In-vitro
evaluation of Captopril tablets present in Yemen markets
Maged Alwan Noman, Mahmood Albooryhi, Abduwaly
Ahmad Sayf, and Hussein Omer Kadi
Department of Pharmaceutics. Faculty of Pharmacy, Sana’a University. Yemen
ABSTRACT:
To investigate the quality of drug content
and in vitro availability of different brands of Captopril tablet collected
from different retail pharmacy in Sana'a (Yemen).
The quality and physicochemical equivalence
of fifteen different brands were assessed. The assessment included the
evaluation of uniformity of weigh, friability, crushing strength,
disintegration and dissolution tests as well as chemical assay according to the
Pharmacopoeia.
All fifteen brands Captopril showed
acceptable uniformity of weight, crushing strength except brand D, friability
except brand C and disintegration time.
All brands passed the dissolution test at 20 min. where brand D with the
lower limit and this may be due to the nature of excipients used or the
formulation process. All brands passed
the test of Captopril contents except brand B and O. where the amount of
Captopril in the two brand are relatively small, which means any demixing or segregation during processing result in
non-uniformity of content.
It was concluded that Captopril tablets marketed
in Sana’a - Yemen are of variance quality. In-vitro study indicated that drug
content and dissolutions profiles, are the most important quality control
parameters, are still concern for solid pharmaceutical..
KEYWORDS: Captopril, Yemen, market, in-vitro study
and dissolution.
INTRODUCTION:
Captopril is a widely used antihypertensive drug that
inhibits angiotensin-converting enzyme (ACE, kinase
II), the enzyme that converts angiotensin I to angiotensin II and may also
reduce the degradation of bradykinin (Longer and
Robinson 1990). It is used in the
management of hypertension, in heart failure, following myocardial infarction,
and in diabetic nephropathy (Parfitt and Martindale
1999) However, many developing countries do not have
an effective means of monitoring the quality of generic drug products in the
market. This results in wide-spread
distribution of substandard and/or counterfeit drug products. It was in view of this fact that the World
Health Organization issued guidelines for global standard and requirements for
the registration, assessment, marketing, authorization and quality control of
generic pharmaceutical products ( WHO 1996).
Generic drug products must satisfy the same standards of
quality, efficacy and safety as those applicable to the innovator
products. Preliminary physicochemical
assessment of the products is very important and in vitro dissolution testing
can be a valuable predictor of the in vivo bio-availability and bioequivalence of
oral solid dosage form ( Itiola and Pilpel 1996).
The safety and efficacy of a pharmaceutical dosage form can be
guaranteed when its quality is reliable (Chowdary
and Krishna 2001).
The efficacy of pharmaceutical dosage forms generally depends on
their formulation properties, and manufacturing methods, hence it is likely
that the quality of dosage form may vary (The Pharmaceutical
Codex, 1994 and Yogananda et al 2009).
The prime objective of the present study was to evaluate
and compare the physicochemical equivalence of fifteen brands of
Captopril tablets that are available in local market of Sana’a (Yemen). Also obtaining baseline data towards the
establishment of bioequivalence of the tablets
MATERIAL AND METHODS:
Fifteen brands of Captopril tablets (A to O) were purchased in
their original packages as supplied by manufacturer. All formulations sampled
had a remaining shelf life of 1.5-2 years at the time of study Physical
measurements. Captopril standard was obtained from Shaphaco.
(Sana’a, Yemen). The used sodium chloride, potassium sulphate,
hydrochloric acid, perchloric acid, sodium hydroxide,
anhydrous glacial acetic acid and chloroform were of analytical grade.
The fifteen Captopril brands were selected on the basis of being
registered by the legal authority in in the countries. These brands are illustrated in Table 1.
EXPERIMENTAL:
Physical measurements:
Twenty tablets selected at random were weighed individually and
their average weight calculated to determine the weight uniformity ( BP, 2007). The percentage deviation of each tablet from the average weight
was determined. Twenty tablets were caused to cascade in a friabilator
(Erweka TA, Germany) rotated at 25 rpm for 4 min. The
weight loss was determined as a percentage of the initial weight (BP,
2007). Crushing strength of each of 10
tablets per brand was determined using the Pharmatest
hardness tester (Switzerland). The force
required to break the tablets into two halves was determined (BP, 2007). The disintegration times of six tablets per
brand were determined in distilled water at 37 ± 0.5 oC using the Apex Tablet
Disintegration Apparatus (Erweka, Germany). Determinations were done in triplicate (BP,
2007).
Dissolution tests on the tablets were carried out using Erweka Dissolution tester (Erweka,
Germany). The Apparatus with an USP
specification dissolution rate test type II (Paddle apparatus) with six section
assembly according to the pharmacopeial procedure
with minor modification (USP, 2000), the a basket rotated at 75 rpm (Shah,
1992) using 900 ml buffer pH 6.8 and maintained at 37 ± 0.5oC.
