DESC:The following specification describes particularly the invention and in the manner in
which it is to be performed:
2
FIELD OF THE INVENTION
The present application relates to solid state forms of Viloxazine hydrochloride
and processes for preparation thereof.
The drug compound having the adopted name “Viloxazine hydrochloride”,
chemically designated as 2-[(2-ethoxyphenoxy)methyl]morpholine hydrochloride and is
represented by structure of Formula I.
Formula I
Viloxazine hydrochloride is indicated for major depressive disorder and for the
treatment of patients with attention deficit hyperactivity disorder (ADHD).
U.S. Patent No. 3, 714, 161 discloses Viloxazine hydrochloride and process for
its preparation.
U.S. Patent No. 10, 160, 733 discloses Viloxazine hydrochloride crystalline
Form-A, Form-B and process for preparation thereof.
Crystalline solids normally require a significant amount of energy for dissolution
due to their highly organized, lattice like structures. For example, the energy required for
a drug molecule to escape from a crystal is more than from an amorphous or a noncrystalline
form. It is known that the amorphous forms in a number of drugs exhibit
different dissolution characteristics and in some cases different bioavailability patterns
compared to the crystalline form. For some therapeutic indications, one bioavailability
pattern may be favored over another. Therefore, it is desirable to have amorphous forms
of drugs with high purity to meet the needs of regulatory agencies and also highly
reproducible processes for their preparation.
3
In view of the above, it is therefore, desirable to prepare a stable amorphous
form of Viloxazine hydrochloride. The amorphous form provided herein is a free
flowing powder.
Amorphous solid dispersions of drugs are generally known to improve the
stability and solubility of drug products. However, such dispersions are generally
unstable over time. Amorphous solid dispersions of drugs tend to convert to crystalline
forms over time, which can lead to improper dosing due to differences of the solubility
of crystalline drug material compared to amorphous drug material. The present
invention, however provides stable amorphous solid dispersions of Viloxazine
hydrochloride. Moreover, the present invention provides solid dispersions of Viloxazine
hydrochloride which may be reproduced easily and is amenable for processing into a
dosage form.
SUMMARY OF THE INVENTION
In the first embodiment, the present application provides a pharmaceutical
composition comprising amorphous form of Viloxazine hydrochloride and one or more
pharmaceutically acceptable excipients.
In the second embodiment, the present application provides a solid dispersion
comprising amorphous form of Viloxazine hydrochloride and one or more
pharmaceutically acceptable carriers.
In the third embodiment, the present application provides a method for preparing
a solid dispersion comprising amorphous Viloxazine hydrochloride and one or more
pharmaceutically acceptable carriers comprising the steps of:
a) providing a mixture of Viloxazine hydrochloride and one or more
pharmaceutically acceptable carriers in a solvent; and
b) isolating solid dispersion comprising amorphous Viloxazine hydrochloride
and one or more pharmaceutically acceptable carriers.
In the fourth embodiment, the present application provides a method for
preparing a solid dispersion comprising amorphous Viloxazine hydrochloride and one or
more pharmaceutically acceptable carriers comprising the steps of:
4
a) physically blending Viloxazine hydrochloride and one or more
pharmaceutically acceptable carriers; and
b) isolating solid dispersion comprising amorphous Viloxazine hydrochloride
and one or more pharmaceutically acceptable carriers.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is an illustration of powder X-ray diffraction (“PXRD”) pattern of Viloxazine
hydrochloride present in amorphous solid dispersion according to example 1.
FIG. 2 is an illustration of powder X-ray diffraction (“PXRD”) pattern of Viloxazine
hydrochloride present in amorphous solid dispersion according to example 2.
FIG. 3 is an illustration of powder X-ray diffraction (“PXRD”) pattern of Viloxazine
hydrochloride present in amorphous solid dispersion according to example 3.
FIG. 4 is an illustration of powder X-ray diffraction (“PXRD”) pattern of Viloxazine
hydrochloride present in amorphous solid dispersion according to example 4
DESCRIPTION OF THE INVENTION
In the first embodiment, the present application provides a pharmaceutical
composition comprising amorphous form of Viloxazine hydrochloride and one or more
pharmaceutically acceptable excipients.
