Int J Curr Pharm Res, Vol 8, Issue 2, 52-60 Original Article


FORMULATION AND EVALUATION OF ANTIDEPRESSANT ORODISPERSIBLE TABLETS

P. SIREESHA*1, R. KIRANJYOTHI1

Department of pharmaceutics, Oil Technological Research Institute, Anantapuram, A. P 515001
Email: sireesha.panditha@gmail.com

Received: 25 Jan 2016, Revised and Accepted: 20 Mar 2016

ABSTRACT

Objective: Orodispersible tablet formulation was proposed to be developed for fluoxetine hydrochloride taking into consideration it’s physical, chemical, pharmacological and pharmacokinetic properties and was proposed to be investigated with respect to its potential to be developed into novel drug delivery system

Methods: Carrying out pre-formulation studies such as drug-polymer interaction analysis by Fourier Transform Infrared (FTIR) spectroscopy and pre-compression characterization of a physical mixture of drug and excipients. Preparation of the orodispersible tablet by using various super disintegrants like croscarmellose, crospovidone & sodium starch glycolate. Preparation of the orodispersible tablet by using various methods like wet granulation method & sublimation method.

Results: To evaluate tablets for various physicochemical parameters such as hardness, friability, weight variation, drug content, wetting time, in vitro disintegration time, in vitro dissolution.

Conclusion: Finally concluded that the oro dispersible tablet of fluoxetine hydrochloride formulated by sublimation method by using crospovidone at 4.5% level used for depression treatment.

Keywords: Fluxetine, orodispersible tablets, Crosscarmellose, Crospovidone, Sodium starch glycolate

© 2016 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

INTRODUCTION

The performance of ODTs depends on the technology used in their manufacture. The orally disintegrating property of these tablets is attributable to the quick ingress of water into the tablet matrix, which creates porous structure and results in rapid disintegration [1, 2]. Hence, the basic approaches to develop ODTs include maximizing the porous structure of the tablet matrix, incorporating the appropriate disintegrating agent and using highly water-soluble excipients in the formulation. Fluoxetine hydrochloride is the first agent of the class of antidepressants known as selective serotonin-reuptake inhibitors (SSRIs) [3]. Despite distinct structural differences between compounds in this class, SSRIs possess similar pharmacological activity.

MATERIALS AND METHODS

Materials

Fluoxetine, lactose, starch, aspartame, magnesium trisilicate, talc cross carmellose, crospovidone & sodium starch glycolate

Methods

For the following study, we are Taken captopril. Fluoxetine hydrochloride is the first agent of the class of antidepressants known as selective serotonin-reuptake inhibitors (SSRIs) [5-7]. In this study first, we did preformulation study.

In this preformulation study, we studied about the API characterization of drug, Drug-Excipient compatibility studies, Analytical method development, and Precompression parameters.

API characterization

It is necessary to study the physicochemical properties of the bulk drug-like physical appearance, solubility, melting point, particle size, and incompatibilities [4].

Analytical method development

It is studied for knowing about the purity of the drug. It is carried out by two methods HPLC or U. V. Here we have followed U. V method [9, 10]. Then we went for the formulation development.

Formulation development and evaluation

For this study, we developed 9 formulations in different ratio. The following table is shown formulation development for the present study.

Table 1: Formulation composition of orodispersible tablet of fluoxetine hydrochloride for wet granulation method

Ingredients

FW1

(mg)

FW2

(mg)

FW3

(mg)

FW4

(mg)

FW5

(mg)

FW6

(mg)

FW7

(mg)

FW8

(mg)

FW9

(mg)
Drug(Fluoxetine) 10 10 10 10 10 10 10 10 10
Lactose 59.5 58 56.5 59.5 58 56.5 59.5 58 56.5
Starch 20 20 20 20 20 20 20 20 20
Cross carmellose 1.5 3 4.5 - - - - - -
Crospovidone - - - 1.5 3 4.5 - - -
Sodium starch glycolate - - - - - - 1.5 3 4.5
Poly vinyl pyrolidine 5 5 5 5 5 5 5 5 5
Aspartame 3 3 3 3 3 3 3 3 3
Magnesium stearate 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5
Talc 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5

