Studies on the
development of Orally Disintegrating Tablets of Irbesartan
Kamisetti R Rajeswari, Vinitha
Brungi, S. Bennuru, Sr. Cheeli, RM. Gupta Vankadari
Pulla Reddy Institute of
Pharmacy, Gummadidala, Sangareddy, Dist, Telangana 502313
*Corresponding Author E-mail: drkrajarajeswari@gmail.com
ABSTRACT:
The present work
was aimed to investigate the effects of Β Cyclodextrins and super
disintegrants on the release of the poorly soluble BCS class II drug,
Irbesartan. Orally disintegrating tablets of the drug were prepared with the
inclusion complexes of the drug and various superdisintegrants. A novel
no-calorie sweetening agent was added in the formulation and its effect on the
drug release was also studied. Spectral studies revealed no drug-excipient
compatability exist. Drug inclusion complexes using β cyclodextrins were
prepared by physical mixing, kneading and solvent evaporation methods and characterized.
Complexes of 1:2 ratio were found to have better entrapment efficiency which
was also confirmed by DSC and SEM. Orally disintegrating tablets were prepared
by direct compression methods and evaluated for pre and post compression
parameters. The optimized formulation F2 was found to have a disintegration
time of 5 seconds with a cumulative percentage drug release of 97% in 60
minutes. There was no much difference in the drug release with the addition of
sucralose. A comparative dissolution study of F2 with that of the pure drug,
marketed formulation and formulation without superdisintegrants was performed.
Hence it was concluded that solubility of Irbesartan can be enhanced using
β-cyclodextrins and the orally disintegrating tablets of the drug are suited
for improving onset of action and further bioavailability.
KEYWORDS: Irbesartan,
cyclodextrins, sucralose, direct compression, superdisintegrating agents,
disintegrating time.
INTRODUCTION:
The oral cavity is
a promising route of administration for drugs that are susceptible to hepatic
first-pass metabolism. There are some challenges that complicate the intraoral
administration of drugs[1]. Drug absorption into systemic
circulation through the highly vascularized sublingual and buccal mucosae of the
mouth often achieves a rapid onset of drug action and improved bioavailability
for drugs that are susceptible to a first-pass effect or degradation in the
gastrointestinal tract[2,3].
The concept of Orally disintegrating drug delivery System thus emerged
from the desire to provide patients like pediatric, geriatric, bedridden, or
mentally disabled who face difficulty in swallowing (Dysphagia) conventional
tablets or capsules leading to ineffective therapy when systemic drug
absorption through the oral mucosal membranes is desired, the drug has to
dissolve rapidly in a very small volume of saliva before it is removed from the
site of absorption by swallowing[4]. The taste of the active
drug also needs to be taken into consideration. Since many drugs have a very
bitter or irritating taste, this means that flavours, sweeteners or other
taste-masking approaches usually need to be incorporated into intraorally
dissolving formulations to make them acceptable to the patient[2].
US Food and Drug
Administration Center for Drug Evaluation and Research (CDER) defined Oral
Disintegrating Tablets in the “Orange Book”, as “a solid dosage form containing
medicinal substances, which disintegrates rapidly, usually within a matter of
seconds, when placed upon tongue[3]. The tablets should also possess
adequate mechanical
strength to resist destruction in the course of manufacture and storage.
Recently, the European Pharmacopoeia adopted the term oro dispersible
tablet as a tablet to be placed in the mouth where it disperses rapidly before
swallowing and which disintegrates in less than 3 minutes[2,6].
There was no specification concerning either the hardness or the friability of
this kind of tablets. That is why we find certain Rapidly Disintegrating
Tablets (RDT) in the market that disintegrate in less than 1 minute or maybe 30
seconds, but are brittle and require specified peel able blister packaging and
thus higher costs[3,5]. The tablets should possess palatability with
minimum bitter taste intensity and duration.
