solid state characterization and in vitro dissolution
TRANSCRIPT
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SOLID STATE CHARACTERIZATION AND IN VITRO DISSOLUTION
ENHANCEMENT OF IRBESARTAN BY SOLID DISPERSION
ADSORBATE TECHNIQUE
Dipak R. Yadav* and Dr. S. K. Shah1
*Saraswati Institute of Pharmaceutical Sciences, Dhanap, Gandhinagr-382355, Gujarat.
1Department of Pharmaceutics, Principal, Saraswati Institute of Pharmaceutical Sciences,
Dhanap, Gandhinagr-382355, Gujarat.
ABSTRACT
Various processes were used for the solubility enhancement of
Irbesartan, solid dispersion adsorbate technique is one of them. The
improvement in solubility and in-vitro drug release were observed. The
in-vitro drug release of solid dispersion adsorbate of PEG 4000 and
Poloxamer 188 prepared by fusion method was significantly improved
the dissolution compared to solid dispersion of PVP K-30 and pure
drug. The in-vitro release studies showed 90% of drug release in 30
minutes. Solid-state characterization based on FT-IR spectroscopy,
DSC and in vitro dissolution study was carried out to investigate the
mechanisms of carrier dissolution enhancement. Enhanced Solubility
and dissolution rate of Irbesartan show dissolution rate limited absorption and the onset of
action is beneficial to treat hypertensive patients. Overall, the formulations FENPEG (1:3)
and FENPOL (1:3) which showed better in-vitro dissolution profile, lower MDT and f2
values. Tablets of FENPEG (1:3) prepared and compared with pure drug tablets and marketed
formulation. Tablets of FENPEG (1:3) gives highest drug release 99% in 60 min. additionally
the prepared tablets checked for stability study and found stable after 1 month. Hence, based
on above results it concluded that the FENPEG (1:3) was optimized formulation.
KEYWORDS: Solid Dispersion, Adsorbate, Irbesartan.
INTRODUCTION[1,4]
Solid Dispersion Adsorbates were ready like that of Solid Dispersion, however solely
WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
SJIF Impact Factor 7.421
Volume 7, Issue 5, 1137-1155 Research Article ISSN 2278 – 4357
Article Received on
04 March 2018,
Revised on 24 March 2018,
Accepted on 14 April 2018
DOI: 10.20959/wjpps20185-11538
*Corresponding Author
Dipak R. Yadav
Saraswati Institute of
Pharmaceutical Sciences,
Dhanap, Gandhinagr-
382355, Gujarat.
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distinction was Neusilin US2 (selected adsorbent) was more once the preparation of
homogeneous suspension as that in Solid Dispersion formulation. The co-melt of carrier and
also the drug was adsorbable singly on to the surface of Neusilin US2 to arrange free flowing
granules of solid dispersion adsorbates. Dissolution rates for Solid Dispersion Adsorbates
were bigger than Solid Dispersion. the improved dissolution rates of Solid Dispersion
Adsorbates is also because of several factors like diminished particle size of drug, specific
style of drug in these Solid Dispersion Adsorbates, additionally to the rise in drug wettability
and preventing of drug aggregation by every compound.
Neusilin ® was employed in this investigation as associate degree adsorbent. It exhibits high
specific space, enlarged surface sorption, porosity, anti-caking and flow enhancing properties.
The H bonding potential of silanol within the native surroundings on oxide surfaces is well
documented. Within the gift investigation, a mixture of solid dispersion and soften sorption
technology was used to arrange Solid Dispersion Adsorbate. The solid dispersions adsorbates
were characterised by fourier remodel infrared spectroscopic analysis (FTIR), differential
scanning measure (DSC) and diffraction study (XRD). The Solid Dispersion Adsorbate could
be a promising and a unique approach for the dissolution enhancement and will be used for
the event of appropriate solid dose kind for commercialisation.
The aim of present study is to prepare solid dispersion adsorbate of Irbesartan by solid
dispersion adsorbate technique. Preparation, Evaluation and optimization of Solid dispersion
adsorbate tablets to achieve more than 80% drug release after 30 min in drug release study.
