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Vol 7|Issue 1| 2017|1-11.
1 | P a g e
Asian Journal of Pharmaceutical Science & Technology
e-ISSN: 2248 – 9185 www.ajpst.com Print ISSN: 2248 – 9177
HYDROXY PROPYL Β-CYCLODEXTRINE AS A CARRIER FOR
IMPROVEMENT OF DISSOLUTION RATE AND SOLUBILITY OF
POORLY SOLUBLE FELODIPINE USING SPRAY DRYING
TECHNIQUE
Ravindranath S. Misal* and Vijay R. Mahajan
Department Of Pharmaceutics, SMBT College of Pharmacy, Nandi Hills Dhamangaon, Nashik-422403, Maharashtra, India.
ABSTRACT
The aim of the present research work is to prepare a formulation by using hydroxy propyl β-cyclodextrin as a solubility
enhancer carrier for improvement of dissolution rate and solubility of poorly soluble felodipine using spray drying technique.
Spray drying technique is one of the most widely and successfully used method for improvement dissolution rate and
bioavailability of poorly soluble drugs. The material used to prepare formulation such as Drug (felodipine) and polymers like
(Hydroxy propyl β-cyclodextrin and Aerosil 200) was prepared in three different ratios 1:1:1, 1:1.5:1.5 and 1:2:2. Then all above
ratio evaluated for solubility study, percent drug content and in vitro drug dissolution study. Then drug alone and its solid
dispersion spray dried powder studied for their physicochemical properties like FTIR, DSC, PXRD and SEM. Then result of final
formulation is observed for percent drug release of SD1 shows 97.59% release and percent drug content SD1 shows
(98.73±0.199%) as a compared with pure drug. Then stability study of final product was determined at three different temperature
at (-4°C, 25°C and 40°C) shows drug is compatible with excipient, no chemical reaction and physical changes occur, so final
spray dried formulation is stable form after 3 month. The formulation was prepared, characterized and evaluated by various
studies and conclude that pure drug is solubilised in spray dried powder which is formed by spray drying technique. By using
HBC (hydroxyl propyl β-cyclodextrin) the guest-host type powder formulation is formed between the drug and the non polar
cavity in the HBC that results in enhanced solubility and dissolution rate of absorption after oral administration.
Key words: Poorly soluble, Highly permeable BCS class-II drugs, Solubility, Dissolution rate, Spray drying technique.
INTRODUCTION
The solubility concept is very important for
enhancing or improving oral route of 40% new BCS class-II
drug substances. Solubility is defined as concentration of
the dissolved solid (the solute) in the solvent medium,
which becomes saturated with solute and is in equilibrium
with the solute at a defined pH, temperature and pressure
[1]. So here drug using felodipine is poorly soluble and
highly permeable BCS class-II drug candidate, were using
suitable carrier system for improvement of solubility as well
as dissolution rate of felodipine with carrier like e.g. Hβ-
Cyclodextrin and Aerosil 200. The various method used to
enhancement of felodipine like Complexation, spray drying
technique, solid dispersion, solvent evaporation method,
particle size reduction, supercritical fluid extraction method.
Instead of all solubility enhancement method, here choosen
spray drying technique for preparing of solid dispersion.
The felodipine chemically is 4-(2,3-Dichlorophenyl)-1,4-
dihydro-2,6-dimethyl-3,5 pyridine dicarboxylic acid ethyl
methyl ester, Off-White slightly pale yellowish crystalline
powder and used in the treatment of hypertension and
anginal attack.
The therapeutic effect of this group of drugs is
believed to be related to their specific cellular action of
selectively inhibiting transmembrane influx of calcium ions
into cardiac muscle and vascular smooth muscle. The
contractile processes of these tissues are dependent upon the
movement of extracellular calcium into the cells through
specific ion channels. Felodipine blocks transmembrane
Corresponding Author: Ravindranath S. Misal E-mail: misalravindranath@gmail.com
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influx of calcium through the slow channel without
affecting to any significant degree the transmembrane influx
of sodium through the fast channel. This results in a
reduction of free calcium ions available within cells of the
above tissues. Felodipine does not alter total serum calcium.
