhance mouth feel and mask the
metallic taste of zinc
Avicel PH 102 50 mg
As a diluents and disintegrating
agent
PEG- 200 0.18 mL Plasticizer
Water 12mL Solvent
Process of preparing the oral dispersible film as per Table 1:
[00086] The contents of Table 1 were mixed in a suitable container along with water and
poured for casting on a petriplate of area 64.19 cm2
. The solvent was allowed to evaporate at
40-50ºC leaving behind the oral dispersible thin film comprising zinc sulphate. A total of 10
films each of size 2*2 cm2 were obtained from 64.19 cm2
larger batch.
[00087] Disintegration time was estimated to measure the time taken by the film to dissolve
within mouth in order to produce action. Disintegration time was noted by dispersing the film
of sample size 2x2 cm2
in 10ml of phosphate buffer pH 6.8 and time for complete
disintegration was noted down.
[00088] Weight and thickness were measured to check uniformity in each sample. Weight of
each film was taken using electronic balance. Uniformity in thickness was measured using
vernier caliper.
11
[00089] Drug content was estimated to ensure the uniformity in distribution of zinc sulfate
throughout the film. To ensure uniformity in distribution of zinc sulfate, drug content was
measured by dissolving the film in phosphate buffer pH 6.8 and absorbance of resulting
solution was measured using UV spectrophotometer.
[00090] Folding endurance ensure the flexibility in handling. Folding endurance was
measured manually by repeatedly folding the film from the same point to check the flexibility
of film and breaking strength.
[00091] Characterization of each of the films was performed and the results obtained were
noted below in Table 2:
Table 2: Characteristic of oral disintegrating strip of zinc sulphate
Parameter Value
Disintegrating time 50 seconds
Weight 60 mg
Thickness 25 mm
Drug content 99.9%
Folding endurance 300
[00092] The foregoing examples are merely illustrative and are not to be taken as limitations
upon the scope of the invention. Various changes and modifications to the disclosed
embodiments will be apparent to those skilled in the art. Such changes and modifications may
be made without departing from the scope of the invention.
ADVANTAGES OF THE PRESENT INVENTION
[00093] The present invention provides an oral dispersible film comprising zinc salt for the
treatment of pediatric diarrhea, wherein the oral dispersible film has high patient compliance.
[00094] The present invention provides an oral dispersible film wherein the film is less bulky
compared to dispersible tablets.
[00095] The present invention provides an oral dispersible film that has fast action in the
mouth.
[00096] The present invention provides an oral dispersible film that has high folding
endurance.
12
[00097] The present invention provides an oral dispersible film that has dose uniformity.

We Claim:
1. An oral dispersible film composition for pediatric diarrhea comprising:
a pharmaceutically acceptable salt of zinc in therapeutically effective amount of from
about 50 mg to about 150 mg by weight; a hydrophilic film forming polymer in an
amount from about 50 mg to about 150 mg by weight; a plasticizer in an amount from
about 0.1 ml to 0.3 ml by volume; a disintegrating agent in an amount from about 25
mg to about 75 mg by weight; and a taste masking agent in an amount from 15 mg to
about 40 mg by weight.
2. The oral dispersible film composition as claimed in claim 1, wherein the zinc salt is
selected from the group consisting of zinc sulphate, zinc actetate and zinc gluconate.
3. The oral dispersible film composition as claimed in claim 1, wherein the hydrophilic
film forming polymer is cellulose based hydrophilic polymer having low viscosity of
about 3 cPs to about 6 cPs.
4. The oral dispersible film composition as claimed in claim 3, wherein the hydrophilic
film forming cellulose based hydrophilic polymer of low viscosity is selected from
hydroxypropyl methylcellulose (HPMC), hydroxyethylcellulose (HEC),
hydroxyethylcelluose (HPC) and carboxymethylcellulose(CMC).
5. The oral dispersible film composition as claimed in claim 4, wherein the
hydroxypropyl methylcellulose is selected from the group consisting of
hydroxypropyl methylcellulose E3, hydroxypropyl methylcellulose E5, and
hydroxypropyl methylcellulose E6.
6. The oral dispersible film composition as claimed in claim 1, wherein the plasticizer is
selected from the group consisting of polyethylene glycol, propylene glycol, glycerine
and sorbitol.
7. The oral dispersible film composition as claimed in claim 6, wherein the polyethylene
glycol is selected from the group consisting of PEG-200 and PEG-400.
8. The oral dispersible film composition as claimed in claim 1, wherein the
disintegrating agent is selected from the group consisting of microcrystalline
cellulose, sodium starch glycolate, starch and crosspovidone.
9. The oral dispersible film composition as claimed in claim 8, wherein the
microcrystalline cellulose is the type having median particle size of 100 microns.
14
10. The oral dispersible film composition as claimed in claim 1, wherein the taste
masking agent is selected from the group consisting of mannitol, sucrose, maltose,
fructose, maltodextrin, sodium saccharin and glucose.
11. The oral dispersible film composition for pediatric diarrhea as claimed in claim 1,
wherein the composition further comprises a solvent selected from the group
consisting of water, ethanol and methanol.
12. A process for preparing an oral dispersible film from the oral dispersible film
composition as claimed in claim 1, the process comprising the steps of:
a. mixing of all the components of the oral dispersible film composition;
b. spreading the composition on a suitable surface; and
c. letting the solvent evaporate thereby forming an oral dispersible film.
13. An oral dispersible film obtained by the process as claimed in the claim 12, wherein
the film has a disintegration time of 40 to 50 seconds.
14. The oral dispersible film obtained by the process as claimed in the claim 12, wherein
the film has a folding endurance of 200 to 300.
15. The oral dispersible film obtained by the process as claimed in the claim 12, wherein
the film has a thickness of 20mm to 25mm.