In an aspect, the said amorphous form of Viloxazine hydrochloride may be
formulated as: solid oral dosage forms such as, but not limited to, powders, granules,
pellets, tablets, and capsules; liquid oral dosage forms such as, but not limited to, syrups,
suspensions, dispersions, and emulsions; and injectable preparations such as, but not
limited to, solutions, dispersions, and freeze dried compositions. Formulations may be
in the form of immediate release, delayed release, or modified release. Further,
immediate release compositions may be conventional, dispersible, chewable, mouth
dissolving, or flash melt preparations, and modified release compositions that may
comprise hydrophilic or hydrophobic, or combinations of hydrophilic and hydrophobic,
release rate controlling substances to form matrix or reservoir or combination of matrix
5
and reservoir systems. The compositions may be prepared using any one or more of
techniques such as direct blending, dry granulation, wet granulation, and extrusion and
spheronization. Compositions may be presented as uncoated, film coated, sugar coated,
powder coated, enteric coated, and modified release coated.
In the second embodiment, the present application provides a solid dispersion
comprising amorphous form of Viloxazine hydrochloride and one or more
pharmaceutically acceptable carriers.
Solid dispersion as used herein refers to the dispersion of one or more active
ingredients in an inert excipient or polymer or carrier, where the active ingredients could
exist in finely crystalline, solubilized or amorphous state (Sareen et al., 2012 and Kapoor
et al., 2012). Solid dispersion consists of two or more components, generally a polymer
or carrier and drug optionally along with stabilizing agent (and/or surfactant or other
additives). The most important role of the added polymer or carrier or excipient in solid
dispersion is to reduce the molecular mobility of the drug to avoid the phase separation
and re-crystallization of drug during storage. The resulting solid dispersions may have
increased solubility. The increase in solubility of the drug in solid dispersion is mainly
because drug remains in amorphous form which is associated with a higher energy state
as compared to crystalline counterpart and due to that it requires very less external
energy to dissolve.
A solid dispersion is a molecular dispersion of a compound, particularly a drug
substance within a polymer or carrier. Formation of a molecular dispersion provides a
means of reducing the particle size to nearly molecular levels (i.e. there are no particles).
As the carrier dissolves, the drug is exposed to the dissolution media as fine particles
that are amorphous, which can dissolve and be absorbed more rapidly than larger
particles.
In general, the term "solid dispersion" refers to a system in a solid state
comprising at least two components, wherein one component is dispersed throughout the
other component or components. The term "solid dispersion" as used herein, refers to
stable solid dispersions comprising amorphous drug substance and one or more
6
polymers or carriers. Further the term "solid dispersion" as used herein also refers to
stable solid dispersions comprising amorphous drug substance and one or more
polymers or carriers with or without adsorbent/absorbent. By "amorphous drug
substance," it is meant that the amorphous solid contains drug substance in a
substantially amorphous solid state form i.e. at least about 80% of the drug substance in
the dispersion is in an amorphous form. More preferably at least about 90% and most
preferably at least about 95% of the drug substance in the dispersion is in amorphous
form.
The solid dispersion of Viloxazine hydrochloride of the present invention can be
made by any of the numerous methods that result in a solid dispersion comprising
amorphous Viloxazine hydrochloride. Several approaches can be used for the
preparation of solid dispersion which includes spray drying, lyophilization, fusion
method, solvent evaporation, hot-melt extrusion, ball milling, particle size reduction,
supercritical fluid (SCF) processes, kneading, inclusion complexes, electrostatic
spinning method, melt crystallization and surface-active carriers.
Viloxazine hydrochloride can be incorporated in the dispersion in amorphous
state.
The dispersing agent is typically composed of a pharmaceutically acceptable
substance that does not substantially interfere with the pharmaceutical action of
Viloxazine hydrochloride. The phrase "pharmaceutically acceptable" is employed herein
to refer to those substances which are, within the scope of sound medical judgment,
suitable for use in contact with the tissues of human beings and animals without
excessive toxicity, irritation, allergic response, or other problem or complication,
commensurate with a reasonable benefit/risk ratio. In some embodiments, the carrier is a
solid at room temperature.
Non-limiting examples of suitable polymers or carriers are celluloses (e.g.,
carboxymethylcelluloses, methylcelluloses, hydroxypropylcelluloses,
hydroxypropylmethylcelluloses); polysaccharides, heteropolysaccharides (pectins);
poloxamers; poloxamines; ethylene vinyl acetates; polyethylene glycols; dextrans;
7
polyvinylpyrrolidones; chitosans; polyvinylalcohols; propylene glycols;
polyvinylacetates; phosphatidylcholines (lecithins); miglyols; polylactic acid;
polyhydroxybutyric acid; mixtures of two or more thereof, copolymers thereof,
derivatives thereof, and the like. Further examples of carriers include copolymer systems
such as polyethylene glycol-polylactic acid (PEG-PLA), polyethylene glycolpolyhydroxybutyric
acid (PEG-PHB), polyvinylpyrrolidone-polyvinylalcohol (PVPPVA),
and derivatized copolymers such as copolymers of N-vinyl purine (or pyrimidine)
derivatives and N-vinylpyrrolidone.
