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 . 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
· 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
MATERIALS AND METHODS
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 . 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
RESULTS AND DISCUSSIONS
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
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.
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