The prerequisites for the formulation of or ODT include quick
disintegration and dispersion in the oral cavity without water, optimum drug
entrapment or drug holding capacity, compatibility with taste masking agents
and excipients, and have optimum sensation effect leaving minimum or no residue
after administration These tablets are formulated either by the use of
super or by enhancing pore structure of the tablets by freeze drying and vacuum
drying[4]. Also the ODT
should have optimum capacity to remain intact in formulation processes and
stable at the range of temperature and humidity. ODT combines the
advantages of both liquid and conventional tablet formulations, while also
offering advantages over both traditional dosage forms like enhanced
bioavailability, avoidance of first pass hepatic metabolism and convenience[6,7].
It should be manufactured at low
cost[6-10]. Antihypertensive drugs like Amlodipine besylate
as oral films[11]. ODT of poorly soluble drugs can be
formulated using low viscosity grade HPMC E5LV13, solid dispersion
techniques[12-16]. Fast dissolving tablets of Losartan
potassium, Valsartan and various antiepileptic drugs like
Clonazepam, Pimozide[9] etc have been tried successfully.
The formation of
inclusion complexes with cyclodextrins (CDs) has been demonstrated to increase
the apparent aqueous solubility and dissolution rate of poorly soluble drugs[17-24].
Cyclodextrins and their drug complexes do not easily permeate through biological
membranes and therefore, the complexes need to dissociate in the body before
the active drug can be absorbed.
The main driving
force for the dissociation of inclusion complexes is simple dilution in
biological fluids[25-26].
They are considered
to be virtually nontoxic in peroral administration, and their adverse effects
(i.e. transient diarrhea or soft stools) are similar to those of poorly
digestible carbohydrates[26]. The proposed safe daily intake levels
for natural CDs in peroral administration are 1.9 (α-CD), 0.5 (β-CD),
and 14 (γ-CD)g/kg/day. Taste
masking of the drug is essential as the drug will dissolve close to the taste
buds and interact with the gate-keeper proteins[7]. Thus the ODT
should possess smooth texture and pleasant mouthfeel. Various taste masking
agents like Sucrose, Sacharin, Sorbitol, Aspartame, Xylitol etc have been
tried. It is evident that Cyclodextrins have been successfully used in the
taste masking of bitter drugs. Cyclodextrin inclusion complexes forms complexes
with bitter drugs and the strongly hydrated outer surface of the complex
prevents the binding of the drug to the taste receptors[27].
Sucralose is a
calorie-free artificial sweetener derived from sucrose and 650 times sweeter
than sugar. It is made through a patented, multi-step process that starts with
sugar and selectively replaces three hydrogen-oxygen groups on the sugar
molecule with three chlorine atoms. The result is an exceptionally stable
sweetener that tastes like sugar, but without sugar’s calories. It improves the taste of bitter drugs with
increased efficacy and the convenience of the formulation because of its
positive effects over the glycemic index[28]. It was hence validated
and recommended by the European Food Safety Authority. The accepted daily
intake of sucralose is 15mg/Kg body weight.
Irbesartan
is a BCS Class II angiotensin receptor blocker indicated for the treatment of hypertension. It is a non-peptide compound,
chemically described as a
2-butyl-3-[p-(o-1Htetrazol-5-ylphenyl)benzyl]-1,3-diazaspiro [4.4]
non-1-en-4-one. Irbesartan is a white to off-white crystalline powder with a
molecular weight of 428.5. It is a nonpolar compound with a partition
coefficient (octanol/water) of 10.1 at pH of 7.4. It is slightly soluble in
alcohol and methylene chloride and practically insoluble in water. The oral
absorption of irbesartan is rapid and complete with an average absolute
bioavailability of 60%.
The
drug has been formulated as FDT by solid dispersion technique by spray drying
method using low viscosity grade HPMC E5LV[8]. Cyclodextrins have
been proved as solubility enhancers in various studies. Hence, the objectives
of the present work were focused to investigate the effects of
β-cyclodextrins, Hydroxy propyl β-cyclodextrins, various Super
disintegrants and calorie-free sweetener Sucralose on the solubility,
mechanical strength and release of the drug.
