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 7.4Solution 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

Sr. No

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.

 

REFERENCES:

1.       Goodman and Gilman’s: The Pharmacological basis of therapeutics. 10th edition . Mc-Graw Hill 2001: 709-710pp.

2.       Ansel, HC, Aallen.LV, Popovich NG, “Pharmaceutical dosage forms and drug delivery system” Lippincott Williams & Wilkins, Philadelphia (USA) 2002; 234-235.

3.       Baisya O, Deb J, and Bhowmik M, Formulation and evaluation of sustained release matrix tablet of atenolol based on natural polymer, Research Journal of Pharmaceutical, Biological and Chemical Sciences (RJPBCS), Vol. 3, Issue-  4 (2012).

4.       Khan M.A., Studies on diltiazem hydrochloride sustained release matrices profiles in multimedia dissolution conditions, Research Journal of Pharmaceutical, Biological and Chemical Sciences (RJPBCS), Vol. 4, Issue  2 (2013).

5.       Khan M.A.  and Mehta RK , Studies on Multimedia dissolution Profile of Zolpidem Tartrate Sustained Release Matrix Tablets, Research Journal of Pharmaceutical, Biological and Chemical Sciences (RJPBCS), Vol. 3, Issue-  2 (2012).

6.       Khan M A, Studies on the effect of pH over dissolution profile of diclofenac sodium sustained release tablets, Journal of Drug Delivery and Therapeutics, 2(5), (2012), 65-66.

7.       Khan M.A., Formulation of sustained release diltiazem hydrochloride matrix tablets through optimization and their evaluation, Research Journal of Pharmaceutical, Biological and Chemical Sciences (RJPBCS), Vol. 4, Issue 2 (2013).

8.       Khan M.A.  and Chaturvedi S.C, Formulation of Sustained Release Zolpidem tartrate Matrix Tablets through Optimization and their Evaluation Asian Journal of Chemistry, Vol. 22,Issue 6(2010),4749-4762.

9.       Khan M A, Formulation of sustained release chlorpheniramine maleate tablets through optimization and their evaluation, Journal of drug delivery and therapeutics, 2(5),45-49,(2012).

10.     Khan MA , and  Chaturvedi SC ,  Swelling and Drug Release Studies from Hydrophilic Matrices Containing Combination of Different Grades of Hydroxyl Propyl Methylcellulose, Asian Journal of Chemistry, Vol. 23,Issue8(2011),3566 – 3568

11.     Khan M A, Studies of swelling effect and drug release in hydrophilic matrices containing different grades of polymers, Research J. of Pharm. Biological and Chemical Sci. (4)1,(2013), 1241-1247.

12.     Khan M A, Maheshwari RK, Studies of relationship between swelling and drug release in the sustained release hydrophilic matrices containing different grades of hydroxyl propyl methylcellulose, Research J. of Pharm. Biological and Chemical Sci., Vol 2 , Issue 4, ,(2011), 970-975.

 

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