In vitro studies show that the effects of felodipine on
contractile mechanisms are selective, with greater effects on
vascular smooth muscle than on cardiac muscle. Negative
inotropic effects can be detected in vitro, but such effects
have not been seen in intact animals [2, 3]. By using spray
drying technique preparing a solid dispersion formulation
with controlled parameter and then evaluating for solubility
study, in vitro drug release study, drug content,
compatibility study, and solid state characterization like
FTIR, DSC, SEM and PXRD. Finally formulation was
taken for stability study at various temperatures for 3
month, after three month further studying by visual
assessment, percent drug content, in vitro drug release and
FTIR, so conclude that system is stable. In spray drying
method the drug is dissolved in suitable solvent and the
required amount of carrier is dissolved in water. Solutions
are then mixed by sonication or other suitable method to
produce a clear solution, which is then spray dried using
spray dryer [4].
MATERIAL AND METHOD
Materials
Felodipine was procured from Astra Zeneca Pvt
Ltd (Mumbai), India. HP β-cyclodextrine, were laboratory
grade (Fine chem. Lab industries). All other chemicals used
were of analytical grade.
Preparation of solid dispersions of Felodipine
Preparation of physical mixture
Physical mixtures were prepared by mixing of
Felodipine, HP β cyclodextrin and carrier system (Aerosil
200) in mortar and pestle by geometric dilution method. The
mixture is then passed through sieve 60 µm. all mixtures
were prepared by same process as shown in table no.2 [5,
6].
Preparation of SD by spray drying technique
The Felodipine drug and the carriers ( HP β
Cyclodextrin: Aerosil 200) were weight accurately in
different ratios and then dissolved in appropriate quantity of
methanol. Finally both the solutions were mix well using
glass rod to obtain a white dispersed solution. Sprays drying
of this solution were performed using laboratory-scale spray
dryer (Spray Mate, JISL) under the following set of
conditions in table no.2 and process overview of spray
drying technique is shown in figure no.1. Each solid
dispersion batch was prepared in duplicates employing each
carrier in variable proportions, i.e. 1:1:1, 1:1.5:1.5, 1:2:2
w/w. The dispersions were subsequently desiccated under
vacuum for 48 hrs [7, 8].
Melting point determination
Melting point of felodipine was determined by
taking a small amount of sample in capillary tube sealed at
one end and placed in beaker filled by liquid paraffin in
melting point apparatus. The melting point was noted and
readings were taken in triplicate. The mean standard
deviation (SD±mean) of felodipine was done by statistical
analysis method [9].
UV Spectroscopy
Stock solution (10mg/100ml) of Felodipine was
prepared in methanol. Further dilution of stock solution was
prepared to obtained suitable concentration. The UV
Spectrum in the range of 200-400 nm on Thermo-fisher
UV-2600 double beam spectrometer. The wavelength of
maximum absorption (ƛmax) was determined.
Calibration curve of Felodipine in methanol
Calibration curve of Felodipine was done by using
UV- spectrophotometer (Thermo-fisher UV-2600) was
weighed Felodipine accurately 10mg and dissolved in
100ml methanol to make a 100µg/ml stock solution. Then
prepare a concentration 2, 4, 6, 8, and 10µg/ml respectively.
Similarly Calibration curve of felodipine was given in pH
6.8 phosphate buffer containing 0.15% tween 80 [10].
Phase-solubility studies
Solubility measurements were performed in
triplicate. An excess quantity of the Felodipine and solid
dispersions were dissolved in 10ml of distilled water. The
flasks were capped tightly and sonicate for 2 hours and left
a side for overnight. After that the solutions were filtered by
0.45Lm filter paper and analyzed by UV spectrophotometer
(Thermo-fisher UV-2600) at 361nm. The mean standard
deviation (SD±mean) of felodipine was done by statistical
analysis method [11-14].
Compatibility study Drug-excipient compatibility study was done for
four week and samples are visual observed initially, four
week for any color change. The visual observation shows
that there was no colour change observed during storage for
four week [15, 16].
Drug Content The percentage drug content in SD spray dried
powder were estimated by dissolving quantities equivalent
to 10 mg of powder in 10 ml methanol, vortex for 10 min
and filtered through 0.45μm membrane filter, appropriately
diluted with distilled water and the UV absorbance were
recorded at 361 nm by using UV-visible spectrophotometer
(Thermo-fisher UV-2600). The mean standard deviation
(SD±mean) of felodipine was done by statistical analysis
method [17, 18].