MATERIALS AND METHODS
Instruments and Apparatus
Digital weighing balance (Reptech weighing balance Ltd, Ahmadabad), Tablet punching
machine (Hardik Engineering work, Ahmadabad), Hardness tester (Monsanto Hardness
tester, Ahmadabad), Disintegrator apparatus (Electrolab Ltd, Mumbai) Dissolution apparatus
(Electrolab Ltd, Mumbai), Friabilator apparatus (Electrolab Ltd, Mumbai), Bulk density
apparatus (Electrolab Ltd, Mumbai.)UV spectrophotometer (Shimadzu 1601, Kroyoto,
Japan.), FTIR (FTIR 8400S, Shimadzu, Kroyoto, Japan.)
DSC(DSC TA-60WS, Kroyoto, Japan.)
Ingredients and Excipients
Irbesartan (Torrent Pharmaceutical LTD), Neusilin US2 (Gangwal Chemicals, Mumbai,
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India), PVP K-30 (ACS chemicals, Ahmedabad), Poloxamer 188 (ACS chemicals,
Ahmedabad), PEG 4000, (ACS chemicals, Ahmedabad) Talc, Lactose, Magnisum stearate
(ACS chemicals, Ahmedabad).
Pre-Formulation Study[5,8]
Characterization of Drug (Irbesartan)
Organoleptic Characteristics
Colour of Drug was characterized and recorded using descriptive terminology.
Flow Properties
1) Bulk density and tapped density
An accurately weighed quantity of the blend (W), was carefully poured into the graduated
cylinder and the volume (Vo) was measured. Then the graduated cylinder with lid, set into the
density determination apparatus (Tapped Density Apparatus) the density apparatus was set for
100 taps and after that the volume (Vf) was measured which was tapped volume. The bulk
density and tapped density were calculated by using the following formulas.
Bulk density = W/ V0 Tapped density = W/ Vf
2) Compressibility index (CI) / Carr’s index
It was obtained from bulk and tapped densities. It was calculated by using the following
formula.
% Carr’s index = (T.D. - B.D. ÷ T.D.) × 100
3) Hausner’s ratio
Hausner’s ratio is a number that is correlated to the flow ability of a powder. It is measured
by ratio of tapped density to bulk density.
Hausner’s ratio = (Tapped density ÷ Bulk Density)
4) Angle of repose
Angle of repose of powder was determined by the funnel method. Accurately weight powder
blend were taken in the funnel. Height of the funnel was adjusted in such a way the tip of the
funnel just touched the apex of the powder blend. Powder blend was allowed to flow through
the funnel freely on to the surface. Diameter of the powder cone was measured and angle of
repose was calculated using the following equation.
Tan θ= h/r
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Identification of drug by FTIR[9]
The Fourier transform infrared spectrum of moisture free powdered sample of Drug was
recorded on IR spectrophotometer. The range of spectra was found to be 600 to 4000cm-1
The
characteristics peaks of different functional group were compared with reported standard
peak.
DSC Study of Irbesartan[9]
Differential Scanning Calorimeter allows the fast evaluation of possible incompatibilities,
because it shows changes in the appearance, shift of melting endotherms and isotherms’,
and/or variations in the corresponding enthalpies of reaction. The DSC thermograms of pure
drug recorded.
Calibration Curve[10,14]
Preparation of standard calibration curve of Irbesartan.
Principle: The Irbesartan exhibits peak absorbance at 250 nm in Water and Methanol in ratio
of (9:1).
Instrument used: Shimadzu, UV Spectrophotometer, Japan.
Procedure
Preparation of standard solution: 10 mg of Irbesartan was accurately weighed in to 100 ml
volumetric flask and dissolved in small quantity of water: methanol (90:10).
Preparation of working standard solutions: From standard solution of 100 ml, aliquots of
1ml, 2ml, 3ml, 4ml and 5ml were pipetted into 10ml volumetric flasks. The volume was
made up distilled water get the final concentration of 10μg/ml, 20 μg/ml, 30μg/ml,
40μg/ml and 50μg/ml respectively. The absorbance of each concentration was measured
at 250 nm. The Beer’s range is 10-50μg/ml.
Phase Solubility
Phase-solubility studies were performed by the method of Higuchi and Connors. IRB, in
constant amounts (5 mg) that exceeded its solubility, was transferred to screw capped vials
containing 20 ml of aqueous solution of PVP K-30, Poloxamer 188 and PEG 4000 at various
molar concentration. The contents were stirred on rotary shaker (Remi, India) for 72 hrs. At
370C ± 0.1°C and 300 rpm. The time duration was fixed based on pilot experiment and found
to be sufficient to achieve equilibrium of mixture. After reaching equilibrium, samples were
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filtered through a 0.22 μm membrane filter, suitably diluted and analyzed
spectrophotometrically for drug content at 230 nm. Solubility studies were performed in
triplicate. The solubility of Irbesartan in pure water is 0.0084 mg/ml.