For drug contents an accurately weighed amount of the captopril
powdered tablets, equivalent to about 50 mg of captopril into a 50 ml
volumetric flask. 15 ml of the mobile phase was added, sonicate
for 15 minutes, complete to volume with the mobile phase and filter through
0.45u membrane filter. The test was
carried using Column Ultra spher ODS (75mm X 4.6mm),
mobile phase (methanol : water containing 0.5ml of phosphoric acid 450 ml
(550ml:450ml), at l = 220 nm.,
1 ml/minute flow rate and injected volume 15ul.
Statistical analysis:
Data for weight uniformity test, friability, crushing strength and
the disintegration, dissolution times and drug contents of the tablets were
analyzed by determining the mean ± standard deviation.
RESULTS AND DISCUSSION:
All fifteen brands Captopril samples used in this study were
within their shelf life at the time of investigation and have been registered
by Supreme Board of Drugs and Medical Appliances Ministry of Public Health
Sana'a Yemen. The results of the
physicochemical properties of the various brands of Captopril are presented in
Table 2. All brands showed acceptable
uniformity of weight as none had percent deviation in weight greater than 5% as
stipulated by the British Pharmacopoeia (BP, 2007). The significance of this test is to ensure
that the tablets in each Lot are within the appropriate size range. The
crushing strength of the tablets is an essential criterion in the determination
of the ability of the tablets to resist chipping, abrasion or breakage under
conditions of storage, transportation and handling before storage. The results showed that the brands examined
had mean crushing strength within the range of 3.97 ± 0.6 - 9.73 ± 0.8 kg
(Shah, 1992) except brand D which exceed the pharmacopeial
limits and reach 23.25 ± 3.8. Generally,
hardness of 4 kg is normally considered to be minimum
for a satisfactory tablet (BP, 2007, Shahm, 1992, USP
2000).
Another tablet property related to crushing strength is
friability, which is designed to evaluate the ability of the tablet to
withstand abrasion during packaging, handling and shipping. For compressed tablets, percentage loss in
weight of less than 1% is usually considered acceptable (Banker
and Rhodes 1979).
The results showed that all brands conformed to the required
standard for friability, while brands C(3.46%), failed
to comply. This failure my resulted from
the use of inadequate or insufficient amount of binding agent during
formulation, inadequate moisture content during compression or insufficient
compression pressure during tableting. The disintegration test measures the time
required for tablets to disintegrate into particles. This is a necessary condition for dissolution
and could be the rate-determining step in the process of drug absorption. The BP 1998 stipulates a disintegration time of
not more 15 min for uncoated tablets. The
results of the disintegration test are presented in Table (2), which showed
that all the brands passed the disintegration test.
Table 1:
Different brands of Captopril available in Yemen markets includes, area of
distributions, country of origin, manufacture and expiry dates and registration
no.
|
Brand |
Area of Distributions |
Country of Origin |
Date of Manufacture |
Expiry date |
*Registration(SBD &M) |
|
A |
Yemen market |
Egypt |
4/2007 |
4/2010 |
Yes |
|
B |
Yemen market |
Korea |
10/8/2007 |
9/8/2010 |
Yes |
|
C |
Yemen market |
Korea |
1/8/2008 |
31/7/2011 |
Yes |
|
D |
Yemen market |
Lebanon |
3/2008 |
3/2011 |
Yes |
|
E |
Yemen market |
Syria |
8/2007 |
8/2010 |
Yes |
|
F |
Yemen market |
China |
/9/2007 |
31/8/2010 |
Yes |
|
G |
Yemen market |
Egypt |
9/2008 |
9/2011 |
Yes |
|
H |
Yemen market |
Jordan |
5/2007 |
5/2010 |
Yes |
|
I |
Yemen market |
Germany |
8/2008 |
8/2010 |
Yes |
|
J |
Yemen market |
Syria |
4/2007 |
4/2010 |
Yes |
|
K |
Yemen market |
Syria |
8/2008 |
8/2011 |
Yes |
|
L |
Yemen market |
Yemen |
5/2007 |
5/2010 |
Yes |
|
M |
Yemen market |
Jordan |
6/2008 |
6/2011 |
Yes |
|
N |
Yemen market |
Greece |
Not clear |
12/2011 |
Yes |
|
O |
Yemen market |
American |
2/2009 |
2/2011 |
Yes |
* Supreme
Board of Drugs and Medical Appliances (SBDandMA)., Sana'a, Yemen
Table 2: Physico-chemical
results of the fifteen brands of captopril tablets*.