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In-vitro dissolution studies
Drug release studies were performed in triplicate
on USP type II apparatus (ELECTROLAB TDT-08L
Dissolution tester apparatus USP) for 45 min in pH 6.8
phosphate buffer containing 0.15% tween 80 at 50rpm
speed and dissolution medium 900ml. The temperature was
maintained at 37±1°C, solid dispersions equivalent to 10mg
of Felodipine were taken. The aliquots were taken at the
particular interval of time (5, 10, 15, 20, 25, 30, 35, 40,
and45 min respectively) and analyzed for absorbance using
UV-spectrophotometer (Thermo-fisher UV-2600) at 361nm.
10 mg of pure drug was also treated in the same manner and
the results of pure drug and solid dispersions were
compared. The reading of all formulation recorded triplicate
and calculate for standard deviation of each formulation as
well as pure drug by statistical analysis method [19-21].
Characterization of Spray Dried Solid Dispersed
Powder
Percent yield of spray dried product
The percentage of production yield of solid
dispersion of spray dried powder was calculated using the
weight of the final product after drying with respect to the
initial total weight of the drug and polymer used for the
preparation of solid dispersion. The percentage yield of
SD1, SD2 and SD3 was calculated by using following
formula;
Powder flow properties Spray dried product was evaluated for bulk density,
Tap density, Compressibility index, Hausner ratio and
Angle of repose [9].
Bulk Density Bulk density of Solid dispersion was determined
by pouring gently 13.60 gm of SD1 through a glass funnel
into a 25ml granulated cylinder. The volume occupied by
the sample was recorded. The bulk density was calculated
by using following formula;
Tapped Density Tapped density of solid dispersion was determined
by pouring gently 13.60 gm of SD1 through a glass funnel
into a 25ml granulated cylinder. The cylinder was allowed
to fall on to a hard surface form a height of 14mm+2mm at
the rate of 300 drops/min for 500 taps, note the volume, and
then give additional 750 taps and again note the volume. If
the difference between two volumes is more than 2% give
additional 1250 taps. The tapping was continued till there is
n no volume change or it is below 2% in two successive
tapping.
Carr’s Compressibility Index (CI)
The compressibility index of the powder blend was
determined using carr’s compressibility index as shown in
following formula;
Hausners Ratio Hausner ratio was calculated by following formula;
Angle of Repose The angle of repose of the powder blend was
determined by using funnel method. The height of the
funnel was adjusted in such a way that the tip of the funnel
just touched the apex of the heap of the powder. The
diameter of the powder cone was measured and angle of
repose was calculated by using the equation;
Where, h-height of the powder cone and
r-radius of base of powder cone
Solid State Characterization
Fourier transforms Infrared spectroscopy (FTIR)
Fourier transform infrared (FTIR-Shimadzu8400s)
spectroscopy was employed to characterize further the
possible interactions between the drug and the carrier in the
solid state on a FTIR spectrophotometer by the conventional
KBr pellet method. The spectra were scanned over a
frequency range 4000-400 cm-1 [11, 14].
Differential Scanning Calorimeter (DSC)
The possibility of any interaction between the drug
and the carriers during preparation of Physical mixture of
solid dispersion was assessed by carrying out thermal
analysis of drug and spray dried solid dispersion using DSC.
DSC analysis was performed using (DSC Shimadzu
Instrument, DSC-60 Japan) on 4 mg samples. Samples were
heated in an open aluminum pan at a rate of 20°C/min
conducted over a temperature range of 50 to 500°C under a
nitrogen flow of 50 mL/min.
X-ray powder diffractometer (PXRD)
By using PXRD is to determine the powder
characteristics, X-ray powder diffraction studies of drug
alone and spray dried solid dispersion was performed. X-ray
powder diffraction patterns were recorded on BRUKER, D8
Advance (Germany) BRUKER, source-2.2 KW Cu Anode,
Dermic x-ray tube, detector-Lynux eye detector, Beta filter-
Ni filter and Sample holder- Zero bachground /
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PMMA(Germany) diffractometer at following condition:.
The scanning rate employed was 6.0000° min–1
over
10.3200 to 47.7658° at 25°C temperature with Targeted
Current voltage (Cu-30mA at 40kv) diffraction angle (2θ)
range [17, 19].
Scanning electron microscopy (SEM)
The morphological feature of particle of Felodipine
and Solid dispersion (spray powder) were investigated by
scanning electron microscopy (SEM). The samples were
fixed on a brass stub using double sided adhesive tape and
were made electrically conductive by coating (by gold ion)
in vacuum (6Pas) with platinum (5-6 nm/min) using JEOL-
5400 (JAPAN) Ion Sputter (E-1030) at 15 mA. The SEM
images were analyzed with an image analysis system
(Image inside Ver.2.32) for particle morphology and size
voltage of 10kv [3, 10].