Solid Dispersion of Irbesartan
As we know that Irbesartan belongs from BCS class II which have low solubility. So first of
all we are going to enhance solubility of Irbesartan.
A) Physical mixture
Physical mixture (PM) of PVP K-30, PEG 4000 and Poloxamer 188 with Irbesartan was
prepared by geometric mixing of Irbesartan respectively without applying pressure. The
required quantities of Irbesartan with PVP K-30, PEG 4000 and Poloxamer 188 respectively
were taken in a glass mortar and mixed for 15 minutes. Each carrier was taken in drug: carrier
ratio of 1:1, 1:2 and 1:3.
Drug polymer ratio for solid dispersion
Formulation Code Drug : Carrier ratio Carrier
PMPVP(1:1) 1:1 PVP K 30
PMPVP(1:2) 1:2 PVP K 30
PMPVP(1:3) 1:3 PVP K 30
Formulation Code Drug : Carrier ratio Carrier
PMPEG(1:1) 1:1 PEG 4000
PMPEG(1:2) 1:2 PEG 4000
PMPEG(1:3) 1:3 PEG 4000
Formulation Code Drug : Carrier ratio Carrier
PMPOL(1:1) 1:1 POLOXAMER 188
PMPOL(1:2) 1:2 POLOXAMER 188
PMPOL(1:3) 1:3 POLOXAMER 188
B) Solvent Evaporation Method
Irbesartan and PVP K-30 were taken in ratio of 1:1, 1:2 and 1:3. The polymer was dissolved
in an adequate amount of methanol. Then add Irbesartan in to the solution under continuous
stirring. The solvent was then rapidly evaporated then sized into different sieve fractions and
stored.
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Formulation of Irbesartan solid dispersion
Formulation Code Drug : Carrier ratio Carrier
SEPVP(1:1) 1:1 PVP K 30
SEPVP(1:2) 1:2 PVP K 30
SEPVP(1:3) 1:3 PVP K 30
Evaluation of Solid Dispersion of Irbesartan
Physical Appearance
All the ratios of Irbesartan solid dispersions were evaluated for colour and appearance.
Drug Content
A quantity, which was equivalent to 80 mg of drug, was accurately weighed and transferred
to 100 ml volumetric flask. Then the volume was made up with water and Methanol (9:1) and
shaken for 10 min to ensure complete solubility of the drug. Then the solution was filtered
and filtrate was diluted suitably and Assayed for drug content at 250 nm by using UV-Visible
spectrophotometer.
In vitro dissolution study
The prepared solid dispersions were subjected to in vitro dissolution. Dissolution test was
carried out using USP Paddle method [apparatus 2]. The stirring rate was 50 rpm, pH-0.1 N
HCl was used as dissolution medium and dissolution medium was 0C.
Samples of 5 ml was withdrawn at regular intervals of time, filtered and replaced with 5 ml
of fresh dissolution medium, dilutions were made and analyzed for Irbesartan at 250 nm by
using UV-visible spectrophotometer.
Solid Dispersion Adsorbate of Irbesartan
Solid dispersion adsorbate by fusion method
Solid dispersions were prepared by weighed quantities of Irbesartan and Poloxamer 188 and
PEG4000. The Poloxamer 188 and PEG were molten in a porcelain dish at different
processing temperatures. Once homogeneous slurry was obtained, it was cooled rapidly at
different cooling temperatures and passed through number 22 sieves to obtain a uniform
particle size and stored in a desiccator at room temperature and evaluated. SDAs were
prepared similar to that of SD, but only difference was NUS was added after the preparation
of homogeneous slurry as that in SD.
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Formulation of Irbesartan solid dispersion with PEG4000 (Without Neusilin).
Formulation code Drug: carrier ratio Polymer
FEPEG (1:1) 1:1 PEG 4000
FEPEG (1:2) 1:2 PEG 4000
FEPEG (1:3) 1:3 PEG 4000
Formulation of Irbesartan solid dispersion adsorbate with PEG4000 (with Neusilin).
