The document summarizes the development of an extended release formulation of bupropion hydrochloride tablets. The objectives were to develop a stable, cost-effective ER formulation and compare it to marketed products. Various ER tablet formulations were prepared using different concentrations of coating polymers and evaluated for drug release. Formulations F9 and F10, which used 8% coating of ethylcellulose 15cps, showed comparable release to the reference product over 16 hours. The developed formulation met the objectives of providing a once-daily ER tablet for bupropion hydrochloride.

1. Formulation and Evaluation of
Bupropion Hydrochloride
Extended Release Tablets
Presented by:
Masudi Harikrishna
Under the guidance of
Mr. C. Suryaprakash Reddy, M. Pharm
Department of Pharmaceutics,
Raghavendra Institute of Pharmaceutical Education and Research (RIPER)
An Autonomous under JNTUA, UGC accorded under 2(f) and 12(B), NBA accredited,
K R Palli Cross, Chiyyedu , Anantapuramu – 5151721, (AP), India.

2. The aim of the present study is to develop a pharmaceutically stable, cost
effective and quality improved formulation of Bupropion hydrochloride extended
release tablets.
The specific objectives are as follows
To study the pre formulation properties of the bupropion hydrochloride
To study the compatibility between the drug and excipients
To optimize the concentration of the ER polymer
To study the pre compression parameters of the blend
To evaluate the post compression parameters of the core and coated tablets
To prepare the stable formulation of the bupropion Hcl ER tablets
To compare the prepared bupropion HCl ER tablets with the marketed samples
AIM & OBJECTIVES OF THE WORK

3. INTRODUCTION:
 Oral controlled drug delivery system:
 Oral controlled release drug delivery is a drug delivery system that provides the continuous
delivery of drugs at predictable and reproducible kinetics for a predetermined period
throughout the course of GI transit and also the system that target the delivery of a drug to a
specific region within the GI tract for either a local or systemic action.
 Pharmaceutical dosage forms that release the drug slower than normal manner at
predetermined rate and necessarily reduce the dosage frequency by two folds are known as
Extended Release Dosage Form. This formulation helps to avoid the side effects
associated with low and high concentrations
 In general the goal of a extended release dosage form is to maintain therapeutic blood or
tissue levels of the drug for an extended period.

4.  In general the goal of a extended release dosage form is to
maintain therapeutic blood or tissue levels of the drug for
an extended period.
The aim of the present study is to develop a
pharmaceutically stable, cost effective and quality
improved formulation of Bupropion hydrochloride
extended release tablets.

5. RATIONALE FOR THE SELECTION OF DRUG
Bupropion Hydrochloride is a new class of anti-depressant ,
For successful treatment of depression it is essential to maintain
the constant plasma drug concentration, it can be achieved by giving
the drug in Extended release dosage form which can improve the
patient compliance. This drug having the dose dependent side effect
due to this there is a need to maintain the constant plasma drug
concentration in the body So, Bupropion Hydrochloride is a suitable
candidate to design extended release dosage .

6. PREFORMULATION STUDIES
API Characterization:
1. Organoleptic properties
2. Flow properties for API
3. Solubility profile
S.No Medium pH
Solubility
(mg/ml)
1 0.1N HCl 1.2 310.36
2
pH 4.5 Acetate
Buffer
4.5
197.58
3
pH 6.8 Phosphate
Buffer
6.8
273.78
4
pH 7.4 Phosphate
Buffer
7.4
364.56
5 Purified water 6.02 272.97

7. 4. FT-IR Spectrophotometry
Here spectral changes in the mixture are the basis for the
determination of compatibility. The obtained spectrums of pure drug
and physical mixture of drug and all excipients were shown below

