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International Journal of Pharmacology and Pharmaceutical Sciences 2014; Vol: 2, Issue: 2, 9-12
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Vol: http://ijppsjournal.org
2, Issue: 2, 1-9.
International Journal of Pharmacology and
Pharmaceutical Sciences
RESEARCH ARTICLE
ISSN: 2394-613X
Effect of Acid, Base and Heat on Different Brands of Baclofen Available in Bangladesh
Md. Jakaria *, Sozib Chandra Datta, Shakawat Hossain, Md. Abdullah al Masum, Md. Abul Barkat Fahad
Department of Pharmacy, International Islamic University Chittagong (IIUC), Chawkbazer, Chittagong-4203, Bangladesh
* Corresponding Author
Abstract
The objective of this study is to develop the degradation studies of different brands of baclofen available in market. Forced
degradation is a process that involves degradation of drug products and drug substances at conditions more severe than
accelerated conditions and thus generates degradation products that can be studied to determine the stability of the molecule.
Different brands available for baclofen, is an orally administered synthetic anti-spastic agent or muscle relaxant. It reduces
spasticity in many neurological disorders. This drug was subjected to different stress conditions as per International Conference
on Harmonization guidelines (ICH). An ultraviolet UV spectroscopic method was developed for analysis of the drug in the
presence of the degradation products. Distilled water was used as a solvents. The amount of degraded drugs was calculated by
taking the absorbance at 220 nm. According to the assay limit of USP specified that the content should not be less than 95%
and not more than 105% of labelled amount. In acidic pH all brands were degraded and all brands also degraded in basic pH. In
addition to heat exposure no brands were stable that means all brands were degraded. It was concluded that all brands degraded
from ranges for all the stresses applied for degradation studies.
Key Words: Baclofen, anti-spastic, degradation studies, Assay, USP
Introduction
Chemical stability of pharmaceutical molecules is a matter of great concern as it affects the safety and efficacy of the drug product.
The FDA and ICH guidance’s state the requirement of stability testing data to understand how the quality of a drug substance and drug
product changes with time under the influence of various environmental factors Knowledge of the stability of molecule helps in
selecting proper formulation and package as well as providing proper storage conditions and shelf life, which is essential for
regulatory documentation. Forced degradation is a process that involves degradation of drug products and drug substances at
conditions more severe than accelerated conditions and thus generates degradation products that can be studied to determine the
stability of the molecule. The ICH guideline states that stress testing is intended to identify the likely degradation products which
further helps in determination of the intrinsic stability of the molecule and establishing degradation pathways, and to validate the
stability indicating procedures used [1]. Baclofen is chemically β-(amino methyl)-4-chlorobenzene propanoic acid (Fig.1) and it is
used as antispastic agent or muscle relaxant. The molecular formula of Baclofen is C 10 H 12 ClNO 2 , the molecular mass of Baclofen is
213.67g/mol. It is freely soluble in water, 0.1N HCl and 0.1N NaOH, slightly soluble in methanol, very slightly soluble in ethanol [2].
Fig 1. Chemical structure of Baclofen
Jakaria M et.al. Int. J.Pharmacol. Pharm.Sci (2015) 2:2; 9-12
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Baclofen is an orally administered synthetic antispastic agent or muscle relaxant [3]. It reduces spasticity in many neurological
disorders like multiple sclerosis, amyotrophic lateral sclerosis, spinal injuries and flexor spasms but is relatively ineffective in stroke,
cerebral palsy, rheumatic and traumatic muscle spasms and parkinsonism [4]. It may act as an agonist at GABA-B receptors [5]. It is
official drug in I.P, B.P and U.S.P [6-8]. Literature survey reveals that, only bioanalytical methods by HPLC and few
Spectrophotometric methods were found using human plasma and urine for the quantitative estimation of baclofen in bulk drug and
pharmaceutical formulations [2]. The aim of present work is to develop and validate a simple UV spectrophotometric method to be
applied for analysis of baclofen degradation in tablets, which serves as a tool for the quality control of pharmaceutical dosage forms.
Our research group done these type of degradation studies on different brand drugs such as atorvastatin, rabeprazole etc. and these
are very helpful for health care professionals [9-13].
Materials and Methods
Reagents: Analytical grade reagents were used 0.1N sodium hydroxide, 0.1N hydrochloric acid, de-mineralized water and distilled
water.
Glasswares: Volumetric flask, funnel, beakers, Measuring cylinder, pipette, and stirrer used were of Pyrex type and were washed
followed by thorough washing with water and finally rinsed with distilled or de-mineralized water which was freshly prepared in the
laboratory.
Instruments: Theses include

Spectrophometer: UV-vis spectrophotometer, UV mini-1240, Shimadju.

Corvettes

Weighing Balance: Precision balance, LF224DR, Shinko Denshi Co., ltd.