Formulation code Drug: carrier ratio Polymer
FENPEG (1:1) 1:1 PEG 4000
FENPEG (1:2) 1:2 PEG 4000
FENPEG (1:3) 1:3 PEG 4000
Formulation of Irbesartan solid dispersion with Poloxamer 188 (without Neusilin).
Formulation code Drug: carrier ratio Polymer
FEPOL(1:1) 1:1 Poloxamer 188
FEPOL(1:2) 1:2 Poloxamer 188
FEPOL(1:3) 1:3 Poloxamer 188
Formulation of Irbesartan solid dispersion adsorbate with poloxamer 188 (with
Neusilin).
Formulation code Drug: carrier ratio Polymer
FENPOL1:1 1:1 Poloxamer 188
FENPOL1:2 1:2 Poloxamer 188
FENPOL1:3 1:3 Poloxamer 188
Formulation Table for all batches.
BATCHES IRBESARTAN PVPK30 PEG4000 POLOXAMER 188 NEUSILIN
PMPVP(1:1) 100 100 - - -
PMPVP(1:2) 100 200 - - -
PMPVP(1:3) 100 300 - - -
PMPEG (1:1) 100 - 100 - -
PMPEG (1:2) 100 - 200 - -
PMPEG (1:3) 100 - 300 - -
PMPOL(1:1) 100 - - 100 -
PMPOL(1:2) 100 - - 200 -
PMPOL(1:3) 100 - - 300 -
SEPVP(1:1) 100 100 - - -
SEPVP(1:2) 100 200 - - -
SEPVP(1:3) 100 300 - - -
FEPEG (1:1) 100 - 100 - -
FEPEG (1:2) 100 - 200 - -
FEPEG (1:3) 100 - 300 - -
FENPEG (1:1) 100 - 100 - 100
FENPEG (1:2) 100 - 200 - 200
FENPEG (1:3) 100 - 300 - 300
FEPOL(1:1) 100 - - 100 -
FEPOL(1:2) 100 - - 200 -
FEPOL(1:3) 100 - - 300 -
FENPOL(1:1) 100 - - - 100
FENPOL(1:2) 100 - - - 200
FENPOL(1:3) 100 - - - 300
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Note:-All weight is in mg.
Characterization of Solid Dispersion Adsorbate of Irbesartan
Drug content
In vitro dissolution studies.
Fourier transform infrared spectroscopy
Differential scanning calorimetry
Statistical analysis
The U.S. FDA’s guidance for industry on dissolution testing of immediate release (IR) solid
oral dose forms (1997), as well as SUPAC-IR (1995), SUPACMR (1997) and bioavailability
and bioequivalence study guidance for oral dosage forms, describes the model independent
mathematical approach proposed by Moore and Flanner for calculating a dissimilarity factor
f1 and a similarity factor f2 of dissolution across a suitable time interval. The similarity factor
f2 is a measure of similarity in the percentage dissolution between two dissolution curves and
is defined by following equation,
f2=50×log {[1+ (1/n) Σt=1n (Rt-Tt) 2]-0.5 ×100}
Where,
n is the number of withdrawal points,
Rt is the percentage dissolved of reference at the time point t And
Tt is the percentage dissolved of test at the time point t.
MDT (mean Dissolution time)
A higher MDT value indicates a greater drug retarding ability. To understand the extent of
improvement in dissolution rate of FUR from its PMs and SDs with PEG and PVP, the
obtained dissolution data of all samples were fitted into the equation;
Where i is the dissolution sample number, n is the number of dissolution times, tmid is time at
the midpoint between times ti and ti-1, and ∆M is the amount of FUR dissolved (µg) between
times ti and ti-1.
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Formulation of the Tablet
Drug, SD of PEG (FEPEG 1:3) and Solid dispersion adsorbate of FENPEG (1:3) along with
all the excipients were accurately weighed and passed through 22 number sieves. Then the
powder was uniformly mixed in polybag. The resulting powder mixture was directly
compressed in to tablet using rotary tablet machine.
Formulation table of Tablet preparation from SD.