Stability study Three month stability study of solid dispersion
(Spray dried powder) at Freeze Temperature (-4°C), Room
Temperature (25°C) and High Temperature (40°C) was
carried. 5gm of solid- Spray dried powder formulations was
placed in glass vial and seal vial was placed at different
temperature condition and each sample is visually observed
at interval of each month for any colour change and after 3
month samples were analyzed by FT-IR. FT-IR of the solid-
spray dried powder after 3 months was compared with the
FT-IR of pure drug for identification of any change in the
drug during stability study. Also drug content and in-vitro
drug release of solid dispersion (spray dried powder) was
determined after 3 month [19, 20].
RESULT AND DISCUSSION
Pre-formulation Data The preformulation study of felodipine was done
by conducting their Organoleptic characteristic, melting
point, calibration curve spectra (ƛmax), solubility study of
drug respectively. Results are shown in following table
no.3.
UV Spectroscopy UV spectra of felodipine were observed at (ƛ359
nm) maximum wavelength and results are shown in table
no.3 and figure no.2.
Calibration curve of Felodipine in methanol and pH 6.8
phosphate buffer Calibration curve of Felodipine was done by UV
spectroscopy and result are shown in Table no.4, 5 and
figure no.3, 4 respectively. The regression coefficient of
felodipine in methanol and phosphate buffer was found to
be 0.9968 and 0.9974 at ƛmax 359 nm and 362.5nm
respectively.
Solubility study of Felodipine API and solid dispersion
of Spray dried powder
The solubility study of active
pharmaceutical ingredient (Felodipine) and solid dispersion
of spray dried powder was done by shake flask method in
different solvent and then determined by UV spectroscopy
at wavelength ƛmax 359 nm and result are shown in table
no.6, 7 and figure no. 5, 6 respectively.
Compatibility study
Drug excipient compatibility study of (SD1, SD2
and SD3) was determined by visual assessment method and
concludes that no physical changes or colour change
observed after four weak at room temperatures and result
are shown in table no.8 [6].
Drug content
The drug content of felodipine formulation was
determined by UV-Spectrophotometer and conclude that
spray dried powder of ternary solid dispersions showed the
presence of high drug content. It indicates that the drug is
uniformly dispersed in the powder formulation. The percent
drug content spray dried powder is shown in table no.9.
[21].
In vitro drug release study
The percent drug release profile of Felodipine
(Active pharmaceutical ingredient) and Spray dried solid
dispersion ratio (1:1:1, 1:1.5:1.5 and 1:2:2) was done by
paddle type dissolution apparatus II and result reveled that
spray dried formulation (SD1-1:1:1) shows 97.59% w/w
drug release in 45 min more than other formulation (SD2-
93.47% and SD3-91.99% w/w in 45 min) and API shows
percent drug release 69.52% w/w in 45 min. So that ratio
1:1:1 was selected for further study and result is shown in
table no.10 and figure no.7 [11,13].
Characterization Of Spray Dried Solid Dispersed
Powder
The Physical mixture of (SD1, SD2 and SD3) was
prepared in methanol to form a white dispersion and it is
spraying by using spray dryer to from fine particle powder.
Then powder was evaluated for percent yield recovery and
powder flow properties and result shown in Table no. 11
and 12 [3, 7, 10].
Percent yield of spray powder
The percent yield of spray dried powder was
calculated and result is shown in table no.11.
Flow properties
The spray powder was evaluated by, bulk density,
tapped density, carr’s index, hausner’s ratio and angle of
repose and results are shown in table no12.
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Solid State Characterization
FT-IR (Fourier transforms Infrared spectroscopy)
spectrum FTIR spectrum of the drug sample showed all the
characteristic IR peaks as reported in the literature
indicating the presence of functional groups of Felodipine.
FT-IR spectra mainly used to determine if there is any
interaction between the drug and any of the excipients. The
presence of interaction is detected by the disappearance of
important functional group of the drug. The pure felodipine
(figure no.8) showed the characteristic peaks at wave
numbers of (at 1500.67, 1701.27, 1790, 3097.78, 3371.68)
confirming the drug structure. The spectrum of felodipine
and Hβ- cyclodextrine spray powder (SD1) also shows
characteristic peaks (at 1458.23, 1732.13, 2928.04 and
3387.11) in figure no.9 for felodipine indicating no
interaction between the drug and excipient. This indicating
the no chemical interaction in the mixture that the molecular
structure of felodipine remained completely intact. Then
finally conclude that felodipine not interact any excipient.
