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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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