Table: 2 Formulation composition of orodispersible tablet of fluoxetine hydrochloride for sublimation method

Ingredients FS1 (mg)

FS2

(mg)

FS3

(mg)

FS4

(mg)

FS5

(mg)

FS6

(mg)

FS7

(mg)

FS8

(mg)

FS9

(mg)
Drug(Fluoxetine) 10 10 10 10 10 10 10 10 10
Lactose 54.5 53 51.5 54.5 53 51.5 54.5 53 51.5
Starch 20 20 20 20 20 20 20 20 20
Camphor 5 5 5 5 5 5 5 5 5
Cross carmellose 1.5 3 4.5 - - - - - -
Crospovidone - - - 1.5 3 4.5 - - -
Sodium starch glycolate - - - - - - 1.5 3 4.5
Poly vinyl pyrollidine 5 5 5 5 5 5 5 5 5
Aspartame 3 3 3 3 3 3 3 3 3
Magnesium stearate 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5
Talc 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5

RESULTS AND DISCUSSION

Standard graph of Fluoxetine hydrochloride in 0.1N HCl

Table: 3 Data of the standard calibration curve of fluoxetine hydrochloride, Medium 0.1N HCl; λmax=226 nm

Concentration (µg/ml) Absorbance at 226 nm
0 0
2 0.066
4 0.186
6 0.242
8 0.333
10 0.418
12 0.505
14 0.582
16 0.669
18 0.757
20 0.836

Fig. 1: Standard graph of fluoxetine hydrochloride. Medium 0.1N HCl; λmax=226 nm

Preformulation studies

Fourier transforms infrared spectroscopy (FTIR)

Table 4: Observed frequencies in the FTIR spectra of pure drug (fluoxetine hydrochloride) and physical mixture with their assignments

Frequency observed in IR spectrum (cm-1) Assignments

3440.7

1070.1

Amines stretching vibration (N-H)

(N-C) stretching
2960.3 Alkane (C-H stretching)

3014.5

1518.2

Aromatic (C-H stretching)

(C=C stretching)
1242 Phenoxy stretching vibration (C-O-Aromatic group)
1331 Halide stretching vibration (C-F)

1108

1050

842

699

588

526

 Fingerprint absorption bands

Powder characterization

The powder mixtures of different formulations were evaluated for angle of repose, Hausner ratio, and compressibility index and their values were shown in (table 6, 3).

Evaluation of tablets

The Oro dispersible tablets of different formulations were evaluated for Weight variation, Hardness, Thickness, Friability test, Drug content and their values were shown in (table 6, 4).

Fig. 2: FTIR spectra of fluoxetine hydrochloride. (Pure drug)


Fig. 3: FTIR spectra of physical mixture containing drug and Cross carmellose


Fig. 4: FTIR spectra of physical mixture containing drug and Cross povidone


Fig. 5: FTIR spectra of physical mixture containing drug and Sodium starch glycolate


Fig. 6: FTIR spectra of physical mixture containing drug and starch


Fig. 7: FTIR spectra of physical mixture containing drug and PVP


Fig. 8: FTIR spectra of physical mixture containing drug and lactose


Fig. 9: FTIR spectra of drug formulation


Table 5: Flow properties of the final powder blend

Formula code

Bulk density

(gm/cm3)

 Tapped density(gm/cm3)

Carss index

(%)