The complete specification of comparison between
felodipine and spray powder with Typical IR bands (cm-1
)
spectral peaks was given in table no.13. are as follows.
DSC (differential scanning calorimeter)
The DSC thermogram of pure Felodipine exhibited
a sharp endothermic peak at145.08oC with onset at
140.08°C and recovery at 151.29°C. The sharp endothermic
peak of felodipine shown in figure no.10. The DSC of solid
dispersion of spray dried powder not shows any sharp
melting peak of Felodipine. The absence of sharp melting
peak of Felodipine in the range of 140.08-151.29oC in the
DSC of Solid dispersion of spray powder (SD1) in figure
no.11 indicate that the Hβ-Cyclodextrine inhibited the
crystallization of Felodipine i.e. felodipine is in crystalline
form or in (amorphous nature) solubilized form in solid
dispersion [3, 6].
PX-RD (X-ray powder diffraction) The X-ray diffraction spectra of felodipine powder
showed sharp distinct peaks indicating presence of high
crystalline state. From the X-Ray diffraction profile, the
characteristic felodipine peaks with high intensity were
found to be 2θ at 10.3200o, 14.6029
o, 16.6029
o, 21.900
o,
22.1000o, 23.5169
o, 25.3200
o, 26.9150
o, 31.1549
o,
32.2547°, 35.0600°, 40.2780°, 44.5512° and 47.7658o in
figure no.12. The XRD pattern of solid dispersion of spray
powder sample SD-1 exhibited all the characteristic
diffraction peaks of felodipine with lower intensity. This
study revealed that the crystallinity was reduced to a certain
extent in the solid dispersion form. Intensity of peak
sharpness was reduced in solid dispersion compared to pure
drug. Various studies have shown that Hβ-Cyclodextrine
decreased crystallinity of drugs and resulting in amorphous
nature of drug in the solid dispersions of final spray powder
product in figure no.13 [18].
SEM (Scanning electron microscopy)
Scanning electron microscopy (SEM) was
used to determine the particle morphology of pure drug and
optimized solid dispersion. The SEM of Felodipine
(14a,14b) and solid dispersion of spray powder (14c, 14d)
was done and results are shown in figure 14. Figure 14
revealed that Felodipine present as crystalline powder with
rectangular plate shaped crystals. The solid dispersion of
spray powder shows irregular shaped granular particle.
SEM of the Solid dispersion of spray dried powder does not
show any rectangular crystals of drug (Felodipine) on the
surface of H beta cyclodextrin, the shape of formulation is
spherical and somewhat smooth. It indicates that drug is
present in the soluble form in Hβ-cyclodextrine and aerosil
200 (spray dried powder formulation), which absorbed on
the surface of Hβ-cyclodextrine and aerosil 200 [5].
Stability Study
Stability of spray dried final powder was done by
visual assessment method, FTIR spectroscopy method and
in vitro dissolution study at -4°C, 25°C and 40°C for 3
month respectively. All results are shown in following
tables.no. 14,15,16.
Visual assessment
Visual assessment of spray dried powder
shows no any colour or physical characteristic changes, so
final spray dried formulation is stable at -4°C, 25°C and
40°C respectively. Result is shown in following table no14.
FTIR Spectroscopy
The stability study of spray dried product after 3
month was determined by FTIR spectroscopy at -4°C, 25°C,
40°C and shows no any functional group change, result are
shown in figure no.15.
In vitro drug release study The stability study of felodipine spray dried
powder was done by in vitro dissolution test apparatus
(paddle type II) and result are shows after 3 month at -4°C
(97.95%), 25°C(97.53%) and 40°C(96.96%) within 30 min
respectively, Table no.15 and figure no16.
Percent drug content
The percent drug of spray dried powder was
determined by stability strudy at three different temperature
(-4°c, 25°c and 40°c) after 3 month and result are shown in
table no.16 and figure no.17.
