Note: Descriptions are shown in the official language in which they were submitted.
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TREATING ALLERGIC AND INFLAMMATORY CONDITIONS
BACKGROUND OF THE INVENTION
This invention relates to the use of desloratadine for the preparation of
a medicament for treating and/or preventing allergic and inflammatory
conditions in a pediatric patient and a pediatric pharmaceutical composition
comprising an amount of desloratadine effective for such treating and/or
preventing.
i_oratadine is disclosed in U.S. Patent No. 4, 282, 233 as a non-
sedating antihistamine useful for treating allergic reactions in animals
including humans. The recommended daily dose of loratadine is 10 mg, once
daily, for adults and children, 12 years of age and older as well as for
children,
ages 6 to 11 ( in the form of the syrup): .
Recent Food and Drug Administration ("FDA") proposed
regulations would require new drugs to include labeling on how such drugs
could be used safely and effectively in pediatric populations. The FDA
Modernization Act further addressed the need for improved information about
the use of medicines in the pediatric population.
There is a need for a safe and clinically effective therapy to treat or
prevent such allergic and inflammatory conditions of the skin and airway
passages in pediatric patients .
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SUMMARY OF THE INVENTION
The present invention provides the use of desloratadine for the
preparation of a medicament for treating and/or preventing an allergic and
inflammatory condition of the skin or airway passages in a pediatric patient
wherein the medicament comprises an effective amount of desloratadine and
a pharmaceutically acceptable carrier.
The present invention also provides a pharmaceutical composition for
treating and/or preventing an allergic and inflammatory condition of the skin
or
airway passages in a pediatric patient which comprises an effective amount of
desloratadine and a pharmaceutically acceptable carrier.
The present invention provides a method of treating and/or preventing
an allergic and inflammatory condition of the skin or airway passages in a
pediatric patient in need of such treating and /or preventing which comprises
administering an amount of desloratadine to the pediatric patient effective
for
such treating and/or preventing.
The present invention also provides a method of treating and/or
preventing seasonal or perennial allergic rhinitis in a pediatric patient
which
comprises administering an amount of desloratadine to the pediatric patient
effective for such treating and/or preventing.
The present invention provides a method of treating and/or preventing
atopic dermatitis or ur'ticaria in a pediatric patient in need of such which
comprises administering an amount of desloratadine to the pediatric patient
effective for such treating and/or preventing.
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Brief Description of the Figures
Figure 1 graphically displays the variation over time (time zero to 96
hrs) of the mean plasma concentrations of desloratadine (ng/mL of plasma)
following (I) a single 5 mL (2.5 mg) dose of desloratadine syrup (0.5 mg/mL)
to pediatric volunteers ages 2-5 years and (ii) a single 10 mL (5.0 mg) dose
of
desloratadine syrup (0.5 mglmL) to healthy adult volunteers ages 18 to 45
years.
Figure 2 graphically displays the variation over time (time zero to 96
hrs) of the mean plasma concentrations of desloratadine (ng/mL of plasma)
following (I) a single 10 mL (5 mg) dose of desloratadine syrup (0.5 mg/mL) to
pediatric volunteers ages 6-11 years and (ii) a single 10 mL (5.0 mg) dose of
desloratadine syrup (0.5 mg/mL) to healthy adult volunteers ages 18 to 45
years.
1 ~ DETAILED DESCRIPTION OF THE INVENTION
The phrase "allergic and inflammatory condition of the skin or airway
passages" as used herein means those allergic and inflammatory conditions
and symptoms found on the skin and in the upper and lower airway passages
?0 from the nose to the lungs. Typical allergic and inflammatory conditions of
the
skin or upper and lower airway passages include seasonal and perennial
allergic rhinitis, non-allergic rhinitis, asthma including allergic and non-
allergic
asthma, sinusitis, colds (in combination with a NSAID, e.g., aspirin.
ibuprofen
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or APAP) and/or a decongestant e.g. pseudoephedrine), dermatitis, especially
allergic and atopic dermatitis, and urticaria and symptomatic dermographism
as well as retinophathy, and small vessel diseases, associated with diabetes
mellitus.