|
Brand |
Wt. variation (mg) |
Hardness (kg) |
Friability (%) |
Disintegration (min) |
Dissolution rate % at 30 min |
Drug content (%) |
|
A |
221±0.45 |
6.83±0.86 |
0.392±0.52 |
1.41±0.52 |
92.44±0.31 |
101.52±0.86 |
|
B |
174±0.11 |
3.97±0.63 |
0.132±0.12 |
0.33±0.03 |
88.83±0.52 |
90.49±1.22 |
|
C |
150±0.86 |
6.48±0.65 |
3.462±0.02 |
6.81±
0,21 |
94.01±1.02 |
102.39±0.92 |
|
D |
157±0.66 |
23.25±3.82 |
0.841±0.01 |
4.15±
0.04 |
85.62±2.12 |
101.79±0.52 |
|
E |
103±0.80 |
4.63±0.52 |
0.491±0.01 |
6.12
±0.45 |
93.93±2.21 |
97.70±0.76 |
|
F |
145±0.55 |
8.64±1.37 |
0.133±0.03 |
0.49±0.05 |
93.70±0.94 |
104.74±0.44 |
|
G |
100±0.56 |
9.73±1.82 |
0.194±0.01 |
1.17±0.08 |
97.32±0.85 |
104.18±1.24 |
|
H |
201±0.86 |
4.62±0.98 |
0.244±0.00 |
0.45±0.04 |
101.23±0.98 |
103.70±0.25 |
|
I |
126±0.16 |
5.31±0.52 |
0.790±0.01 |
0.49±0.01 |
95.09±3.01 |
98.72±3.11 |
|
J |
199±0.08 |
4.47±0.76 |
0.251±0.03 |
1.22±0.04 |
98.33±1.18 |
95.34±1.23 |
|
K |
189±0.93 |
7.73±0.99 |
0.243±0.05 |
1.27±0.05 |
91.12±0.31 |
102.24±0.82 |
|
L |
121±0.43 |
6.90±0.79 |
0.252±0.01 |
3.00±0.35 |
94.24±0.85 |
99.23±2.23 |
|
M |
105±0.11 |
8.44±0.48 |
0.133±0.01 |
4.61±0.13 |
97.31±0/54 |
95.70±0.09 |
|
N |
92±0.09 |
4.21±0.59 |
0.001±0.00 |
9.52±0.21 |
96.12±1.18 |
97.02±0.94 |
|
O |
101±0.18 |
5.31±0.55 |
0.252±0.06 |
4.47±0.09 |
87.97±2.10 |
90.77±1.13 |
*(Mean ± SD)
The dissolution test is a measure of the amount of the drug
released into the dissolution medium with time.
The United States Pharmacopoeia stipulates that at 20 min., all tablets
should have released into the dissolution medium an amount not less than 80% of
the labeled amount of Captopril. The results illustrated in table (2), show
.that all the brands passed the dissolution test at 20 min. This may be due to the nature of excipients
used or the formulation process. It has
been shown that the dissolution rate of a pure drug can be altered significantly
when mixed with various adjuncts during the manufacturing process of solid
dosage forms (Abdou, 1989).
Furthermore, the fast disintegrating characteristics of Brand B,
F, H and I are not reflected in the dissolution profile. This could be due to the fact that the
disintegrated particles though small enough to pass through the screen of the
dissolution basket, may have retained the active drug within their hard cores
and hence did not release the drug into the dissolution medium. This implies
that the product may not release a significant amount of the drug on absorption
into the systemic circulation and thus leading to therapeutic failure.
The results of the assays that determine the amount of
captopril present in each formulation as illustrated in table (2) showed that,
all the brands contain between 90.49 % and 104.18% of the labeled amount
specified for captopril. According to the USP captopril content not less than 97.5 % and not
more than 102.5 % (Shah, 1992).
So all brands of captopril tablets tested except brand B and O passed
the test for drug content. Brand B and O
contents were 90.49 and 90.77 % which could be due to poor preparation
techniques during formulation and subsequent manufacturing. Thus demixing or
segregation during processing will result in non-uniformity of content.
CONCLUSION:
To conclude, captopril tablets marketed in Sana’a the capital of
Yemen are of variance quality. The
results of the in-vitro study indicated that drug content and dissolutions
profiles, are the most important quality control parameters, are still concern
for solid pharmaceutical products. So
this study highlights the need for constant market monitoring of new products
to ascertain their equivalency to pharmacopoeial
standards.
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Received on 09.11.2011
Modified on 08.12.2011
Accepted on 25.12.2011
© A&V Publication all right reserved
Research Journal of
Pharmaceutical Dosage Forms and Technology. 4(2): March-April 2012, 124-127