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Table 1. Parameter of spray drying techniques
Sr. No. Parameter Optimized Value
1 Inlet Temperature 55°C
2 Out Temperature 35°C
3 Aspiration Speed 1400rpm
4 Compressed Air Flow Rate 2.5 Bar
5 Feeding Rate 5ml/min
Table 2. Preparation of physical mixture
Method Felodipine : HP β-CD: Aerosil 200 Formulation name
Spray Drying Method
1:1:1 SD1
1:1.5:1.5 SD2
1:2:2 SD3
Table 3. Preformulation observed data of felodipine
Sr no. Parameter Reference Observed
1 Organoleptic characteristic
A Colour off white or pale yellowish powder off white or pale yellowish powder
B Odour Odourless Odourless
C Appearance Solid crystalline powder Solid crystalline powder
2 Melting point 142-145°C 144.33±0.33°C
6 ƛ max 360 nm 359 nm
Table 4. Absorbance of felodipine in methanol at ƛ 361 nm
Sr.no. Concentration Absorbance
1 2 0.100
2 4 0.175
3 6 0.287
4 8 0.365
5 10 0.483
Table 5. Absorbance of felodipine in ph 6.8 phosphate buffer
Sr.no. concentration Absorbance
1 2 0.068
2 4 0.123
3 6 0.197
4 8 0.277
5 10 0.345
Table 6. Solubility data of felodipine in different solvent
Solvent Solubility mg/ml at 25°C Concentration μg/ml at 25°C
Distil water 0.001701±0.011 17.01±0.011
Methanol 0.01630±0.015 163.0±0.015
Ethanol 0.01626±0.011 162.6±0.011
Acetone 0.01623±0.023 162.3±0.023
0.1 N HCL 0.001936±0.0202 19.36±0.202
Phosphate buffer 0.003100±0.012 31.00±0.012
Table 7. saturated solubility study of spray dried solid dispersion (SD1, SD2 and SD3)
Felodipine:HP β-Cyclodextrine: Aerosil 200 Solubility in µg/ml
Water pH 6.8 phosphate buffer (0.15% tween 80)
SD1 44.90±0.015 81.01±0.0295
SD2 38.12±0.037 69.27±0.030
SD3 33.78±0.012 65.00±0.026
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Table 8. compatibility study of ternary phase solid dispersion of (SD1, SD2 AND SD3)
Weak Physical Mixture Initial observation Final observation
1
SD1, SD2, SD3
White, Fine powder No change
2 White, Fine powder No change
3 White, Fine powder No change
4 White, Fine powder No change
Table 9. percent drug content of different formulation
Formulation Code Drug Content (% w/w) Mean Drug Content (% w/w)
SD1
98.67
98.73±0.199 98.43
99.11
SD2
97.12
96.97±0.128 96.72
97.09
SD3
93.23
93.52±0.570 92.72
94.63
Table 10. In vitro drug release profile of drug and three spray dried powder ratio
Time
% Drug Release
API SD 1 SD 2 SD 3
5 11.30±0.046 25.65±0.065 18.13±0.11 17.11±0.081
10 18.06±0.049 33.43±0.017 27.99±0.21 25.25±0.022
15 24.76±0.043 40.31±0.097 37.15±0.070 32.12±0.047
20 32.98±0.053 47.13±0.087 46.38±0.045 45.05±0.022
25 39.87±0.058 54.92±0.038 53.46±0.032 51.78±0.055
30 47.77±0.040 63.76±0.077 61.68±0.13 59.33±0.043
35 54.22±0.034 70.72±0.019 69.39±0.11 67.90±0.019
40 60.23±0.042 83.11±0.031 78.87±0.089 77.23±0.070
45 69.52±0.013 97.59±0.024 93.47±0.067 91.99±0.010
Table 11. Percent yield of final three formulation
Solvent Formulation Weighed quantity in gm Total weight in gm Recovered weight
(gm)
Percent
yield %
150 SD1 5:5:5 15 13.60 90.66
200 SD2 5:7.5:7.5 20 17.25 86.25
250 SD3 5:10:10 25 22.13 88.52
Table 12. Result of flow properties of spray dried product
Sr. No. Parameter Result Inference
1 Bulk Density 0.5093 g/ml --------
2 Tapped Density 0.6098 g/ml --------
3 Compressibility Index 16.48 Good
4 Hausner Ratio 1.1973 Good
5 Angle of Repose 33.66 Passable
Table 13. FT-IR interpretation comparison of drug and spray powder (SD1)
Typical IR bands (cm-1
) API Interpretation SD1 Interpretation
-N-H-stretching 3371.66 3387.11
=C-H-stretching 3097.78 -
C-H-Stretching 2955.93 2928.04
-C-O-stretching ester 1701.27 1732.13
-C=C-(skeleton vibration of aromatic ring stretching) 1500.67 1458.23
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Table 14. Stability study of final spray dried powder by visual assessment method
Table 15. Stability of felodipine spray dried powder by in vitro drug release study