An enteric coating polymer can also be used according to the present invention.
Specific examples of the enteric coating polymers include cellulose acetate phthalate,
cellulose acetate trimellitate, cellulose acetate succinate, hydroxymethylcellulose ethyl
phthalate, hydroxypropylmethylcellulose phthalate, eudragit,
hydroxypropylmethylcellulose acetate succinate, hydroxypropylmethyl acetate maleate,
hydroxypropylmethyl trimellitate, carboxymethylethylcellulose, polyvinyl butyrate
phthalate, polyvinyl alcohol acetate phthalate, methacrylic acid/ethyl acrylate
copolymer, and methacrylic acid/methyl methacrylate copolymer, hydroxypropyl
methylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate,
hydroxypropylmethyl acetate maleate and hydroxypropylmethyl trimellitate.
In the third embodiment, the present application provides a method for preparing
a solid dispersion comprising amorphous Viloxazine hydrochloride and one or more
pharmaceutically acceptable carriers comprising the steps of:
a) providing a mixture of Viloxazine hydrochloride and one or more
pharmaceutically acceptable carriers in a solvent; and
b) isolating solid dispersion comprising amorphous Viloxazine hydrochloride
and one or more pharmaceutically acceptable carriers.
Step (a) involves providing a mixture of Viloxazine hydrochloride and one or
more pharmaceutically acceptable carriers in a solvent;
Any physical form of Viloxazine hydrochloride may be utilized for providing the
mixture of Viloxazine hydrochloride in step (a).
8
Suitable pharmaceutically acceptable polymers or carriers that are dispersing
agents which can be used in step (a) include, but are not limited to: diluents such as
starches, pregelatinized starches, lactose, powdered celluloses, microcrystalline
celluloses, dicalcium phosphate, tricalcium phosphate, mannitol, sorbitol, sugar and the
like; binders such as acacia, guar gum, tragacanth, gelatin, polyvinylpyrrolidones,
hydroxypropyl celluloses, hydroxypropyl methylcelluloses, pregelatinized starches and
the like; disintegrants such as starches, sodium starch glycolate, pregelatinized starches,
copovidones, croscarmellose sodium, colloidal silicon dioxide and the like; lubricants
such as stearic acid, magnesium stearate, zinc stearate and the like; glidants such as
colloidal silicon dioxide (Syloid, Aerosil, Cab-o-sil etc.) and the like; solubility or
wetting enhancers such as anionic or cationic or neutral surfactants; complex forming
agents such as various grades of cyclodextrins and resins; release rate controlling agents
such as hydroxypropyl celluloses, hydroxymethyl celluloses, hydroxypropyl
methylcelluloses, ethylcelluloses, methylcelluloses, various grades of methyl
methacrylates, waxes and the like. Other pharmaceutically acceptable excipients that are
of use include but are not limited to film formers, plasticizers, colorants, flavoring
agents, sweeteners, viscosity enhancers, preservatives, antioxidants, and the like.
Suitable solvent which can be used for preparing the solid dispersion of
Viloxazine hydrochloride are the same as described in step (a) of third embodiment.
Any undissolved particles in the solution obtained in step (a) may be removed by
suitable method as described herein above or any other technique known in the art.
Step (b) involves isolation of solid dispersion comprising amorphous Viloxazine
hydrochloride and one or more pharmaceutically acceptable carriers.
Isolation of solid dispersion in step (b) may be carried out by removing solvent
from a solution or suspension or mixture obtained in step (a). Suitable techniques which
can be used for the removal of solvent are the same as described in step (b) of third
embodiment or any other technique known in the art.
The solid dispersions of the present invention are prepared using conventional
spray drying techniques, vacuum drying, fluid-bed drying, freeze-drying, rotary
9
evaporation, rotary vacuum paddle dryer, drum drying, or other solvent removal process
known in the art.
Another aspect of the invention involves preparation of solid dispersions of
Viloxazine hydrochloride by melt processing, wherein the compound and a carrier are
heated to a temperature above the melting point of both the carrier and compound, which
results in the formation of a fine colloidal (as opposed to molecular) dispersion of
compound particles, with some solubilization of the compound in the carrier matrix.
