Effect
of pH on Dissolution Profile of Atenolol Sustained
Release Matrix Tablets
Masheer Ahmed Khan*
School
of Pharmacy, Devi Ahilya Vishwavidyalaya,Takshshila Campus, Khandwa
Road, Indore, 452001, India.
ABSTRACT:
The present study was
performed to illustrate the effect of pH on dissolution profile of atenolol sustained release matrix tablets. Atenolol is β-1 cardio selective
adrenergic receptor blocker, widely used in the treatment of hypertension. The
drug is insoluble in water and has half-life of six to eight hours with oral
bioavailability of 50% due to smaller dose of drug (less than 50 mg). Once
daily Sustained release matrix tablets of Atenolol
reduces the frequency of administration and improves the patient compliance. Atenolol matrices were prepared from combination of
polymers HPMCK4M and HPMCK15M to sustain the release of the drug. Multimedia
dissolution studies were performed to mimic the in-vivo condition by doing
in-vitro test and pH/buffer selection is based on the exposure of drug from
stomach to intestine/colon and to ensure the impact of pH changes on
dissolution and release of drug substance for absorption. The study ensures the
impact of pH changes on dissolution and release of drug substance for
absorption.
KEYWORDS: Atenolol, Dissolution studies, matrix.
INTRODUCTION:
Atenolol is a β-blocker, prescribed
widely in hypertension, angina pectoris, arrhythmias, and myocardial
infarction. It has been reported that atenolol
undergoes extensive hepatic first-pass metabolism following oral administration
and has a short biological half-life. Administration of conventional tablets of
Atenolol has been reported to exhibit fluctuations in
the plasma drug levels, resulting either in manifestation of side effects like
nausea, diarrhea, ischemic colitis, and mesenteric arterial thrombosis or
reduction in drug concentration at the receptor site. To reduce the frequency
of administration and to improve the patient compliance, a once daily sustained
release formulation of Atenolol is desirable1-3.
Multimedia dissolution is to mimic the in-vivo condition by doing
in-vitro test and pH/buffer selection is based on the exposure of drug from
stomach to intestine/colon and to ensure the impact of pH changes on
dissolution and release of drug substance for absorption 4-6.
Sustained
release drug delivery system of Atenolol is designed
to achieve a prolonged therapeutic effect by continuously releasing medication
over an extended period of time by using different grades of Hydroxy Propyl Methyl Cellulose
(HPMC) viz. HPMCK4M and HPMCK15M 7-12.
MATERIALS AND
METHODS:
Atenolol was obtained as a gift sample and tablets were
prepared by direct compression using HPMCK4M and HPMCK15M polymer combinations.
Other excipients used were Magnesium stearate,
Talc, MCC and dibasic calcium phosphate.
The tablet weight was taken 290mg and kept constant. The drug was analyzed by
UV spectrophotometry (UV 1601 Shimadzu, Japan) at
224nm.
Physical
Characterization:
The tablets were subjected to their physical
characterization. Hardness, friability and weight variation and found within
the probable limits, Table [1].
Dissolution Studies:
In order to study the effect of
the dissolution medium pH on the drug release pattern, drug release was studied
in phosphate buffer of pH 2.4, 6.8 and 7.4. The dissolution mediums of
different pH were prepared in following manner
Simulated Gastric
fluid:
2g of NaCl and
3.2 g of pepsin were dissolved in water. Then added 80 ml. of 1 M HCl and diluted to 1000 ml. with water.
Phosphate buffer
pH 6.8:
28.80 g of Na2HPO4 and
11.45 g. of KH2PO4 were dissolved in sufficient water to
produce 1000 ml.
Phosphate buffer
ph 7.4 – Solution I –
119.31 g of Na2HPO4 was dissolved in sufficient water to produce
1000 ml. Solution II – 45.36 g of KH2PO4
was dissolved in sufficient water to produce 1000 ml. Then 85 ml. of solution I
and 15 ml. of solution II were mixed and adjusted the pH.