9. Formulation composition of tablets (F1 to F5)
Bupropion HCl ER tablets(mg) F1 F2 F3 F4 F5
Bupropion HCl 300 300 300 300 300
MCC pH 112 30 30 30 30 30
Povidone k30 22 22 22 22 22
Purified water USP Qs Qs qs Qs Qs
SSF 8 8 8 8 8
Core tablet wt 360 360 360 360 360
ER Coating 20% 15% 10% 12% 12%
EC 10cps 60% 43.2 32.4 21.6 25.92 25.92
TEC 6% 4.32 3.24 2.16 2.59 2.59
HPC 34% 24.48 18.36 8.64 14.69 14.69
Ethanol Qs Qs qs Qs Qs
ER Coated tablet wt 432 414 396 403.2 403.2
DR Coating 5% 5% 5% 5% 5%
Eudragit L30 D55 10.80 10.35 9.90 10.08 10.08
TEC 5% 1.08 1.03 0.99 1.01 1.01
PEG 35% 7.56 7.25 6.93 7.06 7.06
Talc 10% 2.16 2.07 1.98 2.02 2.02
Purified water USP Qs qs qs Qs Qs
Final tablet wt 453.60 434.70 415.80 423.36 423.36

10. Bupropion Hcl ER tablets(mg) F6 F7 F8 F9 F10
Bupropion HCl 300 300 300 300 300
MCC pH 112 30 30 30 30 30
Povidone k30 22 22 22 22 22
Purified water USP Qs qs qs Qs Qs
SSF 8 8 8 8 8
Core tablet wt(mg) 360 360 360 360 360
ER Coating 12% 10% 6% 8% 8%
EC 15cps 60% 25.92 21.6 12.96 17.28 17.28
TEC 6% 2.59 2.16 1.30 1.73 1.73
HPC 34% 14.69 8.64 7.34 9.79 9.79
Ethanol Qs qs qs Qs Qs
ER Coated tablet wt(mg) 403.20 396 381.60 388.80 388.80
DR Coating 5% 5% 5% 5% 5%
Eudragit L30 D55 10.08 9.90 9.54 9.72 9.72
TEC 5% 1.01 0.99 0.95 0.97 0.97
PEG 35% 7.06 6.93 6.68 6.80 6.80
Talc 10% 2.02 1.98 1.91 1.94 1.94
Purified water USP Qs qs qs Qs Qs
Final tablet wt(mg) 423.36 415.80 400.68 408.24 408.24
Formulation composition of tablets (F6 to F10):

11. Preparation of Bupropion hydrochloride tablets
Bupropion
hydrochloride
MCC pellets
Dispensing
Sifting
Wet granulation(Top
spray granulation)
Drying
Lubrication (SSF)
Compression
30 mesh
Povidone Binder solution
Coating

12. Evaluation of pre compression parameters
lubricated blend Bulk density (gm/ml) ±SD* 0.40± 0.0036
lubricated blend Tapped density(gm/ml)
±SD*
0.68 ± 0.0063
Compressibility index(%) ±SD* 16.3 ±0.01
lubricated blend Hausners ratio±SD* 1.19 ±0.006
Evaluation of Post compression parameters
Formulation
Avg wt (mg)
n=20
Assay (%)
n=10
Thickness
(mm)
n=6
Hardness
(KP)
N=6
Friability
(%)
Core tablets 360±0.001 99.6±0.025 4.58±0.021 15.4±0.011 0.4
F1 453.60±0.008 99.4±0.036 5.55±0.041 17.6±0.023 0
F2 434.70±0.005 100.3±0.025 5.47±0.035 16.2±0.027 0
F3 415.80±0.001 100.6±0.023 5.33±0.022 16±0.035 0
F4 423.36±0.004 99.6±0.036 5.40±0.007 15.8±0.016 0
F5 423.36±0.002 99.1±0.025 5.42±0.025 15.6±0.044 0
F6 423.36±0.003 101.3±0.36 5.38±0.011 15.9±0.029 0
F7 415.80±0.008 99.2±0.096 5.32±0.011 15.5±0.001 0
F8 400.68±0.005 99.8±0.096 4.90±0.085 15.4±0.008 0
F9 408.24±0.006 99.99±0.025 5.25±0.081 15.8±0.012 0
F10 408.24±0.007 99.99±0.038 5.28±0.069 15.6±0.04 0

13. IN VITRO DISSOLUTION STUDIES
Dissolution conditions for studying the
drug release from Bupropion
hydrochloride Extended release tablets
Apparatus = USP Type
I (basket)
Agitation speed = 75 rpm
Medium = 0.1N HCl
Volume = 900 ml
Temperature = 37.0 ±
0.50 C
Time intervals = 2,4,8,16
hrs.
Wavelength = 252 nm
0
20
40
60
80
100
120
0 5 10 15 20
F1
F2
F3
f4
%
D
r
u
g
r
e
l
e
a
s
e
Time
(Hrs)
Dissolution Profiles of Formulations
F1 to F10 & Innovator