Processing of such a molten mixture often includes rapid cooling, which results in the
formation of a congealed mass which must be subsequently milled to produce a powder
which can be filled into capsules or made into tablets.
Recovery of solid dispersion comprising an amorphous form of Viloxazine
hydrochloride and one or more pharmaceutically acceptable polymers or carriers may be
carried out by methods as described in step (b) of third embodiment or any other
technique known in the art.
The resulting solid dispersion comprising an amorphous form of Viloxazine
hydrochloride and one or more pharmaceutically acceptable polymers or carriers may be
optionally further dried. Drying can be carried out by methods as described in step (b) of
third embodiment herein above or any other technique known in the art.
In the fourth embodiment, present application provides a method for preparing a
solid dispersion comprising amorphous Viloxazine hydrochloride and one or more
pharmaceutically acceptable carriers comprising the steps of:
a) physically blending of Viloxazine hydrochloride and one or more
pharmaceutically acceptable carriers; and
b) isolating solid dispersion comprising amorphous Viloxazine hydrochloride
and one or more pharmaceutically acceptable carriers.
Step (a) involves physically blending of Viloxazine hydrochloride and one or
more pharmaceutically acceptable carriers.
Viloxazine hydrochloride substantially in amorphous form may be utilized for
physical blending of Viloxazine hydrochloride in step (a).
10
Suitable pharmaceutically acceptable polymers or carriers that are dispersing
agents which can be used in step (a) are the same as dispersing agents defined in step (a)
of sixth embodiment.
Physical blending as used in step a) involves dry blending in motor pistol, flask
or any other suitable container or any other technique known in the art.
Step (b) involves isolation of solid dispersion comprising amorphous Viloxazine
hydrochloride and one or more pharmaceutically acceptable polymers or carriers which
can be carried out by any technique known in the art.
The amount of Viloxazine hydrochloride in the solid dispersions of the present
invention ranges from about 0.1% to about 90% by weight of the solid dispersion; or
from about 10% to about 70% by weight of the solid dispersion; or from about 20% to
about 60% by weight of the solid dispersion; or from about 20% to about 40% by weight
of the solid dispersion; or about 30% by weight of the solid dispersion. In some aspects,
the weight ratio of Viloxazine hydrochloride to polymer or carrier is about 1:99 to about
99:1. In some aspects, the weight ratio of Viloxazine hydrochloride to polymer or carrier
is about 1:99 to about 75:25 or about 1:99 to about 60: 40. In further aspects, the weight
ratio of Viloxazine hydrochloride to polymer or carrier is about 1:99 to about 15:85;
about 1:99 to about 10:90; or about 1:99 to about 5:95. In further aspects, the weight
ratio of Viloxazine hydrochloride to polymer or carrier is about 25:75 to about 75:25,
about 40:60 to about 60:40 or about 1:1 or about 2:1.
Amorphous form or the solid dispersions of Viloxazine hydrochloride of the
present application can be optionally subjected to a particle size reduction procedures
before or after the completion of drying of the product to produce desired particle sizes
and distributions. Milling or micronization can be performed to achieve the desired
particle sizes or distributions. Equipment that may be used for particle size reduction
include, without limitation thereto, ball mills, roller mills, hammer mills, and jet mills.
In an aspect, the present application provides pharmaceutical formulations
comprising an amorphous form of Viloxazine hydrochloride or solid dispersion
comprising amorphous form of Viloxazine hydrochloride, together with one or more
11
pharmaceutically acceptable carriers. Viloxazine hydrochloride together with one or
more pharmaceutically acceptable carriers of the present application may be formulated
as: solid oral dosage forms such as, but not limited to, powders, granules, pellets, tablets,
and capsules; liquid oral dosage forms such as, but not limited to, syrups, suspensions,
dispersions, and emulsions; and injectable preparations such as, but not limited to,
solutions, dispersions, and freeze dried compositions. Formulations may be in the forms
of immediate release, delayed release, or modified release. Further, immediate release
compositions may be conventional, dispersible, chewable, mouth dissolving, or flash
melt preparations, and modified release compositions that may comprise hydrophilic or
hydrophobic, or combinations of hydrophilic and hydrophobic, release rate controlling
substances to form matrix or reservoir or combination of matrix and reservoir systems.
The compositions may be prepared using any one or more of techniques such as direct
blending, dry granulation, wet granulation, and extrusion and spheronization.