 Angle of repose Hausners ratio
FW1 0.341±0.04 0.422±0.04 12.46±1.87 27 °.11΄±0.065 1.14±0.01
FW2 0.357±0.03 0.423±0.06 9.50±1.23 26 °.12΄±0.043 1.10±0.03
FW3 0.365±0.12 0.405±0.06 12.75±1.98 28 °.21΄±0.032 1.14±0.01
FW4 0.333±0.32 0.403±0.02 11.11±0.05 28 °.32΄±0.05 1.12±0.03
FW5 0.371±0.05 0.417±0.05 13.08±0.42 27 °.09΄±0.06 1.15±0.02
FW6 0.370±0.06 0.467±0.09 12.69±0.05 29 °.12΄±0.03 1.15±0.03
FW7 0.364±0.06 0.467±0.16 10.61±0.76 27 °.34΄±0.07 1.14±0.06
FW8 0.369±0.09 0.428±0.14 10.73±0.32 30 °.20΄±0.04 1.11±0.02
FW9 0.375±0.05 0.408±0.31 12.55±0.64 26 °.10΄±0.08 1.12±0.03
FS1 0.378±0.01 0.403±0.87 11.21±0.46 27 °.22΄±0.03 1.14±0.05
FS2 0.339±0.07 0.402±0.54 11.81±0.97 27 °.31΄±0.03 1.17±0.06
FS3 0.357±0.12 0.413±0.07 12.09±0.97 28 °.08΄±0.07 1.13±0.03
FS4 0.378±0.14 0.427±0.34 9.95±0.13 29 °.32΄±0.07 1.12±0.02
FS5 0.369±0.15 0.431±0.24 11.13±0.1 31 °.41΄±0.08 1.08±0.01
FS6 0.381±0.21 0.418±0.65 11.28±1.09 29 °.28΄±0.09 1.12±0.02
FS7 0.384±0.06 0.422±0.06 11.57±1.65 28 °.21΄±0.04 1.21±0.05
FS8 0.344±0.25 0.413±0.07 11.75±0.05 29 °.08΄±0.03 1.32±0.02
FS9 0.362±0.14 0.395±0.03 12.53±0.06 27 °.11΄±0.05 1.14±0.05

Data represents mean±SD (n=3)

Table 6: Physical evaluation parameters of orodispersible tablets

Formula code Weight variation(mg) Hardness (Kg/cm2) Thickness (mm) Friability (%) Drug content (%)
FW1 99.4±0.6 3.1±0.1 2.20±0.01 0.41±0.03 95.9±0.07
FW2 98.9±0.81 3.2±0.12 2.22±0.03 0.57±0.04 98.6±0.06
FW3 100.05±0.85 3.3±0.15 2.23±0.035 0.47±0.02 98.1±0.05
FW4 99.6±0.37 3.1±0.13 2.12±0.03 0.34±0.035 97.6±0.02
FW5 100.3±0.53 3.2±0.14 2.20±0.015 0.42±0.03 97.8±0.07
FW6 99.5±0.97 3.4±0.1 2.11±0.03 0.35±0.015 99.1±0.02
FW7 100.3±0.88 3.2±0.17 2.28±0.035 0.46±0.034 95.4±0.04
FW8 99.7±0.51 3.1±0.1 2.30±0.03 0.57±0.015 96.4±0.05
FW9 98.8±0.88 3.2±0.15 2.29±0.04 0.66±0.026 97.1±0.052
FS1 99.5±1.08 2.5±0.21 2.34±0.052 0.62±0.04 96.4±0.041
FS2 100.4±0.65 2.7±0.16 2.37±0.05 0.59±0.05 98.6±0.039
FS3 100.7±1.07 3.0±0.1 2.49±0.05 0.55±0.03 97.1±0.05
FS4 98.8±1.23 2.8±0.2 2.25±0.036 0.5±0.026 99.1±0.045
FS5 99.2±0.19 2.7±0.21 2.31±0.03 0.54±0.03 98.1±0.061
FS6 98.7±0.89 3.1±0.32 2.24±0.07 0.44±0.032 98.3±0.042
FS7 100.3±1.21 2.7±0.08 2.45±0.06 0.61±0.03 96.9±0.061
FS8 98.01±1.46 2.8±0.16 2.51±0.03 0.65±0.04 97.6±0.04
FS9 100.3±0.78 2.7±0.17 2.49±0.04 0.61±0.031 97.8±0.05

Data represents mean±SD (n=3)

Disintegration time

The Orodispersible tablets of disintegration time were evaluated, and their values were shown in (table.6.5. and in fig. 6.10).

Table 7: Disintegration times of orodispersible tablets

Formula code Disintegration time (sec)
FW1 86±4.35
FW2 76±2.51
FW3 72±1.5
FW4 75±1.4
FW5 43±1.15
FW6 35±3.6
FW7 106±4.09
FW8 97±3.6
FW9 86±3.65
FS1 64±4.5
FS2 45±2.51
FS3 41±2
FS4 25±3.05
FS5 20±1.08
FS6 13±1.5
FS7 86±3.7
FS8 74±4.3
FS9 65±3.6

Data represents mean±SD (n=3)


Fig. 10: Disintegration time profile of orodispersible tablets

Wetting time

Wetting time of dosage form is related to the contact angle. The Orodispersible tablets of disintegration time were evaluated, and their values were shown in (table.6.6. and in fig. 6.11 and 6.12).