The amount of desloratadine effective for treating or preventing allergic
and inflammatory conditions of the skin or airway passages will vary with the
age, sex, body weight, growth and developmental changes as well as the
severity of the allergic and inflammatory condition of the pediatric patient.
Typically, the amount of desloratadine effective for treating or preventing
such
allergic and inflammatory conditions is in the range of about 2.5 mg/day for
pediatric patients, ages 6 to less than 12 years, about 1.25 mg/day for
pediatric patients, ages 2 to less than 6 years, and about 0.60 to about 0.70
mg/day, preferably about 0.63 mg/day, more preferably about 0.625 mg/day
for pediatric patients, ages 6 months to less than 2 years, in single or
divided
doses, preferably a single daily dose in the form of a syrup.
Desloratadine is a non-sedating long acting histamine antagonist with
potent selective peripheral H1-receptor antagonist activity. Following oral
administration, loratadine is rapidly metabolized to descarboethoxyloratadine
or desloratadine, a pharmacologically active metabolite. In vitro and in vivo
animal pharmacology studies have been conducted to assess various
pharmacodynamic effects of desloratadine and loratadine. In assessing
antihistamine activity in mice (comparison of ED5o value), desloratadine was
relatively free of producing alterations in behavior alterations in behavior,
neurologic or autonomic function. The potential for desloratadine or
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loratadine to occupy brain H1-receptors was assessed in guinea pigs
following i.p. administration and results suggest poor access to central
histamine receptors for desloratadine or loratadine.
In vivo studies also suggest that an inhibitory effect of desloratadine on
allergic bronchospasm and cough can also be expected.
The clinical efficacy and safety of desloratadine has been documented
in over 3,200 seasonal allergic rhinitis patients in 4 double-blinded,
randomized clinical trials. The results of these clinical studies demonstrated
the efficacy of desloratadine in the treatment of adult and adolescent
patients
with seasonal rhinitis.
Efficacy endpoints in all the studies were Total Symptom Score, Total
Nasal Symptom Score, Total Non-nasal Symptom Score, and Health Quality
of Life (HQOL) analysis in efficacy trials. Desloratadine (5 mg once daily)
significantly reduced the total symptom scores (the sum of individual scores
for rhinorrhea, sneezing, congestion/stuffiness, nasal itching, itchy/burning
eyes. tearing, ocular redness, and itchy ears/palate). Desloratadine (5 mg)
was significantly (p<0.01 ) more effective than placebo in reducing nasal
symptoms. An important efficacy endpoint analyzed in the desloratadine
studies is the AM NOW total symptom score. This parameter measures the
total symptom relief by the patient after 24 hours before taking the next day
dose. Statistically significant (p<0.05) reductions were maintained for the
full
24 hour dosing interval over the entire dosage range
There were no significant differences in the effectiveness of
desloratadine (over the entire dosage range) across subgroups of patients
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defined by gender, age, or race. Desloratadine is particularly useful for the
treatment and prevention of the nasal (stuffiness/congestion, rhinorrhea,
nasal
itching, sneezing) and non-nasal (itchy/burning eyes, tearing/watery eyes,
redness of the eyes, itching of the ears/palate) symptoms of seasonal allergic
rhinitis, including nasal congestion, in patients in need of such treating
and/ or
preventing.
CLINICAL STUDY DESIGNS
Study Treatments
Subjects were confined to the study site at least 12 hours prior to each
treatment administration. In the morning of Day 1 following a 10 hour
overnight fast, each subject received one of the following treatments based on
his/her subject number and the study period: fasting (Treatment A) or did not
eat again (Treatment B) until the 4-hour study procedures were completed, at
which time lunch was served. Water was permitted throughout the fasting
period except for 2 hours following treatment administration. The subjects
remained awake and seated upright/ambulatory for 4 hours post-dose. A
physician was present at the time of dosing and remained on site until at
least
4 hours post-dose. Subjects were under medical supervision throughout their
confinement at the study site. Each treatment administration was separated
by at least a 7 day washout period.