Sr.no. Time in min % Drug release after 3 month
-4°C 25°C 40°C
1 5 26.03±0.008 25.51±0.23 25.27±0.123
2 10 34.22±0.017 34.89±0.15 33.75±0.005
3 15 40.44±0.023 40.82±0.059 39.68±0.014
4 20 48.00±0.012 47.11±0.011 48.67±0.003
5 25 55.43±0.027 54.1±0.037 55.24±0.009
6 30 61.23±0.004 60.02±0.05 59.97±0.11
7 35 71.92±0.011 70.22±0.08 70.03±0.053
8 40 83.87±0.019 82.92±0.0043 82.54±0.06
9 45 97.57±0.146 97.53±0.001 96.96±0.010
Table 16. Percent drug content of spray powder by stability study
Formulation code Temperature Drug content (%w/w)
SD1
-4°c 98.23±0.011
25°c 98.17±0.009
40°c 99.07±0.019
Fig 1. Overview of spray drying method
Fig 2. Scanning UV spectra of felodipine at ƛ359 nm
Fig 3. Calibration curve of Felodipine in methanol
Fig 4. Calibration curve of Felodipine in pH 6.8 phosphate
buffer
Fig 5. The graphical representation of solubility study in
different solvent
Fig 6. Diagram of solubility study of spray dried powder
month Temperature Final product Initial observation Final observation
1 -4°C
SD1
White, Fine powder No change
2 25°C White, Fine powder No change
3 40°C White, Fine powder No change
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Fig 7. Diagram of percent drug release graph
Fig 8. FT-IR Spectra of Felodipine
Fig 9. FT-IR of solid dispersion by spray dried powder
(SD1)
Fig 10. DSC spectra of felodipine
Fig 11. DSC spectra of SD1
Fig 12. PX-RD thermogram of API
Fig 13.PX-RD thermograms of SD1
Fig 14. Particle size characteristic of felodipine and spray
powder by SEM
14a. API
14b. API
14c. SD1
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14d. SD1
Fig 15. FTIR compatibility of solid dispersion after three
month at -4°c, 25°c and 40°c
Fig 16. Graphical presentation of % drug release data by
stability study after 3 month
Fig 17. Diagrammatic presentation of % drug content
determined by stability study
CONCLUSION The solid dispersion of (Felodipine: Hβ-
cyclodextrin: Aerosil 200) formulation was prepared by
spray drying technique using suitable solvent system
(methanol). The ratio of system (1:1:1) was shows high
solublility then other formulation, so increasing its
dissolution rate. The drug-excipient compatibility shows no
any colour change in all physical mixture after 4 weak at
room temperature. Then percent drug content of SD1
(98.73±0.199) shows more drug content than other
formulation. Then determine the In vitro drug release study
shows more release (97.59% after 45min) then other
formulation. The final formulation was evaluated for solid
state characterization such as DSC, SEM, FTIR and PXRD
in spray dried powder. DSC of solid dispersion shows
absence melting peak in the range of 140.08-151.29oC.
Finally stability study of final product was determined by
evaluating visual method (colour remain constant no
change), in vitro drug release study (-4°c [ 97. 57 % ],
25°c[97.53%], 40°c[96.96%] shows after 3 month and FTIR
spectroscopy (no change in FTIR peak after 3 month at
different temperature). The percent drug content of final
formulation shows at different temperature (-4°c[98.23%],
25°c[98.17%] and 40°c[99.07%] after 3 month. The
felodipine spray powder was formulated, evaluated and
conclude that increase in dissolution rate as well as increase
oral solubility of felodipine solid dispersion by preparing
spray drying technique.
ACKNOWLEDGEMENT
The author is thankful to SMBT College of
pharmacy, Dhamangaon, Nashik for carrying out the
M.Pharmacy II Year project and for providing the library
with internet facilities to vast literature study for the project
to carry out the research work. The author is thankful to
Astra Zeneca-pvt. Ltd. Mumbai for providing free gift
sample for research work.
CONFLICT OF INTEREST:
The authors declare that they have no conflict of interest.
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