Enhancement of  of Atorvastatin  Tablet Dissolution  Using


Iraqi J Pharm Sci, Vol.19(1) 2010                                                                     Atorvastatin Dissolution 

                 

 

82 

 

Enhancement of Atorvastatin Tablet Dissolution Using Acid Medium 
Kahtan j.Hasson*

,1
 

* Department of Pharmaceutical Chemistry ,College of Pharmacy,Al-Mustansyria,University.Baghdad .Iraq .  

 
Abstract 
         In this study some generic commercial products of Atorvastatin tablets were evaluated by 

dissolution test in acid medium by comparing with that of parent drug Lipitor of Pfizer Company. 

Some of solubilizing agents were studied in formulation  of Atorvastatin tablet including;  surface 

active agent  and PEG 6000 .The most effective factor was the  use of PEG6000 in formulation of 

Atorvastatin tablet which improved the dissolution and the results of dissolution profile of formulated 

tablet in this work  was bioequivalent to that of Lipitor .The quantitative analysis of this work was 

performed by using reversed phase liquid chromatography and a proper mixture of  mobile phase 

which give a retention time for Atorvastatin about 6 minutes . 

 خالصة 
عهي حثوب االذوزفاسراذيٍ انًُرجح يٍ قثم عدج يعايم دوائيح قي انوسط انحايضي ساء فحص االَحالنيح في هرا انثحث ذى أج         
وفي  ()حثوب نثيروزسكح فايززوانًُرجح يٍ انشسكح األو وهي شذيٍ اتهيح االَحالل نحثوب االذوزفاسرا ساء دزاسح يقازَح يع قوقد ذى أج

ذعرثس يساعدج نهروتاٌ يثم صوديوو نوزيم سهفيد يواد  تإضافحذجازب  إجساءعهي  , كًا اٌ هرا انثحث قد احروىيضي نحاانوسط ا

خ في دحيث ساعاالذوزفاسراذيٍ صيغح حثوب عهي  وقد كاَد انًادج االخيسج ذاخ ذاثيس فعال 0666ويادج توني اثيم غاليكول َوع 

اٌ االصهي ) نثيروز( ًسرحضسان اني  ءيكافي انًسرحضس انًصُع في هرا انثحث وأصثح اَحالنيح االذوزفاسراذيٍ ذحسيٍ  دزجح

تاسرعًال انطوز انعكسي نهكسوياذوغسافيا انسائهح وتاسرعًال خهيط يُاسة نهطثقح انًرحسكح  أجسيدفي هرا انثحث قد  انرحهيالخ انكًيح

  دقيقح ذقسيثا . 0نيعطي وقد انفصم 

 Introduction  
         Atorvastatin calcium is a synthetic lipid-

lowering agent. It is an inhibitor of 3-hydroxy-

3-methylglutaryl-coenzyme A (HMG-CoA) 

reductase. This enzyme catalyzes the 

conversion of HMG-CoA to mevalonate, an 

early and rate-limiting step in cholesterol 

biosynthesis.The absolute bioavailability of 

atorvastatin is approximately 14%. The low 

systemic availability is attributed to hepatic 

first-pass metabolism or mucosa 

gastrointestinal presystemic clearance 
(1)

. The 

plasma concentrations of Atorvastatin and 

other related compounds which are 

metabolized by cytochrome P450 isoenzyme 

CYP3A4 were increased when these drugs are 

taken with repeated use of grape fruit juice due 

to inhibition of this enzyme which is located in 

the gastro intestinal tract 
(2)

.  Atorvastatin 

calcium is practically insoluble in aquouse 

medium below pH4 
(3)

. This physical property 

of insolubility in water, obviously, will lead to 

low dissolution in stomach medium. The first 

study of best dissolution formula which held 

by Pfizer Co. was carried on gastric medium 

,and the use of alkalizing agent (Calcium 

Carbonate) and the  surfactant ( sodium lauryl 

sulphate ) were recommended in formula of 

Atorvastatin tablet
(4)

.Several studies were 

reported in attempt to enhance the dissolution 

of atorvastatin in its solid dosage forms; 

Complexation of Atorvastatin by 

Cyclodexetrin significantly enhanced its 

dissolution, but it is rather tedious procedure 
(5)

. Atorvastatin calcium was prepared as a 

redispersible dry powder for emulsion which 

was formulated by using dextran as a carrier 

and poloxamer 188 as a surfactant, its 

dissolution showed a 2.33 fold increase 

compared to the pure Atorvastatin calcium 

powder in vitro gastrointestinal medium 
(6)

 In 

this present study, Lipitor tablet( 20 mg) , the 

patent drug formulation  of Atorvastatin 

Calcium tablet is tested for dissolution in acid 

medium and the result was about 92 % 

dissolved Atorvastatin to the labeled amount. 