Water Bath: Stainless-steel, thermo station, HH-S
Wavelength Selection: About 100 ppm of baclofen was accurately prepared in distill water. The wavelength maxima (λmax) was
observed at 220 nm and this wavelength was adopted for absorbance measurement.
Preparation of 0.1 N Sodium Hydroxide: 0.4 grams of sodium hydroxide was taken and transferred it in 100ml volumetric flask and
dissolve it in small quantity of water and finally make up the volume up to mark of the flask with de-mineralized water.
Preparation of 0.1 N Hydrochloric Acid: 8.36 ml analytical grade hydrochloric acid (37%, 12N) was taken in a volumetric flask and
de-mineralized water was added to making up to the volume.
Standard Stock Solution: The five different brands were purchased from a local drug shop located in Bayezid Bostami, Chittagong.
All tablets of brand were labeled to contain baclofen 10 mg per tablet. Showing manufacturing and expire date of different brands
(Table 1). Weigh and finally crushed tablets accurately for making primary solutions of baclofen 10 mg, Myorel (0.1236 gm)
Healthcare Pharmaceuticals Ltd., Baclon (0.1869 gm) Orion Pharma Ltd., Flexibac (0.1411 gm) Beacon Pharmaceuticals Ltd., Beklo
(0.1027 gm) Opsonin Pharma Ltd., Bacmax (0.0994) Drug International Ltd. were weighed accurately and introduced in 100 ml
volumetric flasks. Distill water was added and shaken vigorously and was making up the volume up to 100 ml to make the strength of
the solution 100ppm in 100 ml.
Table 1: Showing manufacturing and expire date of different brands
S. No.
Brand name
Mfg. Date
Exp. Date
1.
Myorel
August , 2014
August, 2016
2.
Baclon
11 June, 2014
11 June, 2016
3.
Flexibac
January, 2013
May, 2015
4.
Beklo
June, 2014
June, 2016
5.
Bacmax
October, 2014
October, 2016
Jakaria M et.al. Int. J.Pharmacol. Pharm.Sci (2015) 2:2; 9-12
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Procedure For Acid: To study the effect of acid, take 5 ml of 100 ppm solution of each brand in five separated test tubes then 5ml of
0.1N HCl is added in each test tube. They were then left for a period of 1 hours. Upon completion of time period, solutions were
transferred to acuvette separately and then absorbance of the solutions was recorded at the wavelength of 220 nm.
For Base: To study the effect of acid, 5 ml of 100 ppm solution of each brand was taken in five separated test tubes then 5 ml of 0.1N
NaOH is added in each test tube. The samples were then left for a period of 1 hours. Upon completion of time period, solutions were
transferred to a cuvette separately and then absorbance of the solutions was recorded at the wavelength of 220 nm.
For Heat: To study the effect of heat, 5 ml of 100 ppm solution of each brand was taken in five separated test tubes each containing 5
ml of water, than place these solutions in water bath for 1 hours and absorbance of the solutions was recorded at the wavelength of
220 nm.
Result and Discussion
The purpose of degradation studies is to investigate those changes, to get a shelf life for the drug product and to recommend storage
conditions, which will be applicable to all future batches of the tested drug product manufactured and packaged under similar
circumstances [13]. This research was performed with the purpose to compare the degree of degradation in five different brands of
baclofen 10 mg. Table 2, shows the variation in absorbance after the effect of different degradation parameters. The limit of assay by
USP specified that the content should not be less than 95% and not more than 105% of labeled amount. According to USP specified
limit, in case of acidic pH and basic pH all brands of baclofen were mostly degraded. Showing that pH alteration has the most
degradation impact of these products (Table 3, 4). In addition to heat exposure no brands were stable that means all brands were
degraded (Table 5).
Table 2: Showing absorbance of drug in different parameters
S. No.
Brand name
Absorbance of
standard
1.
2.
3.
4.
5.
Myorel
Baclon
Flexibac
Beklo
Bacmax
2.457
2.457
2.370
2.370
2.265
Absorbance
after acidic pH
effect
2.147
2.222
2.147
2.104
2.011
Absorbance
after basic pH
effect
1.929
1.976
1.784
1.976
1.962
Absorbance
after heat
effect
2.018
2.141
2.072
2.085
1.931
Table 3: Showing effect of acid
S. No.
Brands
% Assay
1.
2.
3.
4.
5.
Myorel
Baclon
Flexibac
Beklo
Bacmax
87.38%
90.43%
90.59%
91.59%
88.78%
S. No.
Brands
% Assay
1.
2.
3.
4.
5.
Myorel
Baclon
Flexibac
Beklo
Bacmax
78.51%
80.42%
75.27%
83.37%
86.62%
Table 4: Showing effect of base
Jakaria M et.al. Int. J.Pharmacol. Pharm.Sci (2015) 2:2; 9-12
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Table 5: Showing effect of heat
S. No.
Brands
% Assay
1.
2.
3.
4.
5.
Myorel
Baclon
Flexibac
Beklo
Bacmax
82.13%
87.13%
87.42%
90.77%
85.25%
Conclusion
Baclofen was found to be degraded in almost all types of stress conditions and was found to be less stable. This degradation study was
the stress degradation studies as per ICH guidelines. The method was used is accurate and precise as well as reproducible and
economical and can be successfully used degradation studies of different dosage form. It was concluded that all brands degraded from
ranges for all the stresses applied for degradation studies.
Acknowledgement
The authors greatly acknowledge to Management and Department of Pharmacy, International Islamic University Chittagong (IIUC),
for supports of valuable instruments and equipments during period of laboratory works.
Conflict of Interest
There is no conflict of interest.
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