Compositions may be presented as uncoated, film coated, sugar coated, powder coated,
enteric coated, and modified release coated.
Pharmaceutically acceptable excipients that are useful in the present application
include, but are not limited to: diluents such as starches, pregelatinized starches, lactose,
powdered celluloses, microcrystalline celluloses, dicalcium phosphate, tricalcium
phosphate, mannitol, sorbitol, sugar, and the like; binders such as acacia, guar gum,
tragacanth, gelatin, polyvinylpyrrolidones, hydroxypropyl celluloses, hydroxypropyl
methyl celluloses, pregelatinized starches, and the like; disintegrants such as starches,
sodium starch glycolate, pregelatinized starches, copovidones, croscarmellose sodium,
colloidal silicon dioxide, and the like; lubricants such as stearic acid, magnesium
stearate, zinc stearate, and the like; glidants such as colloidal silicon dioxide and the
like; solubility or wetting enhancers such as anionic, cationic, or neutral surfactants;
complex forming agents such as various grades of cyclodextrins and resins; and release
rate controlling agents such as hydroxypropyl celluloses, hydroxymethyl celluloses,
hydroxypropyl methylcelluloses, ethylcelluloses, methylcelluloses, various grades of
methyl methacrylates, waxes, and the like. Other pharmaceutically acceptable
12
excipients that are useful include, but are not limited to, film formers, plasticizers,
colorants, flavoring agents, sweeteners, viscosity enhancers, preservatives, antioxidants,
and the like.
The pharmaceutical dosage form according to the present invention may be
coated with one or more coating materials or uncoated. The coating materials are not
particularly limited and are known to the person skilled in the art.
The pharmaceutical dosage form according to the present invention can further
comprise additional excipients and adjuvants, which are pharmaceutically acceptable
and general coating materials, which are preferably applied as a coating to the
pharmaceutical dosage form of the present invention. Such further excipients and
adjuvants are known to the person skilled in the art.
The pharmaceutical compositions of the present invention are generally
administered orally to patients, which include, but are not limited to, mammals, for
example, humans, in the form of, for example, a hard or soft gelatin capsule, a tablet, a
caplet, pills, granules or a suspension. The pharmaceutical dosage form can be prepared
by methods known in the art, such as direct compression or wet granulation or direct
compression. The compression of the blend to tablet cores can be carried out using a
conventional tableting machine or a rotary compression machine. The tablet cores may
vary in shape and can be, for example, round, oval, oblong, cylindrical or any other
suitable shape. The cores may also vary in size depending on the concentration of the
therapeutic agent.
Viloxazine hydrochloride which may be used as the input in the process for
preparation of the solid states of the present application can be prepared by any process
known in the art.
The solid form of Viloxazine hydrochloride of the present application may be
characterized by means of Powder X-ray Diffraction Pattern (PXRD). Other techniques,
such as solid state NMR, Fourier Transform Infrared (FTIR), differential scanning
calorimetry (DSC) may also be used.
13
The compound of this application is best characterized by the X-ray powder
diffraction pattern determined in accordance with procedures that are known in the art.
PXRD data reported herein was obtained using CuKa radiation, having the wavelength
1.5406 Å and were obtained using Rigaku Desktop X-ray diffractometer, Model:
MiniFlex600. System description: voltage 40 kV, current 15 mA, divergence slit =
1.25°; Sample stage = Reflection. Scan type: Continuous; Detector – Scintillator NaI
(T1); Measurement parameters: Start Position [°2Th.]: 3; End Position [°2Th.]: 40; Step
Size [°2Th.]: 0.02; Scan Speed [°/min]: 1
Certain specific aspects and embodiments of the present application will be
explained in greater detail with reference to the following examples, which are provided
by way of illustration only and should not be construed as limiting the scope of the
application in any manner.
DEFINITIONS
The following definitions are used in connection with the present application
unless the context indicates otherwise. Polymorphs are different solids sharing the same
molecular formula, yet having distinct physical properties when compared to other
polymorphs of the same formula. The abbreviation “MC” mean moisture content.
Moisture content can be conveniently measured, for example, by the Karl Fischer
method.
“Amorphous form” as used herein refers to a solid state wherein the amorphous
content with in the said solid state is at least about 35% or at least about 40% or at least
about 45% or at least about 50% or at least about 55% or at least about 60% or at least
about 65% or at least about 70% or at least about 75% or at least about 80% or at least
about 85% or at least about 90% or at least about 95% or at least about 96% or at least
about 97% or at least about 98% or at least about 99% or about 100%.