MATERIALS
AND METHODS:
Materials:
Irbesartan
was gifted by Hetero Labs Pvt. Ltd, Hyderabad. β-cyclodextrins,
Sucralose were procured from Essel Fine Chem, Mumbai, Sodium starch Glycholate,
Croscarmellose sodium and Crospovidone were procured from SD Fine Chemicals
Pvt. Ltd. All other chemicals and reagents used were of pharmaceutical grade
and used as received.
Methodology:
Preparation
of drug-cyclodextrin complexes:
The
complexes were prepared according to a previously published procedure[29.30]
using β-cyclodextrins in various ratios like 1:1, 1:2 & 1:3.
Complexes are prepared by physical mixtures, kneading and solvent evaporation
methods.
Physical
Mixture method:
The
required molar (1: 1:2, 1:3) quantities of the drug and cyclodextrins were
weighted accurately and mixed together thoroughly in a mortar, with vigorous
trituration, for about three hours. These mixtures were then passed through
sieve No. 44 and finally stored in airtight containers till further use.
Kneading
Method:
The
required quantities of the drug and the cyclodextrins were weighed accurately
and taken in a mortar to which a mixture of 1:1 ratio of distilled water and
ethanol were added and kneaded continuously for 3 hours to make a paste, dried
in a hot air oven at 45°–50° for 24 hours. The dried complexes were then
powdered and passed through sieve No. 44 and stored in airtight containers till
further use.
Solvent
Evaporation method:
The
required quantities of the drug and the Cyclodextrins were weighed accurately
and dissolved in 10ml of ethanol and continuously stirred by magnetic stirrer
(Remi IB-21886) for about 3 hours until the solvent gets completely evaporated.
The formed solid mass was dried in a vacuum desiccator and the dried solid mass
was pulverized, passed through sieve no. 100 and stored in air tight containers
for further use.
Characterization
of the drug inclusion complexes: Drug content estimation:
The quantities of the drug inclusion complexes equivalent to 75mg of
Irbesartan were dissolved in ethanol. Appropriate dilutions were made and
the drug content of each complex was calculated using UV Spectrophotomter
(Electrolab T60-U) recorded at λmax 270 nm.
IR spectrum analysis:
Infra red (IR) spectra of the drug and inclusion complexes were recorded
using the KBr method using Fourier Transform Infrared Spectrophotometer
(Bruker-Alpha). A baseline correction was made using dried potassium bromide,
and then the spectra of the dried mixtures of drug and inclusion complexes with
potassium bromide were recorded. Structural changes and the
lack of a crystal structure can lead to changes in bonding between functional
groups are detected.
Differential scanning
calorimetric analysis:
This scanning was performed using DSC model (Hitachi 7020).
The samples were placed in a closed platinum crucible and DSC thermograms were
recorded at a heating rate of 10°/minute in the range of 60-260ºC in nitrogen
atmosphere.
Scanning electron
microscopy:
The morphology of the inclusion complexes by physical
mixture, kneading method, and Solvent evaporation was studied using a scanning
electron microscope (Jeol JSM 840). The samples were coated with platinum to
provide a conductive layer for observing images at 15kV accelerating voltage.
Formulation of
Optimized drug- Cyclodextrin complexes as orally disintegrating tablets (ODT):
An amount of the
complex (Irbesartan -CD) equivalent to 15mg of Irbesartan was blended with
directly compressible diluents and superdisintegrants in a plastic bag for 20
minutes. Magnesium stearate, aspartame and talc were passed through a 0.25-mm
sieve, mixed and then blended with the initial mixture in the plastic bag. The
blend was then compressed using a multi-punch tablet press (Rimek Minipress).
The formulations were prepared with a target mass of 150mg (formulations codes
F1–F14). The composition of the formulations is shown in Table I.
