Satish Nayak, D. C. Goupale*, Atul Dubey and Vipin shukla
Bansal College of pharmacy, Bhopal, India
Keywords: Metronidazole, stability, relative humidity.

Metronidazole is commonly used for the treatment of Helicobacter pylori associated peptic ulcer. Though the Metronidazole is relatively stable with little degradation in aqueous phase but its stability is quite higher in non aqueous phase. The current article discusses about the improvement of stability of metronidazole in non aqueous vehicles which may be useful for the development of liquid formulations containing this drug. The stability study of the drug was carried out at different temperatures and relative humidity according to the ICH guidelines. It was found that the Metronidazole was about 3.7, 4.4, 4.8, 5.3 and 5.9 times more stable in 20%, 40%, 60%, 80% and 100 % v/v propylene glycol solution as compared to aqueous solution at 400C and 75% RH.

Article Information

Identifiers and Pagination:
First Page:295
Last Page:300
Publisher Id:JAppPharm (2011 ). 3. 295-300
Article History:
Received:April 21, 2011
Accepted:June 13, 2011
Collection year:2011
First Published:July 11, 2011

Stability of a drug product refers to the chemical and physical integrity of the dosage unit and the
ability of the drug product to maintain the concentration of its active constituents throughout the
intended shelf life period. Stability testing is the main concern in the development of any
formulation in pharmaceutical industries. Stability of a drug product or dosage form is one of the
major problems associated with the development of liquid formulations like syrup, suspension
and emulsions etc. The main objective of stability testing is to provide evidence on how the
quality of drug substance or drug product varies with time under the influence of a variety of
environmental factors such as temperature, humidity and light and to establish a re-test period for
the drug substance or shelf-life for the drug product and recommended storage conditions.
According to the ICH guidelines of stability testing the world is divided into four climatic zones,
I –IV, but the current stability study of Metronidazole is carried out according to the conditions
of climatic zone I and II [1]. The storage conditions according to ICH guidelines are as follows:
· 250C + 20C / 60% RH + 5% RH or 300C + 20C / 65% RH + 5% RH for long term
stability study.
· 300C + 20C / 65% RH + 5% RH for intermediate stability study.
· 400C + 20C / 75% RH + 5% RH for accelerated stability study.
The current article discusses about the improvement of stability of Metronidazole in non aqueous
vehicles which may be useful for the development of liquid formulations containing this drug
Metronidazole was provided as gift sample from Lupin Laboratories, Mumbai. Propylene
glycol and other chemicals were of analytical grade and were procured from CDH Laboratories,
Mumbai. An UV spectrophotometer (model no. 1700) manufactured by Schimandzu, Japan was
used for the analysis purpose and a Stability Chamber (Elite research, Ambala cantt.) was used
for stability studies. All other facilities were provided by the institute itself
1. Preparation of Solutions
All the solutions of Metronidazole with concentration (900 mg/100 ml) were prepared
using aqueous and non aqueous vehicle. Propylene glycol used as non aqueous solvent to
increases the stability of metronidazole solution [2]. Different concentrations of solvents were
used for this study and the concentration of solvent varied as following types:
Stability studies were performed according to ICH guidelines. The samples were stored in
stability chamber at following conditions for a period of 12 weeks [3, 4].
400C + 20C / 75% RH + 5% RH and 250C + 20C / 60% RH + 5% RH.
The samples were withdrawn every week. These samples were analyzed for drug content by UV
spectrophotometer at 277 nm [5, 6]. The results thus obtained are shown as in table 1 and table 2
Table 1: Asssay of drug when stored at 400C with 75% RH
Stability of a drug product refers to chemical and physical integrity of the active
constituents present in it. The amount of active constituents present in any formulation should
not degrade until they show their therapeutic effects. To maintain these characteristics in any
formulation, drug must be combined with such excipients who could maintain the integrity of the
active constituents throughout its shelf life. In this current study we found that the drug
Metronidazole is 3.7, 4.4, 4.8, 5.3 and 5.9 times more stable in 20%, 40%, 60%, 80% and 100 %
v/v propylene glycol solution as compared to aqueous solution at 400C and 75% RH. From the
graph 1 and 2 it is clear that the content of drug in aqueous solution is decreasing rapidly as
compared with non aqueous solution using propylene glycol.
Graph 1: Assay of drug at 400C with 75% RH; Graph 2: Assay of drug at 250C with 60%
From the current study it is concluded that the stability of Metronidazole decreases with
the aqueous vehicles and increases
with the non aqueous vehicles. Now a day the syrups solutions which are not stable in the
aqueous vehicles can be prepared in non
aqueous (propylene glycol). By the use of this vehicle the stability of the solutions can be
defiantly increased.
The authors thanks to Head, Department of Pharmacy, Bansal College of pharmacy for providing
help in carring out this work. Thanks are also due to Lupin laboratories, Mumbai for providing
the active drug Metronidazole.
1. ICH topic Q1A (R2), (2003) stability testing of new drug substances and product. European
medicine agency.
2. Wang, D. P.; Yeh, M. K. (1993) Degradation kinetics of metronidazole in solution. J Pharm
Sci. 82 (1), 95-8.
3. Ghosh, A.; Nayak, U. K.; Roy, P. (2007) Development, evaluation and method selection
for the preparation of lamivudine microspheres. The international journal of pharmacy.
4. Narasimha, R. D.; Srinath, M. S.; Hindustan, A. A.; Kishore, K. R. B.; Vamsi, K. R. P.;
Krishna, M. C.; Kranthi, G.; Raghavendra,
P. (2011) Formulation and in-vitro evaluation of Glimepiride and Parecoxib combination
mucoadhesive tablets. Der pharmacia letter. 3 (1), 185-192.
5. Nayak, B.S.; Nayak, U. K.; Patro, K. B. (2009) Formulation Design, Preparation and In
vitro Evaluation of Mucoadhesive Microcapsule employing control release Polymers to
enhance gastro retention for Oral delivery of Famotidine. Int J Pharm Sci Tech (2) 1, 22-
6. Shakeel, F.; Baboota, S.; Ahuja, A.; Ali, J.; Shafiq, S. (2008) Accelerated stability testing
of celecoxib nanoemulsion containing Cremophor-EL. African journal of pharmacy and
pharmacology. (2) 8, 179-183.

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Editor in Chief
Prof. Dr. Cornelia M. Keck (Philipps-Universität Marburg)
Marburg, Germany


Welcome to the research group of Prof. Dr. Cornelia M. Keck in Marburg. Cornelia M. Keck is a pharmacist and obtained her PhD in 2006 from the Freie Universität (FU) in Berlin. In 2009 she was appointed as Adjunct Professor for Pharmaceutical and Nutritional Nanotechnology at the University Putra Malaysia (UPM) and in 2011 she obtained her Venia legendi (Habilitation) at the Freie Universität Berlin and was appointed as a Professor for Pharmacology and Pharmaceutics at the University of Applied Sciences Kaiserslautern. Since 2016 she is Professor of Pharmaceutics and Biopharmaceutics at the Philipps-Universität Marburg. Her field of research is the development and characterization of innovative nanocarriers for improved delivery of poorly soluble actives for healthcare and cosmetics. Prof. Keck is executive board member of the German Association of Nanotechnology (Deutscher Verband Nanotechnologie), Vize-chairman of the unit „Dermocosmetics“ at the German Society of Dermopharmacy, active member in many pharmaceutical societies and member of the BfR Committee for Cosmetics at the Federal Institute for Risk Assessment (BfR).

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