All percentages and ratios used herein are by weight of the total composition,
unless the context indicates otherwise. All temperatures are in degrees Celsius unless
specified otherwise and all measurements are made at 25oC and normal pressure unless
14
otherwise designated. The present disclosure can comprise the components discussed in
the present disclosure as well as other ingredients or elements described herein.
As used herein, "comprising" means the elements recited, or their equivalents in
structure or function, plus any other element or elements which are not recited. The
terms "having" and "including" are also to be construed as open ended unless the context
suggests otherwise.
All ranges recited herein include the endpoints, including those that recite a
range "between" two values.
Terms such as "about," "generally," "substantially," or the like are to be
construed as modifying a term or value such that it is not an absolute. Such terms will be
defined by the circumstances and the terms that they modify, as those terms are
understood by those of skill in the art. This includes, at very least, the degree of
expected experimental error, technique error and instrument error for a given technique
used to measure a value.
Where this document refers to a material, such as in this instance, Viloxazine
hydrochloride and its solid state forms thereof by reference to patterns, spectra or other
graphical data, it may do so by qualifying that they are "substantially" shown or as
depicted in a Figure, or by one or more data points. By "substantially" used in such a
context, it will be appreciated that patterns, spectra and other graphical data can be
shifted in their positions, relative intensities and/or values due to a number of factors
known to those of skill in the art.
In addition, where a reference is made to a figure, it is permissible to, and this
document includes and contemplates, the selection of any number of data points
illustrated in the figure which uniquely define that solid state form, within any
associated and recited margin of error, for purposes of identification.
When a molecule or other material is identified herein as "pure", it generally
means, unless specified otherwise, that the material is 99% pure or more, as determined
by methods conventional in art such as high performance liquid chromatography
(HPLC) or optical methods. In general, this refers to purity with regard to unwanted
15
residual solvents, reaction byproducts, impurities, and unreacted starting materials. In
the case of stereoisomers, "pure" also means 99% of one enantiomer or diastereomer, as
appropriate. "Substantially" pure means, the same as "pure except that the lower limit is
about 98% pure or more and likewise, "essentially" pure means the same as "pure"
except that the lower limit is about 95% pure.
As used herein, the term "room temperature" refers to a temperature of from
about 20oC to about 35oC, from about 25oC to about 35oC, from about 25oC to about
30oC, or for example, about 25oC.
As used herein, the term "overnight" refers to a time interval from about 14 hours
to about 24 hours, or about 14 hours to about 20 hours, for example, about 16 hours.
The "polymer" or “carrier” or “excipient” as used herein interchangeably refer to
any substance or mixture of substances which are pharmaceutically acceptable inactive
ingredients.
The term “dispersed” means random distribution of a therapeutically active
substance throughout the carrier.
Certain specific aspects and embodiments of the present application will be
explained in greater detail with reference to the following examples, which are provided
only for purposes of illustration and should not be construed as limiting the scope of the
application in any manner. Reasonable variations of the described procedures are
intended to be within the scope of the present invention. While particular aspects of the
present invention have been illustrated and described, it would be obvious to those
skilled in the art that various other changes and modifications can be made without
departing from the spirit and scope of the invention. It is therefore intended to cover in
the appended claims all such changes and modifications that are within the scope of this
invention.
EXAMPLES
EXAMPLE 1: PREPARATION OF VILOXAZINE HYDROCHLORIDE SOLID
DISPERSION WITH PVP K-30 (1:5 w/w)
,CLAIMS:18
CLAIMS
1. Solid dispersion comprising amorphous form of Viloxazine hydrochloride and
one or more pharmaceutically acceptable carriers.
2. A method for preparing a solid dispersion comprising amorphous Viloxazine
hydrochloride and one or more pharmaceutically acceptable carriers comprising
the steps of:
a) providing a mixture of Viloxazine hydrochloride and one or more
pharmaceutically acceptable carriers in a solvent; and
b) isolating solid dispersion comprising amorphous Viloxazine hydrochloride
and one or more pharmaceutically acceptable carriers.
3. A method for preparing a solid dispersion comprising amorphous Viloxazine
hydrochloride and one or more pharmaceutically acceptable carriers comprising
the steps of:
a) physically blending Viloxazine hydrochloride and one or more
pharmaceutically acceptable carriers; and
b) isolating solid dispersion comprising amorphous Viloxazine hydrochloride
and one or more pharmaceutically acceptable carriers.