14. 0
20
40
60
80
100
120
0 2 4 6 8 10 12 14 16 18
%
D
r
u
g
d
i
s
s
o
l
v
e
d
Time (hrs)
F9 Trail
F10 trail
Innovator
Both F9 and F10 showed reproducibility both are compile with the innovator.
Comparison of optimized formulations F9&F10 with innovator
Similarity Factor Calculation
S.No
.
Similarity
factor (f2)
Significance
1. <50 Test and reference profiles are dissimilar.
2. 50 -100 Test and reference profiles are similar.
3. 100 Test and reference profiles are identical.
4. >100 The equation yields a negative value.

15. DISCUSSION:
Drug release from the Extended release tablets were studied by dissolution test apparatus
(Electro lab TDT 08L) at 75 rpm and at 37 ± 0.5°C. 0. LN HCl buffer of pH 1.2 (900ml) was used
as dissolution medium. Samples were withdrawn at different time intervals over a period of 16
hrs. Samples were diluted and assayed at 252 nm for Bupropion Hydro chloride using Agilent UV
Visible double beam spectrophotometer 8453. For comparison of Bupropion Hydro chloride
release from commercial tablet was also studied. Formulations F1 (20%) neither showed
comparable with the innovator nor USP limits.
F2 (15%) contained the lower concentration of coating polymer Ethyl Cellulose 10 Cps has not
shown comparable release. In F3(10%) lower concentration of polymer of grade 10 cps but it
shows the burst release In F4(12%) high concentration of polymer it is comparable with the
innovator and also USP limits. To get reproducibility F5 with the same concentration of polymer
with the same grade for more reproducibility . F4&F5 though they contain same concentration
of polymer ,They were fail in showing the reproducibility of drug release ,So change the polymer
grade from 10 cps to 15 cps
In F6 neither showed comparable with the innovator nor USP limits. In F7 lower concentration
of polymer it has not showed comparable release. In F8 further lowered the concentration of
polymer but it were showed the burst release. In F9 higher concentration of polymer grade
15cps was used ,it showed comparable with the innovator. To get reproducibility we went for
another Trial similar to f9 composition . F10 with the same concentration of polymer shows
comparable with innovator, F9, & USP specifications required for the sustained release
formulations. The similarity factor were calculated and the value for the test product was found
to be 84.30. It is greater than 50 Hence the test formulation was found similar with the innovator.

16. CONCLUSION:
Different Extended release formulations of Bupropion
Hydrochloride were prepared by coating with varying
concentrations of Ethyl cellulose 10cps ranging from 12% to 20 %
& 6% to 12 % with ethyl cellulose 15 cps. The formulation
comprising of 8% of Ethyl cellulose 15 cps ,was able to extend the
release of bupropion Hydrochloride for 16 hrs and also showed
comparable release profile with that of Reference product . The 8%
coating of gum Ethyl cellulose 15 cps was the suitable
concentration to prepare Extended release tablets. Hence 8% ethyl
cellulose, 15 cps polymer were suitable rate controlling polymer for
the preparation of once daily bupropion Hydrochloride extended
release tablets.

17. References:
 1.Lippincott Williams & Wilkins.The Science and Practice of pharmacy,
21 ed. Maryland: The universily of The sciences in philedelphai; 2000.
 2. Brahmankar D.M. and Jaiswal S.B. Biopharmaceutics and
Pharmacokinetics, 1 ed. delhi: Vallabhprakashan; 1995.
 . Tzong-Shi Wanga, I-Shin Shiaha,b,*, Chin-Bin Yeha,b, Chuan-Chia
Chang. Progress in Neuro-Psychopharmacology & Biological
Psychiatry. American journal of emergency medicine 2005; 29(6): 149-
151.
 Tzong-Shi Wanga, I-Shin Shiaha,b,*, Chin-Bin Yeha,b, Chuan-Chia
Chang. Progress in Neuro-Psychopharmacology & Biological
Psychiatry. American journal of emergency medicine 2005; 29(6): 149-
151

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