Table1:
Formulation of Odt of Irbesartan
|
Formu -lation code |
Drug complex |
SSG |
CP |
CCS |
SUC |
MCC |
MS |
|
F1 |
75 |
5 |
- |
- |
5 |
61 |
4 |
|
F2 |
75 |
10 |
- |
- |
5 |
56 |
4 |
|
F3 |
75 |
15 |
- |
- |
5 |
51 |
4 |
|
F4 |
75 |
- |
- |
5 |
5 |
61 |
4 |
|
F5 |
75 |
- |
- |
10 |
5 |
56 |
4 |
|
F6 |
75 |
- |
- |
15 |
5 |
51 |
4 |
|
F7 |
75 |
- |
5 |
- |
5 |
61 |
4 |
|
F8 |
75 |
- |
10 |
- |
5 |
56 |
4 |
|
F9 |
75 |
- |
15 |
- |
5 |
51 |
4 |
|
F10 |
75 |
10 |
- |
- |
7.5 |
53.5 |
4 |
|
F11 |
75 |
10 |
- |
- |
10 |
51 |
4 |
|
F12 |
75 |
10 |
- |
- |
12.5 |
48.5 |
4 |
|
F13 |
75 |
10 |
- |
- |
15 |
46 |
4 |
|
F14 |
75 |
12.5 |
- |
- |
15 |
43.5 |
4 |
The
quantities of all ingredients are taken in milligrams (mg). Each tablet weighs
150mg.
*MCC:
Micro Crystalline Cellulose; CP: Crospovidone; CCS: Cros Carmellose Sodium;
SSG: Sodium Starch Glycolate; SUC: Sucralose, MS: Magnesium Stearate
Evaluation of Tablets:
All the
formulations were evaluated for pre and post-compression parameters[9]
as described.
RESULTS
AND DISCUSSION:
The drug complexes prepared
were studied for their drug entrapment efficiency and the results were shown in
Table: 2. The drug inclusion complexes of 1:2 ratio prepared by Solvent
evaporation method was found to have an entrapment efficiency of 97% compared
to the other methods.
Table 2: Drug Content Estimation
|
S. No |
Drug inclusion Complex |
Ratio |
% drug content |
|
1 |
Drug: βCD (Physical Mixture) |
01:01 |
45 |
|
2 |
Drug: βCD (Kneading Method) |
60 |
|
|
3 |
Drug: βCD (Solvent Evaporation Method) |
75 |
|
|
4 |
Drug: βCD (Physical Mixture) |
48 |
|
|
5 |
Drug: βCD (Kneading Method) |
01:02 |
65 |
|
6 |
Drug: βCD (Solvent Evaporation Method) |
97 |
|
|
7 |
Drug: βCD (Physical Mixture) |
51 |
|
|
8 |
Drug: βCD (Kneading Method) |
69 |
|
|
9 |
Drug: βCD (Solvent Evaporation Method) |
01:03 |
78 |
The
Drug-Excipient interaction study conducted by Brucker instrument following KBr
pellet method were shown in Fig. 1&2. The nature of the drug has been
confirmed by the absorption bands at their respective wave numbers as shown in
the Table: 3.
It
was observed that there was no much deviation in the existence of absorption
bands between the drug in pure form and drug with excipients. Hence it was
confirmed that there exist no incompatibility between the drug and the
excipients.
Fig.1: FTIR graph of Irbesartan pure drug
Fig.2: FTIR graph of
ODT of Irbesartan
The nature of the drug in pure
form and with the excipients in the form of ODT were studied and compared by
DSC and the results were shown in fig 3&4.
