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Comparative dissolution studies of marketed preparations and treatment of data

by using ANOVA

Article in International Journal of Advances in Pharmaceutical Sciences · January 2010

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 International Journal of Advances in Pharmaceutical Sciences
1 (2010) 142-146
http://www.arjournals.org/ijoaps.html

ISSN: 0976-1055
Research Article

Comparative Dissolution Studies of Marketed Preparations and

Treatment of Data by Using ANOVA
Vijaykumar Nagabandi1*, M. Santhosh Kumar 1, G. Prasad, K. Someshwar1, A. Varaprasad2

*Corresponding author: Abstract

Vijaykumar Nagabandi Various brands of same dosage forms are available in the market
with the common claim that they are all bioequivalent. The main
1. Vaageswari College of Pharmacy,
Beside LMD Police Station, objective of present study was to conduct the comparative
Karimnagar, (A.P) -505481 dissolution studies of various brands of same dosage form and
2. Balaji College of Pharmacy, treatment of dissolution data obtained by using Analysis of
Choppadandi, Karimnagar, (A.P) Variance (ANOVA) to determine whether all the formulations
Email: [email protected] used were equivalent or significantly different. Six different
brands of paracetamol 500 mg conventional tablets from
different manufacturers were selected in the study and
dissolution testing in 7.8 pH phosphate buffer was conducted for
6 tablets from each brand for 30 min by using electrolab
automated dissolution testing apparatus USP type-II, samples
were withdrawn at every 5 min time interval and analyzed for
drug content by using UV/VIS double beam spectrophotometer.
Percent drug release at each time interval was calculated for total
36 tablets (6X6) and the data obtained was treated with statistical
technique –ANOVA. It was concluded from the study that all the
formulations were equivalent and there was no intra and inter
variation between each and every formulation.
Key Words: Dissolution, Drug release, ANOVA, Phosphate
Buffer

Introduction
lipophilic drugs [2]. Dissolution of the drug substance
Adequate oral bioavailability is a key pre-requisite for is a multi-step process involving heterogeneous
any orally administered drug to be systemically reactions/interactions between the phases of the
effective. Dissolution is defined as the rate of mass solute–solute and solvent–solvent phases and at the
transfer from the surface of the dosage form to the solute–solvent interface3. From the dosage form
bulk of the solution [1]. Dissolution is of primary perspective, dissolution of the active pharmaceutical
importance for all conventional, solid oral dosage ingredient, rather than disintegration of the dosage
forms, and can be the rate limiting step for the form, is often the rate determining step in presenting
absorption of drugs administered orally especially for the drug in solution to the absorbing membrane.

doi:10.5138/ijaps.2010.0976.1055.01016
©arjournals.org, All rights reserved.
 Nagabandi et al. International Journal of Advances in Pharmaceutical Sciences 1 (2010) 142-146

Establishment of an in vitro-in vivo correlation

(IVIVC) could facilitate drug development by Method
reducing the number of in vivo studies required for
confirming both the safety and the efficacy of a drug Preparation of 7.8 PH Phosphate Buffer It is
product or the bioequivalence of products containing prepared according to the Indian pharmacopoeia
the same drug. For drug products intended for Preparation of standard graph 100 mg of pure drug
systemic activity, the biological property produced by (paracetamol) was weighed and dissolved in 10 ml of
the dosage form is usually assumed to be related to methanol and diluted up to 100 ml with distilled water
the presence of the drug in the systemic circulation, in 100 ml volumetric flask. This was first stock
i.e., the pharmacokinetic profile. As the elimination solution and contains 1000mcg/ml of drug. From the
process is generally not affected by the dosage form, first stock 10 ml was taken to another 100 ml
the arrival process of the drug into the general volumetric flask and diluted up to the mark with
circulation is likely to govern the degree to which the distilled water and contains 100 mcg/ml of drug
biological property is produced by the dosage form. concentration. From this second stock various other
On the in vitro side, dissolution of this process is the concentrations were prepared like 4mcg/ml, 6mcg/ml,
most frequently in vitro variables used to generate an 8mcg/ml, 10 mcg/ml and 12mcg/ml. Absorbance
IVIVC [4]. Dissolution efficiency (DE) is defined as values of these concentrations were measured by
the area under the dissolution curve up to a certain UV/VIS double beam spectrophotometer(ELICO
time‘t’, expressed as a percentage of the area under SL164) and standard graph was plotted by taking
the rectangle described by 100% dissolution in the absorbance values on y-axis and concentration values
same time [5]. DE can assume a range of values on x-axis.
depending on the time intervals chosen for
interpretation. This should be preferably greater than Dissolution
t90% value of the formulation. Constant intervals are Dissolution Testing Parameters
chosen for comparison. For example the index DE30
would relate to the dissolution of the drug from a Dissolution Apparatus: Automated Dissolution
particular formulation after 30min and could only be Testing Apparatus Type II (Paddle Type)
compared with the DE30 of other formulation. Dissolution medium: 7.8 pH Phosphate Buffer
Summation of drug release data into a single figure Temperature: 370 C
enables a ready comparison to be made between large RPM: 50
number of formulations. It can be related to in vivo Dissolution Time: 30min
data5. Time interval for each sample: 5 min
Dissolution efficiency values of various Sample withdrawn: 5ml
formulations of different brands can be compared by
applying various statistical techniques like ANOVA, Procedure
and difference observed between the formulations is 900ml of the 7.8 pH Phosphate buffer was placed in
significant or not can also be determined by using the each basket of the dissolution apparatus, assembled
same technique [6]. the apparatus and equilibrated the medium to
37±0.50C. Six tablets of first formulation were placed
Materials and Methods in each basket. Care was taken to ensure that air is
taken out from the surface of the tablet. Five ml of the
Materials
sample was withdrawn for every 5min interval from
Various brands of Paracetamol conventional tablets the zone midway between surface of the dissolution
500 mg like CROCIN, MALIDENS, SYSDOL, P500, medium and the top of the rotating blade, not less
T98, and SIRIPAL were collected from market, than 1cm from the vessel walls and replaced the
potassium dihydrogen phosphate and sodium aliquots withdrawn for analysis with equal volumes of
hydroxide pellets were purchased from SD.Fine fresh dissolution medium. Absorbance of the drug in
Chemicals limited, Mumbai. each sample was measured by using UV-Visible

