Professional Documents
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pharmaceutical form
rika de Ftima Silva Oliveira1, Roberta de Cssia Pimentel Azevedo1, Rudy Bonfilio1, Diego
Borges de Oliveira1, Gislaine Pereira Ribeiro2, Magali Benjamim de Arajo2*
Laboratory Quality Control Nucleus, Federal University of Alfenas, 2Department of Pharmacy, Federal University of Alfenas
Meloxicam is a broadly used drug in the therapeutics for the osteoarthritis and rheumatoid arthritis
treatments in adults, and it is available in the Brazilian market, as tablet and capsule pharmaceutical
forms. The present work aimed to establish conditions for accomplishment of the dissolution test of 15
mg meloxicam tablets (A and B test products), compared with the reference product, since there is no
monograph about dissolution assays for meloxicam in official summaries. To optimize the conditions
several parameters were tested and, according to obtained results, the use of pH 7.5 phosphate buffer
(900mL, at 37 0.5C) as dissolution medium, paddle method (apparatus 2), stirring speed of the
dissolution medium at 100 rpm and collect time of 60 minutes were considered satisfactory. The samples
were quantified by UV spectrophotometric method at 362 nm. The products presented kinetics of firstorder. Dissolution efficiency values were of 83.25, 83.73 and 88.10% for the A, B and reference products,
respectively. Factors f1 and f2 were calculated and similarity of the tested medicines was demonstrated.
The dissolution test was validated presenting selectivity, linearity, precision and accuracy within of the
acceptance criteria.
Uniterms: Meloxicam/dissolution. Dissolution kinetics. Tablet pharmaceutical forms/dissolution test.
Spectrophotometry.
O meloxicam frmaco amplamente utilizado na teraputica para o tratamento de osteoartrite e artrite
reumatide em adultos, e encontra-se disponvel no mercado brasileiro, sob as formas farmacuticas
comprimido e cpsula. O presente trabalho objetivou estabelecer condies para realizao do teste
de dissoluo de meloxicam 15 mg na forma farmacutica comprimido (medicamentos-teste A e B),
comparado com o medicamento de referncia, visto que no h monografia para o ensaio de dissoluo
com meloxicam em compndios oficiais. Para otimizao das condies, diversos parmetros foram
testados e de acordo com os resultados obtidos, a utilizao de tampo fosfato pH 7,5 (900mL, a
370,5C) como meio de dissoluo, aparato 2 (p), velocidade de agitao do meio de dissoluo
de 100rpm e tempo de coleta em 60 minutos, foram considerados satisfatrios. As amostras foram
quantificadas por espectrofotometria na regio do ultravioleta, a 362 nm. Os produtos apresentaram
cintica de primeira ordem. Para a eficincia de dissoluo encontraram-se valores de 83,25, 83,73 e
88,10% para os medicamentos-teste A e B e referncia, respectivamente. Os fatores f1 e f2 foram calculados,
demonstrando haver similaridade entre os medicamentos avaliados. O ensaio de dissoluo foi validado
apresentando seletividade, linearidade, preciso e exatido dentro dos critrios de aceitao.
Unitermos: Meloxicam/dissoluo. Cintica de dissoluo. Comprimidos/teste de dissoluo.
Espectrofotometria.
INTRODUCTION
Drug absorption from solid pharmaceutical forms
following oral administration depends on the stages of
*Correspondence: M. B. Arajo. Laboratrio Ncleo Controle de Qualidade,
Departamento de Farmcia, Universidade Federal de Alfenas - UNIFAL-MG,
Rua Gabriel Monteiro da Silva, 700 - 37130.000 - Alfenas - MG, Brasil. E- mail:
magali@unifal-mg.edu.br
A r t i cl e
Brazilian Journal of
Pharmaceutical Sciences
vol. 45, n. 1, jan./mar., 2009
68
69
TABLE I - Established conditions for dissolution test optimization of meloxicam reference product in tablet pharmaceutical form
Condition
I
II
III
IV
V
VI
VII
VIII
IX
X
XI
XII
XIII
XIV
XV
Apparatus
Paddle
Paddle
Paddle
Basket
Basket
Paddle
Paddle
Paddle
Basket
Basket
Paddle
Paddle
Paddle
Basket
Basket
To study the drug release kinetics a zero-order kinetic model by plotting the undissolved drug amount versus
the time, and the first-order kinetic model by plotting the
natural logarithm (ln) of the undissolved drug amount
versus the time were used (El Yazigi, 1981; Nikolic et al.,
1992). The kinetic parameters of the dissolution such as
the dissolution rate constant (k) and half-life of release
(t50%) were calculated by using equations of a mathematical model that presented most significant correlation
coefficient.
Dissolution efficiency (ED%) was calculated by
using the ratio between the area above the meloxicam
dissolution curve (ASC) at the time interval between 0
and 60 minutes and the total area of the rectangle (ATR)
(described by 100% dissolution in 60 minutes) (Khan,
1975). The results of ED% values of the tested products
were submitted to variance analysis (ANOVA). Tukey
test was used in order to detect the existence of significant
differences between the averages.
The comparison of the dissolution profiles obtained
from the A, B and reference products was also carried
70
Lower level
Basket
Phosphate buffer
pH = 6.8
50
Upper level
Paddle
Phosphate buffer
pH = 7.5
100
45
60
71
Zero-order (r)
0.8716
0.8478
0.8974
First-order (r)
0.8988
0.9325
0.9722
72
t 50% (min)
7.22
8.06
8.55
k (min-1)
0.096
0.086
0.081
Test
Test
Reference
product A
product B
product
ED (%)
83.25
83.73
88.10
Values represent the mean of six determinations.
The f1 and f2 factors were calculated based on literature data (Brasil, 2004; Moore, Flanner, 1996). The
obtained results showed similarity between dissolution
profiles of the A, B and reference products. Dissolution
profile comparison between test product A and reference
product yield f1 of 8.63 and f2 of 77.54. Dissolution profile
comparison between test product B and reference product
yield f1 of 8.44 and f2 of 81.20. All obtained values are
within the specifications.
CONCLUSIONS
The optimal conditions for accomplishment of the
dissolution test for meloxicam tablets were: 900 mL of pH
7.5 phosphate buffer at 37 0.5 C as dissolution medium,
apparatus 2 (paddle) at the stirring speed of 100 rpm and
collect time in 60 minutes.
The validation showed that the dissolution test is
appropriate for quantification of meloxicam in tablet pharmaceutical form for in vitro studies, presenting selectivity,
linearity, precision and accuracy.
The experimental dissolution profiles of tested products follow first-order kinetics. Based on the dissolution
kinetic parameters (k, t50% and ED%) it was verified that
the analyzed products presented dissolution profiles statistically different regarding the drug release percent of
the pharmaceutical form. Nevertheless, the f1 and f2 results
showed similarity between dissolution profiles of the A, B
and reference products. For definite conclusions about the
bioavailability and bioequivalence of these products, it is
necessary the accomplishment of in vivo studies.
ACKNOWLEDGEMENTS
The authors thank FAPEMIG and PROBIC/
UNIFAL-MG program for financial support conceded to
graduate and scientific initiation students, respectively, and
to the companies that supplied the test products A and B.
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