Fig.3: DSC of pure drug
Table3: Ftir Spectral
Data of Drug and Excipients
|
S. No |
Wavenumber formulation (cm-1) |
Characteristic Wavenumber range (cm-1) |
Bond nature and bond attributed |
|
|
Pure drug |
Optimized formulation |
|||
|
1 |
1713.07 |
1715.11 |
1700-1660 |
A strong absorption band due to N-H stretching, C=O stretching deformation. Indicates the presence of Aromatic (Benzene) ring. |
|
2 |
1689.12 |
1679.59 |
1640-1690 |
C=N stretching (Conjugated Cyclic group) |
|
3 |
1415.09 |
1440.94 |
1350-1640 |
N=H bending deformation (amines) and C-H stretching. |
|
4 |
1047.87 |
1024.34 |
1000-1400 |
C-O stretching, strong absorption band |
|
5 |
919.15 |
994.22 |
900-700 |
Mono substituted cycloalkane C-H deformation |
DSC analysis of pure drug and
the formulation showed that the endothermic peak of formulation was observed at
a lower temperature of 174º C compared to that of the drug in pure form which
had a peak at 185º C. This difference can be attributed to the conversion of
crystalline form of the drug to more or less amorphous form which might have an
effect on the enhancement of the solubility of the drug in the formulation.
Fig.4: DSC of ODT of Irbesartan
The
surface morphology and the nature of the drug were studied by Scanning electron
microscopy. The photomicrographs of the drug inclusion complex of Irbesartan
prepared by physical mixing, kneading and solvent evaporation methods were
shown were shown in the fig: 5 a, b, c. It showed that drug has been entrapped
within the hydrophilic carrier β-cyclodextrins represented by the presence
of small rough particles of drug throughout the carrier. The conversion of drug
sample from crystalline to amorphous has been previously revealed by DSC
studies.
All the formulations (F1-F14)
were evaluated for various properties like bulk and tapped densities and flow
properties and the results as shown in the Table: 4 were found to be within the
limits.
The ODT of Irbesartan were evaluated for their post compression
parameters like thickness, hardness, weight variation, friability and
disintegration time. The results were shown in Table: 5.
(a)
(b)
(c)
Fig.5: Drug inclusion complex prepared by
(a)Physical mixing (PM), (b) Kneading method (KM) and (c) Solvent Evaporation
(SE)
In
vitro dissolution studies were performed
for all the tablets (F1-F14). The effect of type and concentration of
superdisintegrants on the drug release (F1-F9) was shown in the Table: 6 and
the drug
release was found to be 97% for F2 compared to all formulations. The better
release might be due to the presence of β-Cyclodextrins which enhanced the
drug solubility and sodium starch glycholate as super disintegrant which had
very less disintegration time of 5 seconds. The effect of Sucralose on the drug
release was shown in Table: 7. Sucralose, a novel no-calorie sweetener was
added as a taste masking agent in the formulation of ODT of Irbesartan. Hence
the effect of sucralose was also studied in various concentrations from F 10 to
F14. But it was observed that there was no much difference in the drug release.
Hence from the above studies it was concluded that F2 was the optimized
formulation.