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 Nagabandi et al. International Journal of Advances in Pharmaceutical Sciences 1 (2010) 142-146

spectrophotometer at λmax 244nm. From the

absorbance values obtained at each time interval
percentage release of the drug was calculated using
standard graph and graph was plotted by taking % of
drug release on y-axis and time on x-axis for each
tablet. Dissolution efficiency was calculated for each
tablet from the graph by using the following formula.
Same experiment was repeated for remaining brands.

Dissolution Efficiency
DE = (0∫t Y.dt) / Y100.t

Analysis of Data by ANOVA7

Fig No. 1 Standard Graph of paracetamol
To the obtained DE values, ANOVA was applied at
95 % confidence interval (0.05% LS)
Total three sum of squares were calculated named
SStotal, SSbetween, and SSwithin according to the formulae
given below
Let a, b, c …..,k be the k groups to be compared
among themselves, n1, n2, n3, …..nk samples in each
group and N, the grand total of all the samples.
Correction Factor = [(∑X) 2/N]
SStotal = ∑ X2 – Correction Factor
SSbetween= [(∑Xa)2/na] + [(∑Xb)2/nb] + [(∑Xc)2/nc] +---
-------+ [(∑Xk)2/nk] – Correction Factor
SSwithin = SStotal - SSbetween

ANOVA Table Fig No. 2. Dissolution graph of Crocin

Source Degrees Sum of Mean F Ratio

of of Square Squares
Variatio Freedo s (SS) (MS)
n m (DF)
Between k-1 SSbetwee SSbetween/( F=
n k-1) MSbetwee
Within N-k SSwithin SSwithin / (N- n/
(error) k)
Total N-1 SStotal MSwithin

Results And Discussion

Standard Graph Standard graph of paracetamol is
shown in figure 1. FigNo.3. Dissolution graph of Malidens

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 Nagabandi et al. International Journal of Advances in Pharmaceutical Sciences 1 (2010) 142-146

Fig No. 6. Dissolution graph of T98

Fig No. 4. Dissolution graph of Sysdol

Fig No. 7. Dissolution graph of Siripal

Fig No. 5. Dissolution graph of P500

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 Nagabandi et al. International Journal of Advances in Pharmaceutical Sciences 1 (2010) 142-146

Dissolution Efficiency found to be equivalent in their dissolution and there

was no intra variation and inter variation between the
Table 1: Dissolution efficiency of all 36 tablets tablets of all the brands.
Tablet Crocin Mali- Sysdol P500 T98 Siripal
No dens References
Tab1 63.33 63.33 50.00 53.33 45.00 50.00 1. Dressman JB, Reppas C. In vitro–in vivo
Tab2 56.67 63.33 46.67 56.67 46.67 53.33 correlations for lipophilic, poorly water
soluble drugs. Eur J harm Sci 2000; 11:73–80.
Tab3 56.67 60.00 53.33 46.67 48.33 50.00 2. Banakar UV. Introduction, Historical
Tab4 60.00 66.67 50.00 50.00 45.00 46.67 Highlights, and the Need for Dissolution
Tab5 56.67 60.00 46.67 56.67 46.67 56.67 Testing. Pharmaceutical Dissolution Testing.
49. New York: Marcel Dekker, 1991:1–18.
Tab6 53.33 73.33 53.33 46.67 48.33 60.00
3. Pillai V, Fassihi R. Unconventional
ANOVA –One way dissolution methodologies. J Pharm Sci 1999;
Factor 88(9):843–851.
4. Amidon GL, Lennerna¨s H, Shah VP, Crison
JRA. Theoreticalbasis for a biopharmaceutics
drug classification: the correlation of in vitro
drug product dissolution and in vivo
bioavailability. Pharm Res 1995; 12:413–420.
5. Umesh V Banakar. Pharmaceutical
Dissolution Testing, New York; Marcel
Dekker.
6. Bolton S. Pharmaceutical Statistics Practical
and Clinical Applications, Second Edition,
Revised and Expanded. New York; Marcel
Dekker.
7. Gurumani.N. Analysis of Variance; An
Introduction to Biostatistics; 221-234

Note: ‘F’ Value from the table, at 0.05 Level of

significance and (DF 5, 35) is 4.50

Conclusion
As the calculated ‘F’ value was lesser than table ‘F’
value, it can be concluded that, all the selected
brands of paracetamol conventional tablets were
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