INTRODUCTION:

As per World Health Organization, the stability of the pharmaceutical dosage form depends on various environmental factors such as temperature, light, humidity and physical or chemical nature of the drug and excipients. The stability of the dosage form ids defined as the ability of the substance or drug product to maintain its defined specificity to retain its identity, strength, quality, purity and elegance throughout the storage period or until its expiry date.¹ Stability of the drug product is determined by conducting accelerated stability studies in which the dosage form is subjected to adverse environmental conditions such as elevated temperature or humidity for a prescribed period. Then the product is evaluated regularly during the test for any physical or chemical changes. The nature of degradation product can be easily assessed the results and from that the shelf life can be calculated. ^2,3

In this study we were conducted the accelerated stability study of a atorvastatin loaded nanoemulsion gel as per ICHQ1A (R2) guidelines for drug products intended to be stored at room temperature.

The accelerated stability studies were carried out at controlled temperature and humidity conditions of 40 ± 2°C and humidity 75 ± 5% RH.

Materials:

Atorvastatin calcium was obtained as gifted sample from Dr. Reddy’s Lab., Hyderabad, India. Tween 80 was purchased from Burgoyn, Mumbai, India. Capmul MCM C8 was obtained as a gift sample from Gattefosse India Pvt. Ltd, Mumbai, India. Sunflower oil from V.V.V & son’s edible oil limited, Virudhunagar, India. Carbopol polymer was obtained from Corel Pharma chem., Ahmedabad, India and Triethanolamine from New India chemical enterprises, Kochi, India. All other chemicals and reagents used were of analytical grade.

methods:

Transdermal nanoemulsion gel of atorvastatin calcium was prepared by dispersing Carbopol 940 in a nanomemulsion formulation (containing sunflower oil as the oil phase at a concentration of 7.18%v/v, Tween 80 as surfactant at a concentration of 35.72%v/v, Capmul MCM as co-surfactant a concentration of 7.14%v/v and water a concentration of 49.96%v/v. Atorvastatin calcium was present in the nanoemulsion at a concentration of 25 mg/mL of sunflower oil) and subsequently neutralizing the Carbopol dispersion using triethanolamine.

According to ICHQ1A (R2) guidelines for drug products intended to be stored at room temperature, the accelerated stability studies were to be carried out at controlled temperature and humidity conditions of 40 ± 2°C and humidity 75 ± 5% RH. Thus for the stability evaluation of the nanoemulsion gel the samples were stored at a temperature of 40 ± 2°C and humidity 75 ± 5% RH. The samples were withdrawn at 0, 30, 60 and 90 days and the physical characteristics and drug content were determined. The zero time samples were used as controls.^4,5

The samples were evaluated for the following parameters:

pH: Samples were withdrawn at regular intervals of time and the pH was determined. The pH of formulated gel was determined by using an auto digital pH meter. 1 gm of gel was dissolved in 100 ml of distilled water and stored for 2 hours. The measurement of pH of formulation was done in triplicate and average values were calculated.⁴

Drug content:

Samples were withdrawn at regular intervals of time and were analyzed for drug content. 1 gm of the prepared gel was mixed with 100 ml of suitable solvent. Aliquots of different concentration were prepared by suitable dilutions after filtering the stock solution and absorbance was measured. Drug content was calculated using the equation, which was obtained by linear regression analysis of calibration curve.⁶

Spreadability:

Samples were withdrawn at regular intervals of time and the spreadability was determined. The spreadability of the formulated gel was measured by placing 0.5 gm of gel within a circle of 1 cm pre-marked on a glass plate, over which a second glass plate was placed. Then a weight of 500 gm was allowed to rest on the upper glass plate for 5 minutes. The increase in diameter due to spreading of gel was observed.⁶

Similarity factor:

The in vitro drug release profile of the samples subjected to accelerated stability studies were compared using similarity factor (f₂). A f₂value of 50-100 indicates that the dissolution profiles are similar. In vitro drug release studies were carried out in 900 mL of phosphate buffer solution (pH 7.4) as the dissolution medium at 32±0.5^oC in a paddle over disc method.

The data for the pH, drug content, and spreadability were analyzed for statistical significance by Student’s t-test with statistical significances set at P < 0.05 using GraphPad Instat Software (GraphPad Software Inc., CA, USA). Shelf life was determined as the time at which the 95% one-sided confidence limit for the mean curve intersects the acceptance criterion of 90% percentage label claim. The data was evaluated using Sigmaplot^TM 12 software (Cranes Software International, Bangalore, India). Percentage label claim (% drug remaining) was plotted against time in months to determine the shelf life.

Results and Discussion:

The stability studies were carried out on the optimized gel formulation (G3). The stability studies were conducted in a stability chamber at 40±2°C and 75±5% R.H. for a period of 3 months. (Table-1)

Table.1: Stability data of nanoemulsion gel after storage at 40±2°C and 75±5% RH

Time (days)	pH	Spread ability (cm)	% Drug remaining	Similarity factor (f₂)
0	6.8 ± 0.01	5.6 ± 0.01	100	-
30	6.79 ± 0.01	5.65 ± 0.01	99.80	88.73
60	6.77 ± 0.01	5.66 ± 0.01	99.24	79.65
90	6.76 ± 0.01	5.67 ± 0.01	98.89	69.27

There was no statistically significant difference (P> 0.05) between the samples after storage as compared to the control (0 h) in terms of pH and Spreadability.

The in vitro drug release profile of the nanoemulsion gel was stored for different time intervals were similar compared to the control (0 h) as indicated by similarity values of above 50.⁵

The in vitro release profiles are shown in Fig. 1.

Percentage label claim (% drug remaining) was plotted against time in months to determine the shelf life (Fig. 2).

Shelf life determination of optimized nanoemulsion gel

The effect of storage conditions (40 ±2°C and 75 ± 5% RH) was studied drug content. From the data a plot was obtained using the software and the shelf life was found to be 19.23 months.

Conclusion:

Accelerated stability studies were carried out according to ICHQ1A (R2) guidelines at controlled temperature and humidity conditions of 40 ± 2°C and humidity 75 ± 5% RH and evaluated for its Ph, spread ability and drug content. Results from stability studies indicated stability of optimized formulation, as there was no significant change in observed physical parameters. The shelf life of nanoemulsion gel was found to be 19.23 months.

ACKNOWLEDGEMENTS:

Pramod K gratefully acknowledges State Board of Medical Research (SBMR), Govt. Medical College, Thiruvananthapuram, India, for providing funding [No. A2-SBMR (2011-2012)/22984/2012/MCT; Dated 28.02.2013] to the study.

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Received on 16.07.2015 Accepted on 06.08.2015

Asian J. Pharm. Tech. 2015; Vol. 5: Issue 3, July- Sept. Pg 188-191

DOI: 10.5958/2231-5713.2015.00027.6