Ingredients (mg) Tablets of Pure
Drug
Tablets of
FEPEG (1:3)
Tablets of
FENPEG (1:3)
Irbesartan 150.00 -- --
SD of Irbesartan Eq. to 150 mg of Drug -- 600.00 600.00
MCC (Avicel 102) 579.00 129.00 129.00
Talc 7.00 7.00 7.00
Magnesium Stearate 14.00 14.00 14.00
Total 750.00 750.00 750.00
Characterization of Tablet
The prepared tablets were evaluated for weight variation, thickness, hardness, friability,
disintegration time, drug content analysis, and in vitro dissolution.
A. Weight Variation
B. Thickness
C. Hardness
D. Friability
E. Drug Content
F. Drug release study
G. Stability studies
RESULTS AND DISCUSSION
Preformulation Studies
Characterization of Drug
Results of Irbesartan characterization are given in below table.
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Characterization of Irbesartan.
Sr. No. Characteristic Properties Observation/Result
1 Organoleptic
Characteristics
Colour white to practically white fine
powder
2 Odour Characteristic odour
4
Flow Properties
Bulk density (g /ml) 0.45
5 Tapped density (g /ml) 0.51
6 Carr’s index (%) 16.48
7 Hausner’s ratio 1.07
8 Angle of repose (θ°) 58.08
9 Solubility Solubility Soluble in Methanol
Insoluble in water.
Based on above results it concluded that the API itself having good flow property because
Hausner ratio is 1.07. Further solubility found in methanol and water.
Ftir Study of Drug
The IR spectra of the drug showed their characteristic absorption bands which was given in
figure.
DSC Study of Irbesartan
The differential scanning calorimetric thermograms of the irbesartan are shown in below
figure 6.1.3. Irbesartan shows sharp endothermic peak at 189.12ºC which supports literature
data.
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Calibration Curve of Drug
Calibration Curve of Irbesartan
Overlay graph of Irbesartan at 210 nm in water:methnol (9:1).
Calibration curve of Irbesartan in water and methanol (1:9) at 210 nm.
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Phase Solubility
Phase solubility analysis has been among the preliminary requirements towards the
optimization of the development into inclusion complexes of the drugs as it permits the
evaluation of the affinity between different carriers and drug molecule in water. This process
has been used by many researchers for the determination of the exact molar ratios in which
the drugs could make complexes with different carriers.
Comparison of solubility for ratio of drug and different polymer.
Polymer Drug : Carrier ratio Increased solubility
PVPK-30 1:1 13 fold
PVPK-30 1:2 18 fold
PVPK-30 1:3 25 fold
Polymer Drug : Carrier ratio Increased solubility
Poloxamer 188 1:1 6 fold
Poloxamer 188 1:2 10 fold
Poloxamer 188 1:3 14 fold
Polymer Drug : Carrier ratio Increased solubility
PEG 4000 1:1 10 fold
PEG 4000 1:2 16 fold
PEG 4000 1:3 23 fold
Characterization of Solid Dispersion
Differential Scanning Calorimetry (Dsc) Analysis
DSC thermo gram of pure drug Irbesartan and solid dispersion of Irbesartan with PVPK 30,
Poloxamer 188 and PEG 6000 shown in below figure.6.5. Pure drug melting point was
observed 189.12°C. Different solid dispersion of Irbesartan with carriers shows melting point
of drug at 247.51°C in PVPK 30, 264.63°C in Poloxamer 188 and 256.35°C in PEG 4000.
Increased in melting point indicates that in such systems the drug has basically maintained its
original crystallinity.
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DSC thermogram of A. Drug, B. PMPVP, C. PMPEG and D.PMPOL.
Infrared (IR) Spectroscopic Analysis
Fourier transform infrared spectroscopy (FT-IR) has been used to assess the interaction
between drug and polymer in the solid state. The chemical interaction between the drug and
the carrier often leads to identifiable changes in the infrared (IR) profile of SD’s. However,
some of the changes are very subtle requiring careful interpretation of the spectrum.
The FTIR spectra of A. Drug, B. SD with PVPK 30, C. SD with Poloxamer 188 SD with
PEG 4000 and E. SD with Poloxamer 188 with Neusilin are shown in Figure 6.6.
FTIR of A. Drug, B. PMPVP, C. PMPEG and D. PMPOL E. FENPEG.