Pharmacokinetics
Biood samples were collected for determination of the plasma
pharmacokinetic profile of desloratadine. Fifteen milliliters (15mL) of blood
were collected just prior to drug administration (0 hour) and at pre-specified
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times after dosing in both periods. All blood samples were collected into
heparin-containing tubes at the specified times. The blood samples were
centrifuged within 30 minutes after collection for 20 minutes at approximately
4°C and at approximately 3000 rpm. The plasma was separated and
transferred into two separate appropriately labeled tubes, frozen to at least -
20°C and maintained in the frozen state until assayed for desloratadine
content.
The plasma concentration data for desloratadine were used to estimate
the following pharmacokinetic parameters using standard methodologies well
known to those skilled in the art.
The major pharmacokinetic variables of interest were the plasma AUC
and Cmax. All plasma samples were assayed for desloratadine
concentrations using a validated method such as gas/liquid chromatography
with a NP detector(GLC/NPD). The validation of the assay methods included
1~ documentation of its selectivity, limit of quantitation, linearity,
precision and
accuracy. The lower limit of quantitation (LOQ) of the assay was established
at 0.1 ng/mL for desloratadine.
Safety Measurements Assessed
For safety evaluation, physical examinations, vital signs,
electrocardiograms and clinical laboratory tests were conducted at screening
and at the conclusion of the study. In addition, vital signs were monitored
prior to treatment administration and daily during both treatment periods.
Additional clinical laboratory tests and ECGs were obtained prior to dosing in
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each treatment period. The assessment, severity and relationship to
treatment of adverse events were evaluated .
Study No. 1
The objective of this study was to evaluate the effect of food on the
bioavailability of desloratadine. These adult studies were designed to define
the
bioavailability/bioequivalence (BRIBE) relative to the tablet formulation, the
effect of food on the pharmacokinetics following administration of the syrup
formulation and the pharmacokinetic profile of desloratadine after single dose
administration of the syrup to healthy male and female adult subject
Single-Dose BRIBE Study
This was a Phase I, randomized, open-label, three-way crossover
study in 30 healthy adult subjects (ages 18 to 45) who received a 5mg
desloratadine tablet and 10 mL of desloratadine syrup (0.5 mg/mL) under
fasted conditions as well as following a high-fat, high-calorie breakfast on
three separate occasions.
Subjects were confined at the study site at least 12 hours prior to each
treatment (Day -1 ). In the morning of Day 1 following a 10 hour overnight
fast,
each subject received one of the following treatments based on his/her
subject number and the study period:
Treatment A: One desloratadine (DL) 5 mg tablet
administered after a 10 hour fast.
Treatment B: Ten (10) mL of DL syrup (0.5 mg/mL)
following a 10 hour fast
Treatment C: Ten (10) mL DL syrup (0.5 mg/mL)
administered immediately following a
standardized high-fat, high caloric
brew kfast.
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Subjects randomized to receive the standardized high-fat, high caloric
breakfast (Treatment C) consumed the prescribed meal in a 20-minute period
prior to drug administration and received the appropriate dose of
desloratadine within 5 minutes after completing the breakfast.
Study Population) Inclusion Criteria/ Exclusion Criteria
Inclusion Criteria:
~ Subjects were males or females between the ages of 18 and 45
years inclusive, and had a Body Mass Index (BM/) between 19-27.
~ Clinical laboratory tests (CBC, blood chemistries, urinalysis) were
within normal limits or clinically acceptable to the
Investigator/Sponsor .
~ Drug screen for drugs with a high potential for abuse were negative
at screening and on admission to the study site.
~ Subjects were free of any clinically significant disease that required
a physician's care and/or may have interfered with study
evaluations, procedures or participation.
~ Subject gave written informed consent (prior to any study-related
procedures being performed) and were willing to adhere to
restrictions and examination schedules.
~ Subjects had a normal or clinically acceptable physical examination
and ECG .