Table 4:
Precompression Characteristics of The Powder Blend of All Formulations of ODT
Containing Irbesartan-Β-Cyclodextrin Complex (1:2)
|
Formulation |
Angle of repose ( |
Bulk density (gm/cm3) * |
Tapped density (gm/cm3) * |
Hausner’s ratio *
|
Compressibility Index (%) * |
|
F1 |
20.76±0.83 |
0.613±0.007 |
0.682±0.003 |
1.112±0.017 |
10.11±1.414 |
|
F2 |
20.28±0.90 |
0.606±0.005 |
0.661±0.001 |
1.018±0.012 |
8.24±0.947 |
|
F3 |
21.32±0.69 |
0.660±0.010 |
0.750±0.011 |
1.135±0.001 |
11.93±0.084 |
|
F4 |
21.79±0.72 |
0.650±0.002 |
0.738±0.009 |
1.135±0.010 |
11.90±0.813 |
|
F5 |
20.26±1.01 |
0.644±0.006 |
0.732±0.013 |
1.137±0.011 |
12.06±0.841 |
|
F6 |
22.34±0.82 |
0.661±0.008 |
0.746±0.012 |
1.128±0.010 |
11.39±0.782 |
|
F7 |
21.26±0.69 |
0.668±0.010 |
0.758±0.016 |
1.134±0.006 |
11.87±0.816 |
|
F8 |
23.76±0.13 |
0.613±0.007 |
0.682±0.003 |
1.112±0.017 |
10.11±1.414 |
|
F9 |
22.58±0.50 |
0.606±0.005 |
0.661±0.001 |
1.088±0.012 |
8.24±0.947 |
|
F10 |
24.32±0.69 |
0.660±0.010 |
0.750±0.011 |
1.135±0.001 |
11.93±0.084 |
|
F11 |
23.79±0.72 |
0.650±0.002 |
0.738±0.009 |
1.135±0.010 |
11.90±0.813 |
|
F12 |
22.26±1.01 |
0.644±0.006 |
0.732±0.013 |
1.137±0.011 |
12.06±0.841 |
|
F13 |
22.34±0.82 |
0.661±0.008 |
0.746±0.012 |
1.128±0.010 |
11.39±0.782 |
|
F14 |
24.26±0.69 |
0.668±0.010 |
0.758±0.016 |
1.114±0.006 |
11.87±0.816 |
For each value n=3
Table 5: Post Compression Parameters of ODT of Irbesartan
|
Formulation |
Thickness (mm) |
Hardness (Kg/cm2) |
Friability (%) |
Disintegration time (sec) |
|
F1 |
2±0.01 |
2.2±0.03 |
0.25±0.02 |
8.3±0.03 |
|
F2 |
2±0.01 |
2.5±0.05 |
0.28±0.01 |
5.0±0.01 |
|
F3 |
2.2±0.02 |
2.2±0.02 |
0.5±0.05 |
9.4±0.03 |
|
F4 |
2.1±0.05 |
2.2±0.04 |
0.42±0.03 |
12.6±0.02 |
|
F5 |
2.3±0.06 |
2.2±0.06 |
0.35±0.05 |
8.6±0.02 |
|
F6 |
2.1±0.05 |
2.2±0.05 |
0.65±0.03 |
15.3±0.05 |
|
F7 |
2.1±0.03 |
2.2±0.04 |
0.54±0.01 |
13.2±0.06 |
|
F8 |
2.3±0.04 |
2.2±0.01 |
0.32±0.02 |
16.2±0.04 |
|
F9 |
2.2±0.07 |
2.2±0.03 |
0.62±0.03 |
6.3±0.05 |
|
F10 |
2.4±0.06 |
2.2±0.04 |
0.81±0.03 |
17.8±0.03 |
|
F11 |
2.3±0.05 |
2.2±0.05 |
0.42±0.04 |
18.6±0.04 |
|
F12 |
2.2±0.03 |
2.2±0.02 |
0.72±0.05 |
13.4±0.06 |
|
F13 |
2.1±0.03 |
2.2±0.06 |
0.24±0.06 |
12.3±0.04 |
|
F14 |
2.2±0.04 |
2.2±0.02 |
0.35± 0.05 |
13.1± 0.02 |
For each value n=3
Table 6: Dissolution
Profile of ODT of Irbesartan (F1-F9)
The
effect of type and concentration of superdisintegrants on the drug release
|
Time Min |
F1
|
F2 |
F3 |
F4 |
F5 |
F6 |
F7 |
F8 |
F9 |
|
5 |
5.17±0.1 |
6.52±0.1 |
5.52±0.1 |
4.05±0.11 |
4.95±0.09 |
3.71±0.07 |
4.61±0.12 |
4.62±0.07 |
5.51±0.12 |
|
10 |
21.40±0. |
23.21±0. |
18.70±0.1 |
16.45±0.12 |
18.92±0.09 |
49.36±0.14 |
45.29±0.12 |
46.52±0.09 |