EXPERIMENTAL:
Three tablets of Atenolol were taken into
three different pH of phosphate buffer (pH2.4, pH 6.8 and pH 7.4).The USP
dissolution apparatus was set at rotation 50 rpm and temperature of the
assembly was set at 370 C. The tablets were placed in above prepared
three different media of different pH. Absorbance was
measured at 224 nm by collecting sample at different time interval as follows
0.5,1,2,3,4,6,8,10 and 12 hrs. Five milliliters aliquots were withdrawn at predefined intervals,
and the volume of the dissolution medium was maintained by adding the same
volume of dissolution medium. The percentage drug release was calculated
at different time intervals at different pH. The
graph was plotted between percent drug release and time for different
dissolution media.
RESULTS AND
DISCUSSION:
Physical properties
of the tablets were found within the probable limits as shown in Table (1). The drug content was estimated from
the absorbance obtained. Three
tablets of were taken into three different pH of phosphate buffer (pH2.4, pH
6.8 and pH 7.4).The USP dissolution apparatus was set at rotation 50 rpm and
temperature of the assembly was set at 370 C. The tablets were
placed in above prepared three different media of different pH.
Absorbance was determined at 224 nm by collecting sample at different time
intervals up to 12hrs. The percentage drug release was calculated at different
time intervals at different pH and shown in Table (2). The graph was plotted between percent drug
release and time for different dissolution media and shown in Fig (1).
Table
(1): Physical characteristics of the tablets
FORMULATION |
|
|
|
|
HPMC K4M mg |
HPMC K15M mg |
Weight mg Mean ± SD |
Hardness Kg Mean ± SD |
Friability (%) |
60 |
30 |
290 ±
1.68 |
5.5O ±
0.14 |
0.50-0.09 |
Table
(2): Result of dissolution studies with different pH
Time
hrs. |
Absorbance
(nm.) |
% Drug release |
|||||
pH 2.4 |
pH 6.8 |
pH 7.4 |
pH 2.4 |
pH 6.8 |
pH 7.4 |
||
1. |
.5 |
0.071 |
0.094 |
0.248 |
9.946 |
9.86 |
29.58 |
2. |
1 |
0.120 |
0.143 |
0.279 |
13.10 |
16.06 |
33.58 |
3. |
2 |
0.133 |
0.152 |
0.344 |
14.76 |
16.99 |
42.13 |
4. |
3 |
0.150 |
0.266 |
0.527 |
16.96 |
31.9 |
65.28 |
5. |
4 |
0.192 |
0.368 |
0.628 |
22.36 |
44.8 |
78.58 |
6. |
6 |
0.194 |
0.402 |
0.639 |
23.53 |
49.60 |
70.10 |
7. |
8 |
0.290 |
0.472 |
0.670 |
31.51 |
58.56 |
84.10 |
8. |
10 |
0.365 |
0.629 |
0.753 |
44.76 |
80.10 |
94.68 |
9. |
12 |
0.468 |
0.676 |
0.774 |
58.26 |
85.20 |
97.78 |
Fig (1). Percent drug release
V/s Time in different pH media.
CONCLUSION:
The release profile of atenolol
from the matrices increased continuously with time, and the amount of drug
release best seen in acidic media (pH=2.4). The cumulative amount of drug
release is higher at pH 7.4 than that of pH 6.8 by 12.58 % and then that of pH
2.4 by 39.52 %. This increase in drug release at higher pH can be attributed to
pH dependent solubility of atenolol. As the pH
increases, the solubility of atenolol increases which
might increase drug release from matrices.
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Received on 15.05.2013
Modified on 25.06.2013
Accepted on 30.06.2013
© A&V Publication all right reserved
Research Journal of Pharmaceutical Dosage Forms and Technology. 5(5):
September-October, 2013, 274-276