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Exclusion Criteria:
~ Subjects who had a history of any clinically significant local or
systemic infectious disease within four weeks prior to initial
treatment administration.
~ Subjects who did not comply with the requirement that he or she
should not have used any drugs (except acetaminophen) within 14
days prior to the study nor alcohol or xanthine-containing
substances with 72 hours prior to study drug administration.
10 ~ Subjects who had participated in a clinical trial of any investigational
drug within 30 days prior to the start of the study.
Subjects who were, or were known to be former, narcotic addicts or
alcoholics.
~ Subjects who were positive for hepatitis B surface antigen or
hepatitis C antibody.
~ Subjects who were positive for HIV antibodies.
~ Subjects who had a clinically significant history of food or drug
allergy.
~ Subjects who had a known allergy or intolerance to loratadine.
~ Subjects who smoked, used tobacco products or used an adjunct to
smoking cessation within the past 6 months (positive urine test).
~ Females who were not surgically sterilized or were considering
reversal of their surgical sterilization or were not at least 1 year
post-menopausal.
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~ Females who had a positive urine pregnancy test at screening or on
admission to the study site.
~ Females who were lactating.
Study Treatments
Subjects were confined to the study site at least 12 hours prior to each
treatment administration. In the morning of Day 1 following a 10-hour
overnight fast, each subject received one of the following doses.
Each dose was administered with 180 mL (6 fl oz) of non-carbonated
room temperature water. The tablet was swallowed whole, not chewed or
crushed. After dosing, the oral cavity will be inspected to assure that the
subject had swallowed the tablet/syrup. For subjects randomized to
Treatment B or Treatment C the study medication was administered by having
the volunteer drink the entire 10 mL of desloratadine syrup, followed by two
10 mL tap water rinses of the dose container (i.e., oral syringe, etc.) to
ensure
complete dose intake. Subjects continued fasting (Treatment A and B) or did
not eat again (Treatment C) until the 4-hour study procedures were
completed, at which time lunch was served. Water was permitted throughout
the fasting period except for 2 hours following treatment. The subjects
remained awake and seated upright/ambulatory for 4 hours post-dose.
All subjects were confined to the study site until the 120-hour blood
samples, vital signs and laboratory tests were obtained. No strenuous
physical activity was permitted, and the subjects were not allowed visitors
while they were confined to the study site. A washout period of at least 14
days separated each period of the study.
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The mean pharmacokinetic profiles of desloratadine following single
dose administration of the syrup formulation under fasted conditions are
illustrated in Figure 1.
Study No.2
Single-Dose PHARMACOKINETICS in Pediatric Subjects !,>_2 to <6
Years Old)
The objective of this open label study was to characterize the
pharmacokinetic profile of desloratadine and 3-OH desloratadine following a
single dose of 5 mL (2.5 mg) desloratadine syrup (0.5 mg/mL) administered
orally to healthy pediatric subjects ranging in age from >_2 to <6 years.
These
pediatric subjects were found to have normal or clinically acceptable
laboratory tests be free of any clinically significant disease and to have
normal
or clinically acceptable ECGs
A total of 18 healthy pediatric subjects (12 males and 6 females) with at
least 4 subjects in the following age groups: >_2 but <3, >_3 but <4, >_4 but
<5,
>_5 but <6 were enrolled and successfully completed this open-label, single-
center study. In this study, each subject received a single 5 mL (2.5 mg) dose
of desloratadine syrup (0.5 mglmL) administered orally.
Subjects were screened within 3 weeks of dosing, and those who met
the entry criteria were confined to the study center within 24 hours prior to
dosing. Upon confinement, the clinical laboratory safety tests performed at
Screening were repeated for each subject. The next morning all subjects
received the study medication. Vital signs were obtained daily. Blood
samples were collected at pre-specified times before and after dosing for
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safety and pharmacokinetic evaluations. Subjects were continually observed
and questioned throughout the study for the possible occurrence of adverse
events. Subjects were also instructed to report any unusual experiences or
discomfort. No strenuous physical activity was permitted, and the subjects
were not allowed visitors (besides the parents or legal guardians) while they
were confined to the study site. Following the 24-hour study-related
procedures for safety and pharmacokinetic evaluations, subjects were
dismissed from the study site. They returned to the study site on Days 3, 4
and 5 for the 48-hour, 72-hour and 96-hour study-related procedures.