Table 8: Wetting time of orodispersible tablets

Formula code Wetting time (sec)
FW1 82±2.3
FW2 71±3.1
FW3 65±2.45
FW4 59±3.54
FW5 38±4.12
FW6 30±1.23
FW7 94±5.2
FW8 89±3.21
FW9 80±1.8
FS1 51±1.32
FS2 40±1.42
FS3 37±1.23
FS4 23±1.54
FS5 16±2.32
FS6 10±1.23
FS7 75±1.24
FS8 65±1.45
FS9 54±2.34

Data represents mean±SD (n=3)

Fig. 11: Wetting time profile of orodispersible tablets
Before wetting After wetting

Fig. 12: Photograph of wetting of oro dispersible tablets

In vitro dissolution studies

Table 9: Cumulative percent drug release of formulation with cross carmellose as super disintegrant. Medium= 0.1N HCl, λmax=226 nm

Time(min) FW1 FW2 FW3
5 51.5±0.87 53.3±0.98 57.1±0.57
10 58.3±0.77 60.3±1.04 64.5±0.98
15 67.2±0.98 71.4±0.82 72.3±0.67
20 73.4±1.07 76.3±1.18 79.3±1.67
30 79.3±0.89 81.3±0.87 85.9±1.34
45 82.3±1.06 84.3±0.73 88.5±0.98
60 85.2±0.75 87.5±0.65 91.5±0.85

Data represents mean±SD (n=3)


Fig. 13: Cumulative % drug release of orodispersible tablets incorporated with cross carmellose Vs Time, Medium= 0.1N HCl, λmax=226 nm


Fig. 14: Cumulative % drug release of orodispersible tablets incorporated with Crospovidone Vs Time, Medium= 0.1N HCl, λmax=226 nm


Table 10: Cumulative percent drug releases of formulations with Crospovidone as super disintegrant. Medium= 0.1N HCl, λmax=226 nm

Time(min) FW4 FW5 FW6
5 58.1±0.87 63.2±0.97 67.5±0.87
10 64.4±0.93 69.7±1.38 72.3±0.53
15 70.5±0.65 74.7±0.67 79.6±1.25
20 74.5±0.98 79.4±1.67 84.5±0.76
30 78.3±1.07 86.8±0.65 92.3±1.38
45 82.1±0.89 92.3±0.98 99.4±0.67
60 87.3±1.46 97.5±0.77 -

Data represents mean±SD (n=3)

Table 11: Cumulative percent drug releases of formulations with sodium starch glycolate as super disintegrant. Medium= 0.1N HCl, λmax=226 nm

Time (min) FW7 FW8 FW9
5 50.8±0.97 52.5±1.53 56.3±1.65
10 57.3±0.87 59.5±0.65 62.8±0.98
15 65.5±1.03 68.3±0.97 71.4±0.47
20 71.6±0.63 75.8±0.76 78.3±1.42
30 77.4±0.99 80.3±1.45 82.6±0.95
45 80.6±1.42 83.1±0.63 85.9±0.86
60 83.4±0.86 86.8±0.99 90.4±1.45

Data represents mean±SD (n=3)

Table 12: Cumulative percent drug releases of formulations with Cross carmellose as super disintegrant, Medium= 0.1N HCl, λmax=226 nm

Time (min) FS1 FS2 FS3
5 60.3±0.43 64.3±0.64 67.5±0.83
10 68.6±0.93 70.9±0.46 71.7±0.93
15 73.6±1.36 76.3±0.82 78.3±0.78
20 78.4±0.75 80.2±0.93 85.9±0.63
30 81.3±0.78 85.6±0.62 91.3±1.26
45 87.5±0.86 92.4±0.87 99.3±0.73
60 94.1±0.93 99.1±1.07 -

Data represents mean±SD (n=3)


Fig. 15: Cumulative % drug release of orodispersible tablets incorporated with sodium starch glycolate Vs Time, Medium= 0.1N HCl, λmax=226 nm

The oro dispersible tablets prepared by sublimation method FS-1 to FS-9 by using super disintegrates were evaluated for in vitro drug release behavior, and the results of the formulations were expressed in (tables 6.10-6.12).