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X-Ray Powder Diffraction (Xrd)
The XRD spectra of pure drug Irbesartan and solid dispersion of Irbesartan with PVPK 30,
Poloxamer 188 and PEG 6000 are depicted in Figure 6.7. The diffraction spectrum of pure
Irbesartan indicated its crystalline nature as demonstrated by numerous peaks observed at 2θ
of 4.7, 12.5, 13.3, 17.1, 19.4, 21.2, 22.6, 23.2 and 27.3. Crystalline properties of PEG were
also confirmed by two peaks with the highest intensity at 2θ of 19.3 and 23.4.
XRD of A. Drug, B. PMPVP, C. PMPEG and D. PMPOL.
In-Vitro Dissolution Study
Drug release data of pure drug Irbesartan and prepared SD with PVPK 30, Poloxamer 188
and PEG 4000 shows in table 6.5. Based on that results, pure drug release only 9.40% after
60 min which was lowest drug release profile in all. Further in SD which was prepared by
physical method, no any significant improvement observed in drug release in all SD e.g.
PVPK 30, Poloxamer 188 and PEG 4000. Only 28% drug release observed in SD with PEG
by physical method. SD of solvent evaporation method and fusion method gives drastic
change in drug release after 60 min which was more than 80% in all SD’s. SD by fusion
method without neusilin gives 60% drug release in 30 min where with neusilin gives more
than 90% drug release in 30 min. So the neusilin gives significant impact on drug release with
SD’s.
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Comparison of Different solid dispersion of drug with PVPK 30, PEG 4000 and Poloxamer
188 gives in figures.
Drug Release of Irbesartan solid dispersion and solid dispersion adsorbate in 1 hour.
Batches 10 min 20 min 30 min 40 min 50 min 60 min
IRB 3.40 4.91 5.79 7.70 8.06 9.40
PMPVP(1:1) 4.40 5.92 6.03 8.70 9.20 10.15
PMPVP(1:2) 5.15 6.25 8.25 14.23 16.23 18.2
PMPVP(1:3) 5.65 7.49 10.90 17.91 18.97 21.64
PMPEG (1:1) 5.65 6.10 7.85 9.20 12.25 13.68
PMPEG (1:2) 5.76 8.34 12.64 15.65 20.11 23.22
PMPEG (1:3) 8.23 10.21 14.25 20.21 25.65 28.23
PMPOL(1:1) 5.42 6.01 7.42 8.25 11.25 12.01
PMPOL(1:2) 6.28 7.56 9.25 10.25 13.22 14.78
PMPOL(1:3) 7.00 8.25 11.20 12.59 15.99 17.76
SEPVP(1:1) 10.15 23.65 38.8 55.65 76.95 91.36
SEPVP(1:2) 16.68 25.74 42.36 57.73 81.05 92.49
SEPVP(1:3) 20.59 45.95 59.12 78.20 93.78 95.36
FEPEG (1:1) 15.69 26.46 41.87 57.73 78.14 90.96
FEPEG (1:2) 25.9 29.18 43.24 59.67 81.47 91.95
FEPEG (1:3) 27.75 39.17 57.32 65.18 89.7 91.30
FENPEG (1:1) 31.36 52.84 69.95 78.45 93.7 96.54
FENPEG (1:2) 38.79 64.67 81.85 89.49 90.54 92.65
FENPEG (1:3) 40.78 72.6 93.63 99.12 99.52 99.79
FEPOL(1:1) 13.15 24.95 39.68 55.35 76.34 89.50
FEPOL(1:2) 17.85 27.61 42.8 71.49 87.15 90.98
FEPOL(1:3) 22.45 39.19 69.64 84.41 91.74 96.10
FENPOL(1:1) 18.3 48.95 67.21 79.63 92.45 94.65
FENPOL(1:2) 24.5 54.59 82.78 91.37 93.65 96.47
FENPOL(1:3) 38.2 68.3 87.9 92.32 95.12 97.18
Drug Release of Irbesartan solid dispersion and solid dispersion adsorbate in 1 hour.
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Drug Release of Irbesartan solid dispersion and solid dispersion adsorbate in 1 hour.
Statistical Analysis
From the table 6.6 it is evident the release profile of IRB from all batches were different from
release profile of pure IRB. All batches showed difference in release profile of IRB compared
to Physical mixture method and solvent evaporation of IRB, respectively. FENPEG (1:3) and
FENPOL (1:3) which showed better in-vitro dissolution profile, lower MDT and f2 values.