Following completion of all study-related procedures on Day 5, subjects were
discharged from the study.
The mean plasma concentration-time (0-96 hrs) profiles of
desloratadine following administration of desloratadine to pediatric subjects
>_2 to <6 years old and adults 18 to 45 years old are illustrated in Figure 1.
The derived pharmacokinetic parameters are provided in Table 1.
Table 1. Mean Pharmacokinetic Parameters
The Mean (%CV)
Pharmacokinetic
Parameters of
Desloratadine
Following OraI,Single-Dose
Administration
of 5.0 & 2.5 mg
of
Desloratadine under
Fasted Conditions:
Mean %CV '
Syrup N Cmax(nglmL) AUC(96)(ng.hrlmL)
Data
Adults(5mg) 30 2.19 45.2
Pediatrics(>_2 18 5.36 98.6
to
<6yr,
2.5mg)
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1. %CV is percent coefficient of variation, which is a relative measure of
variability. See Steele and Torrie, "Principles and Procedures of Statistics",
(1980) 2"d Edition, McGraw-Hill, NY, at page 27.
Single oral doses of 5 mL ( 2.5 mg) of desloratadine syrup
administered to healthy pediatric volunteers >_2 to <6 years of age was safe
and well tolerated. To obtain similar systemic exposure in pediatric subjects
(>_2 to <6 years of age) as found in adults administered a 5 mg dose, the 2.5
mg dose should be reduced by 50% to 1.5 mg (See Study No.4).
Study No. 3
SincLe-Dose PHARMACOKINETICS in Pediatric Subjects
(>_6 to <12 Years Oldl
This open-label study in 18 healthly pediatric subjects was designed to
characterize the pharmacokinetic profile of desloratadine and 3-OH
desloratadine following a single 2.5 mg (5mL) dose of desloratadine syrup
administered orally to healthy pediatric volunteers ranging in age from >_6 to
<12 years. These pediatric patients were found to have normal or clinically
acceptable laboratory tests be free of any clinically significant disease and
to
have normal or clinically acceptable ECGs
The objective of this study was to characterize the pharmacokinetic
profile of desloratadine following a single dose of 10 mL (5 mg) desloratadine
syrup (0.5 mg/mL) administered orally to healthy pediatric subjects ranging in
age from >_6 to <12 years.
A total of 18 healthy pediatric subjects (9 males and 9 females) with at
least 3 subjects in the following age groups: >_6 but <7, >_7 but <8, >_8 but
<9,
>_9 but <10, >_10 but <11, and >_11 but <12 were enrolled and successfully
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completed this open-label, single-center study. In this study, each subject
received a single 10 mL (5 mg) dose of desloratadine syrup (0.5 mg/mL)
administered orally.
Subjects were screened within 3 weeks of dosing, and those who met
the entry criteria were confined to the study center within 24 hours prior to
dosing. Upon confinement, the clinical laboratory safety tests performed at
Screening were repeated for each subject. The next morning all subjects
received the study medication. Vital signs were obtained daily. Blood
samples were collected at pre-specified times before and after dosing for
10 safety and pharmacokinetic evaluations. Subjects were continually observed
and questioned throughout the study for the possible occurrence of adverse
events. Subjects were also instructed to report any unusual experiences or
discomfort. No strenuous physical activity was permitted, and the subjects
were not allowed visitors (besides the parents or legal guardians) while they
15 were confined to the study site. Following the 24-hour study-related
procedures for safety and pharmacokinetic evaluations, subjects were
dismissed from the study site. They returned to the study site on Days 3, 4
and 5 for the 48-hour, 72-hour and 96-hour study-related procedures.
Following completion of all study-related procedures on Day 5, subjects were
discharged from the study.