Fig. 16: Cumulative % drug release of orodispersible tablets incorporated with cross-carmellose Vs Time, Medium= 0.1N HCl, λmax=226 nm


Table 13: Cumulative percent drug releases of formulations with Cross povidone as super disintegrant, Medium= 0.1N HCl, λmax=226 nm

Time (min) FS4 FS5 FS6
5 69.8±0.88 72.3±0.72 78.9±0.91
10 75.7±0.93 80.3±0.67 89.3±0.85
15 78.6±0.76 88.7±0.94 99.5±0.95
20 81.3±0.83 95.4±0.76 -
30 88.6±0.67 98.9±1.12 -
45 92.4±1.04 - -
60 99.3±0.95 - -

Data represents mean±SD (n=3)

Table 14: Cumulative percent drug releases of formulations with sodium starch glycolate as super disintegrant, Medium= 0.1N HCl, λmax=226 nm

Time (min) FS7 FS8 FS9
5 59.8±0.96 61.4±1.07 65.3±0.84
10 65.8±0.45 67.3±0.87 70.4±0.73
15 71.9±1.13 74.8±0.97 78.3±0.67
20 77.6±0.99 78.8±0.87 83.2±0.68
30 80.4±0.82 84.9±0.73 90.5±0.56
45 85.3±0.95 90.3±0.75 98.9±0.86
60 92.5±0.86 96.3±0.98 -

Data represents mean±SD (n=3)


Fig. 17: Cumulative % drug release of orodispersible tablets incorporated with Cross povidone Vs Time, Medium= 0.1N HCl, λmax=226 nm


Fig. 18: Cumulative % drug release of orodispersible tablets incorporated with sodium starch glycolate Vs Time, Medium= 0.1N HCl, λmax=226 nm


Fig. 19: Comparison of cumulative % drug release of oro dispersible tablets incorporated with Cross povidone Vs Time, Medium= 0.1N HCl, λmax=226 nm

Model fitting data for drug release

Table 15: Kinetic model fitting data for all the formulations prepared by wet granulation method

Batch Zero order First order
FW1 0.820 0.913
FW 2 0.794 0.913
FW 3 0.823 0.941
FW 4 0.894 0.971
FW 5 0.938 0.984
FW 6 0.958 0.986
FW 7 0.831 0.918
FW 8 0.811 0.917
FW 9 0.838 0.952

Table 16: Kinetic model fitting data for all the formulations prepared by sublimation method

Batch Zero order First order
FS1 0.921 0.976
FS2 0.956 0.997
FS 3 0.951 0.981
FS 4 0.964 0.989
FS5 0.910 0.982
FS6 0.991 0.998
FS7 0.918 0.972
FS 8 0.926 0.974
FS 9 0.961 0.931

CONCLUSION

Oro dispersible tablet of fluoxetine hydrochloride prepared using various concentrations (1.5%, 3% & 4.5%) of super disintegrates like crosscarmellose, crospovidone, sodium starch glycolate by wet granulation method & sublimation method. The preformulation studies by FTIR confirmed no interactions between drug and polymers. The prepared formulations were evaluated for the pre-compression parameters & the values were within prescribed limits and indicated good free flowing properties. The physical parameters were found satisfactory & within the limits. Upon comparison sublimation method was showed good results for disintegration time, wetting time & in vitro drug release studies because sublimation of camphor to increase the porosity of the tablets. The tablets prepared with crospovidone at 4.5% concentration (FS-6) by sublimation method was found to be best formulation as it exhibited satisfactory physical parameters, least disintegration time (13 sec.),wetting time (10 sec.) & highest % drug release (99.5%) in 15 min. The drug release pattern from the optimized formulations was best fitted to first-order kinetics.

AKNOWLDGEMENT

We would like to thank our Director sir and other teaching and nonteaching faculty who help to carry out this research in the institution.

CONFLICT OF INTERESTS

Declare none

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