% Drug dissolved within 30 minutes (DP30 min), f2 and mean dissolution time (MDT)
for pure Irbesartan and SD. Batches DP30 MDT(min) f2
IRB 5.79 14.12 -
PMPVP(1:1) 6.03 13.12 97.96
PMPVP(1:2) 8.25 16.12 75.86
PMPVP(1:3) 10.90 15.91 68.54
PMPEG (1:1) 7.85 14.99 87.94
PMPEG (1:2) 12.64 16.54 67.3
PMPEG (1:3) 14.25 16.08 59.86
PMPOL(1:1) 7.42 14.03 92.19
PMPOL(1:2) 9.25 14.28 83.14
PMPOL(1:3) 11.20 14.5 75.26
SEPVP(1:1) 38.8 18.76 29.9
SEPVP(1:2) 42.36 17.19 28.93
SEPVP(1:3) 59.12 15.11 24.92
FEPEG (1:1) 41.87 17.91 29.39
FEPEG (1:2) 43.24 16.97 28.47
FEPEG (1:3) 57.32 14.93 26.33
FENPEG (1:1) 69.95 11.87 23.97
FENPEG (1:2) 81.85 14.56 21.88
FENPEG (1:3) 93.63 9.63 20.88
FEPOL(1:1) 39.68 18.29 30.09
FEPOL(1:2) 42.8 16.43 27.48
FEPOL(1:3) 69.64 14.62 24.47
FENPOL(1:1) 67.21 14.67 27.91
FENPOL(1:2) 82.78 12.71 25.42
FENPOL(1:3) 87.9 11.08 24.04
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Drug Content
Prepared formulations were checked for drug content analysis and the obtained results were
recorded in table 6.7. From the results it concluded that there was no any loss of drug in SD
preparation. All batches having drug content data well within acceptable range.
Drug content results.
Batches % Drug Content
IRB 99.4 ± 0.4
PMPVP(1:1) 98.5 ± 0.5
PMPVP(1:2) 99.5 ± 0.7
PMPVP(1:3) 97.8 ± 0.5
PMPEG (1:1) 99.8 ± 0.6
PMPEG (1:2) 99.4 ± 0.5
PMPEG (1:3) 98.4 ± 0.4
PMPOL(1:1) 99.4 ± 0.2
PMPOL(1:2) 98.8 ± 0.4
PMPOL(1:3) 99.7 ± 0.2
SEPVP(1:1) 99.9 ± 0.6
SEPVP(1:2) 99.8 ± 0.4
SEPVP(1:3) 99.4 ± 0.5
FEPEG (1:1) 99.7 ± 0.7
FEPEG (1:2) 98.7 ± 0.5
FEPEG (1:3) 97.9 ± 0.6
FENPEG (1:1) 98.9 ± 0.4
FENPEG (1:2) 99.7 ± 0.5
FENPEG (1:3) 99.6 ± 0.6
FEPOL(1:1) 98.7 ± 0.4
FEPOL(1:2) 99.6 ± 0.8
FEPOL(1:3) 98.7 ± 0.5
FENPOL(1:1) 99.5 ± 0.5
FENPOL(1:2) 98.9 ± 0.3
FENPOL(1:3) 99.8 ± 0.4
Evalution of Tablets.
Parameters Tablets of Pure Drug Tablets of FEPEG
(1:3)
Tablets of FENPEG
(1:3)
Hardness 3.5 ± 0.42 3.7 ± 0.34 3.9 ± 0.23
Friability 0.41± 0.05 0.40 ± 0.03 0.35 ± 0.01
Disintegration Time (min) 4.5 ± 0.62 4.1 ± 0.32 4.3 ± 0.51
% Drug Content 98.3 ± 0.45 97.5 ± 0.12 99.3 ± 0.35
% Drug release at 60 min 10.9 ± 0.10 91.5 ± 0.44 99.5 ± 0.17
Stability Study
Stability study of Optimized batch FENPEG (1:3) tablets performed for 1 month. Sample
withdrawal after 1 month; it showed no change in in-vitro drug release profile. Results of
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Yadav et al. World Journal of Pharmacy and Pharmaceutical Sciences
stability study do not show any remarkable change in the release profile of the tablet after the
stability.
ACKNOWLEDGEMENT
The authors are also thankful to Saraswati Institute of Pharmaceutical Sciences for providing
necessary equipment, facility & chemicals to complete research work.
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