18.70±0.09 |
|
15 |
35.78±0.11 |
44.04±0.11 |
36.65±0.10 |
36.22±0.09 |
44.04±0.11 |
47.38±0.12 |
49.23±0.12 |
50.23±0.12 |
39.39±0.10 |
|
20 |
45.55±0.12 |
57.10±0.10 |
40.12±0.12 |
49.36±0.14 |
52.13±0.11 |
44.04±0.11 |
52.13±0.10 |
55.13±0.10 |
54.23±0.11 |
|
25 |
53.45±0.11 |
60.2±0.12 |
56.10±0.12 |
55.05±0.12 |
52.13±0.10 |
56.10±0.12 |
57.10±0.10 |
49.36±0.14 |
58.20±0.11 |
|
30 |
63.25±0.11 |
78.5±0.14 |
62.13±0.09 |
65.14±0.12 |
72.62±0.11 |
85.05±0.011 |
81.14±0.09 |
72.62±0.11 |
81.14±0.09 |
|
45 |
75.36±0.10 |
88.8±0.11 |
78.12±0.12 |
83.02±0.11 |
88.01±0.12 |
85.13±0.12 |
86.54±0.08 |
88.01±0.12 |
86.54±0.08 |
|
60 |
91.13±0.10 |
97±0.013 |
89.95±0.12 |
91.50±0.14 |
93.65±0.11 |
94.23±0.11 |
89.62±0.12 |
94.23±0.09 |
91.51±0.1 |
For each
value n=3
Table 7: Dissolution
Profile of ODT of Irbesartan (F10-F14) Effect of Sucralose on The Drug
Release
|
Time (Min) |
F10 |
F11 |
F12 |
F13 |
F14 |
|
10 |
23.21±0.011 |
17.21±0.08 |
18.7±0.012 |
16.45±0.09 |
18.92±0.012 |
|
15 |
44.04±0.012 |
29.04±0.09 |
36.65±0.02 |
36.22±0.10 |
44.04±0.09 |
|
20 |
57.1±0..09 |
38.05±0.12 |
40.12±0.09 |
49.36±0.09 |
52.13±0.011 |
|
25 |
60.23±0.08 |
46±0..12 |
56.1±0.012 |
55.05±0.12 |
52.13±0.09 |
|
30 |
78.57±0.010 |
65.11±0.09 |
62.13±0.011 |
65.14±0.10 |
72.62±0.010 |
|
45 |
88.81±0.012 |
85.12±0.011 |
78.12±0.012 |
83.02±0.09 |
88.01±0.09 |
|
60 |
96.22±0.010 |
95.89±0.010 |
89.95±0.09 |
91.5±0.10 |
93.65±0.10 |
For each value n=3
Further the dissolution
profiles were studied with optimized formulation F2 and marketed formulation,
pure drug and formulation without super-disintegrant (FF). It showed that at
the end of 60 mins, 97%, 49.04, 76.95 and 39.5% of drug release from F2, FF, Marketed
tablet and pure drug respectively as shown in fig: 6.
Fig.6: Comparitive dissolution
profile.
CONCLUSION:
It can be thus concluded that
solubility of poorly soluble BCS class II drug, Irbesartan can be enhanced by
β-cyclodextrins and the release can be enhanced using superdisintegrants
like sodium starch glycholate and formulated as orally disintegrating
tablets. Considering the benefits of ODT like the drug release in
salivary environment and bypassing hepatic metabolism which might increase the
bioavailability and quick onset of action, ODT are preferred for various drugs.
It was also concluded that sucralose can be added as a safe and recommended
sweetener in the ODT formulations which might further enhance the patients’
compliance.
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Received on 26.11.2019
Modified on 31.12.2019
Accepted on 28.01.2020 ©Asian Pharma Press All
Right
Reserved
Asian J. Pharm. Res. 2020; 10(1):01-07.
DOI: 10.5958/2231-5691.2020.00001.5