The mean plasma concentrations of desloratadine following
administration of (i) a single 5mL (2.5mg) dose of desloratadine syrup
(0.5mg/mL) to pediatric subjects (ages >_6 to <12) and (ii) a single 10mL
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(S.Omg) dose of desloratadine syrup (0.5mg/mL) to adult subjects (ages 18 to
45).
J
The derived pharmacokinetic parameters are provided in Table 2
Table 2 Mean Pharmacokinetic Parameters
The Mean (%CV)
Pharmacokinetic
Parameters of
Desloratadine
Following Oral,
Single-Dose Administration
of 5.0 mg of
Desloratadine under
Fasted Conditions:
Mean (%CV) '
Syrup N Cmax(nglmL) AUC(96)(ng.hrlmL)
Data
Adults(5mg) 30 2.19 45.2
Pediatrics(>_6 18 5.3 101
to
<12yr,
5.Omg)
1. %CV is percent coefficient of variation, which is a relative measure of
variability. See Steele and Torrie, "Principles and Procedures of Statistics",
(1980) 2"d Edition, McGraw-Hill, NY, at page 27.
Single oral doses of desloratadine syrup administered to healthy
pediatric subjects >_6 to <12 years of age was safe and well tolerated. To
obtain similar systemic exposure in pediatric subjects (>_6 to <12 years of
age)
as in adults administered 5 mg, the dose should be reduced by 50% to 2.5mg
(See Study No.5).
Based on the findings of the studies pharmacokinetic studies will be
repeated in pediatric subjects between the ages of >_2 to < 6 years and >_6 to
<
12 years.
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Study No.4
SINGLE DOSE PHARMACOKINETICS OF DESLORATADINE SYRUP IN
HEALTHY PEDIATRIC VOLUNTEERS 2-5 YEARS OF AGE
Study Objective:
The objective of this open label study will be to characterize the
pharmacokinetic profile of desloratadine following a single dose of 2.5 mL
(1.25 mg) desloratadine syrup (0.5 mg/mL) administered orally to healthy
pediatric subjects ranging in age from >_2 to <6 years. These pediatric
subjects
selected for inclusion into this open label study should have normal or
clinically acceptable laboratory tests, be free of any clinically significant
disease and have normal or clinically acceptable ECGs
Study Design:
A total of eighteen (18) healthy male or female pediatric volunteers
with at least three subjects at each age stratification-will receive a single
dose
of 2.5 mL (1.25mg) of desloratadine syrup (0.5 mg/mL) administered orally.
The protocol of Study No. 2 will be followed
Study Endpoints:
The following pharmacokinetic parameters will be obtained from the
resulting desloratadine concentration-time profiles:
~ Area under the concentration-time curve (AUC o_f, AUC o_c)
~ Peak concentration (CmaX)
~ Time to peak concentration (T~,ax)
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Study No. 5
SINGLE DOSE PHARMACOKINETICS OF DESLORATADINE SYRUP IN
HEALTHY PEDIATRIC VOLUNTEERS >_6 to <12 YEARS OF AGE
Study Objective: The objective of this open label study will be to
characterize the pharmacokinetic profile of desloratadine and 3-OH
desloratadine following a single dose of 5.0 mL (2.5 mg) desloratadine syrup
(0.5 mg/mL) administered orally to healthy pediatric subjects ranging in age
from >_6 to <12 years. These pediatric patients selected for inclusion into
this
open label study should have normal or clinically acceptable laboratory tests,
be free of any clinically significant disease and have normal or clinically
acceptable ECGs
Study Design:
A total of eighteen (18) healthy male or female pediatric volunteers
ages from >_6 to <12 years -with at least three subjects at each age
stratification will receive a single dose of 5 mL (2.5 mg) desloratadine syrup
(0.5 mg/mL) administered orally. The protocol of Study No. 3 will be followed
Study Endpoints:
The following pharmacokinetic parameters will be obtained from the
resulting desloratadine concentration-time profiles:
~ Area under the concentration-time curve (AUC o_x, AUC o-t)
~ Peak concentration (Cr"ax)
~ Time to peak concentration (Tmax)
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U.S.Patent No. 4,659,716 discloses methods of making desloratadine,
pharmaceutical compositions containing it and methods of using
desloratadine and pharmaceutical compositions containing it to treat allergic
reaction in mammals.
U.S.Patent No. 5,595,997 discloses pharmaceutical compositions
containing desloratadine and methods of using desloratadine for treating and
preventing various disease states, e.g., allergic rhinitis.
Desloratadine is available from Schering Corporation, Kenilworth, N.J.
The desloratadine syrup (0.5mg/ml) is disclosed in International Patent
Application PCT/US99/10469 having an international application date of
27/05/99
The pharmaceutical compositions of desloratadine can be adapted for
any mode of administration e.g., for oral, parenteral, e.g., subcutaneous
('SC"), intramuscular ("IM"), and intraperitoneal ("IP"), topical or vaginal
l~ administration or by inhalation (orally or intranasally). Preferably
desloratadine
is administered orally.
Such pharmaceutical compositions may be formulated by combining
desloratadine or an equivalent amount of a pharmaceutically acceptable salt
thereof with a suitable, inert, pharmaceutically acceptable carrier or diluent
that may be either solid or liquid. Desloratadine may be converted into the
pharmaceutically acceptable acid addition salts by admixing it with an
equivalent amount of a pharmaceutically acceptable acid. Typically suitable
pharmaceutically aceptable acids include the mineral acids, e.g., HN03,
H2S04, H3P04 , HCI, HBr, organic acids, including, but not limited to, acetic,
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trifluoroacetic, propionic, lactic, malefic, succinic, tartaric, glucuronic
and citric
acids as well as alkyl or arylsulfonic acids, such as p-toluenesulfonic acid,
2-
naphthalenesulfonic acid, or methanesulfonic acid. The preferred
pharmaceutically acceptable salts are trifluoroacetate, tosylate, mesylate,
and
chloride. Desloratadine is more stable as the free base than as an acid
addition salt and the use of the desloratadine free base in pharmaceutical
compositions of the present invention is more preferred.
Solid form preparations include powders, tablets, dispersible granules,
capsules, cachets and suppositories. The powders and tablets may be
10 comprised of from about 5 to about 95 percent active ingredient. Suitable
solid carriers are known in the art, e.g. magnesium carbonate, magnesium
stearate, talc, sugar or lactose. Tablets, powders, cachets and capsules can
be used as solid dosage forms suitable for oral administration. Examples of
pharmaceutically acceptable carriers and methods of manufacture for various
15 compositions may be found in A. Gennaro (ed.), Remington's Pharmaceutical
Sciences, 18th Edition, (1990), Mack Publishing Co., Easton, Pennsylvania.
Liquid form preparations include solutions, suspensions and emulsions.
As an example may be mentioned water or water-propylene glycol solutions
for parenteral injection. Solid form preparations may be converted into liquid
20 preparations shortly before use for either oral or administration.
Parenteral
forms to be injected intravenously, intramuscularly or subcutaneously are
usually in the form of sterile solutions and may contain tonicity agents
(salts or
glucose), and buffers. Opacifiers may be included in oral solutions,
SUBSTITUTE SHE':T tRUE_E 25)
CA 02393837 2002-06-06
WO 01/45688 PCT/IJS00/34418
21
suspensions and emulsions. Liquid form preparations may also include
solutions for intranasal administration.
Aerosol preparations suitable for inhalation may include solutions and
solids in powder form, which may be in combination with a pharmaceutically
acceptable carrier, such as an inert compressed gas, e.g., nitrogen.
Also included are solid form preparations which are intended to be
converted, shortly before use, to liquid form preparations for either oral or
parenteral administration. Such liquid forms include solutions, syrups
suspensions and emulsions.
Preferably, the pharmaceutical preparation is in a unit dosage form. In
such form, the preparation is subdivided into suitably sized unit doses
containing appropriate quantities of the active component, e.g., an effective
amount to achieve the desired purpose.
SUBSTITUTE SHEET (RULE 26)