Different generic  products of Atorvstatin 

tablet (commercial products) are evaluated by 

determination of  their dissolution profiles in 

acidic medium .In addition,some experimental 

formulations of Atorvastatin Calcium were 

made in this work and the using of sodium 

lauryl sulfate in different concentrations and 

PEG 6000 have been evaluated by their 

influences on the rate of dissolutions 

.Determinations of the dissoluted amounts of 

Atorvastatin in acid medium are carried in this 

work by using a reversed phase HPLC method, 

prescribed below. Several previous methods of 

analysis have been used for quantitative 

determination of Atorvastatin in tablet 

including spectrophotometry 
(7)

, and HPLC 

method for separation of Atorvastatin and 

Amlodipine in pharmaceutical formulation 
(8)

. 

 

1Corresponding author E- mail :  Kahtan48@yahoo.com 

Received : 9/11/2009 

Accepted : 1/6/2010 

http://www.rxlist.com/script/main/art.asp?articlekey=2710


Iraqi J Pharm Sci, Vol.19(1) 2010                                                                     Atorvastatin Dissolution 

                 

 

83 

 

Experimental work 
Materials 

         Atorvastatin Calcium crystalline powder 

( supplied by Cadila Healthcare Limited 

Company ,India ), Sodium Lauryl Sulphate ( 

Shouguang pharm. Ind.Co.Ltd,China   ), poly 

Ethylene  glycol 6000 ( Sasol Germany 

GmbH.   ), potassium dihydrogen phosphate 

(Reagent grade).Acetonitrile and Methanol 

(HPLC grade). 

Apparatus 

         Uv.vis.spectrophotometer , specord 40, 

analytikjena.HPLC; knauer, Dual piston pump, 

UV detector and computerized recorder,tablet 

Dissolution tester USP 

Procedure  
         6 tablets of each product were tested, one 

tablet  in each of six vessels of the dissolution 

apparatus of paddle system and 50 RPM ,using 

900ml of 0.1M HCL as a medium .the filtered 

samples were taken at intervals; 

10,15,20,25,30,35,40,45 minutes and subjected 

to HPLC analysis to determine the percent  of 

Atorvastatin Calcium dissolved in medium. 

Method of analysis 

         An HPLC method for the analysis of 

Atorvastatin Calcium was carried by using the 

following chromatographic conditions.  

Column:   ODS, 25 cm x 4.6 mm  

Mobile phase: Acetonitrile: 0.01M potassium 

Dihydrogen phosphate solution (40:60), 

adjusted to pH 4.0.with phosphoric acid. 

Detection: by U.V at 240 nm. Flow rate: 1.0 

ml/minutes.Atorvastatin peak appeared in 6 

minutes and the analysis accomplished in 8 

minutes (Figure 1) 

 Figure 1:  HPLC chromatogram of 

Atorvastatin tablet in which The peak of 

Atorvastatin appeared in 6 minutes and the 

Peaks of the excipients are eluted at the first 

minute Which indicated that there is no 

interference with the Assay of Atorvastatin . 
                                                

The accuracy and precision of this HPLC 

method were proved since the relationship of 

different concentrations of Atorvastatin with 

their peak area ratio have shown a straight line 

with correlation coefficient of value 0.999.  

 

 
 

Figure 2: the standard curve of Atorvastatin 

dilutions with percent recovery peak area 

Using the reversed-phase HPLC method. 

 

Dissolution profile  

          Three commercial products of 

Atorvastatin tablet were tested for dissolution 

in acid medium and compared with that of 

patent product (Lipitor). Most of the generic 

formulas of Atorvastatin tablet showed low 

bioequivalence to Lipitor, (see figure 3 )  

 

Figure 3  :dissolution profiles of some 

commercial products of Atorvastatin  

tablets; where  product A ( Avas-

20,MICRO Lab.India)  was bioequivalent to 

Lipitor tablet ,however the product B 

(Atorvatin ,Alfaris Co.Syria) and product  

C (Atorvast 20,Avanzor,Syria) showed low 

dissolution . 

 

Relation between conc.of std Atorvastatin 

and their  % recovery of peak areas

0

10

20

30

40

50

60

70

80

90

1 2 3 4 5 6 7 8

 mg/100 of std Atorvastatin 

%
 
r
e

c
o

v
e

r
y

 
r
e

l
a

t
e

d
 
t
o

t
h

e
 

p
e

a
k

 
a

r
e

a
s

r= 0.9998

Dissolution Profiles of Atorvastatin tablets of different company 

compared to Lipitor tablet

0

10

20

30

40

50

60

70

80

90

100

10 15 20 30 45

m inutes

%
 o

f
 A

t
o

r
v
a
s
t
a
t
in

 r
e
le

a
s
e
d

Lipitor tab.

Product A

Product B

Product C



Iraqi J Pharm Sci, Vol.19(1) 2010                                                                     Atorvastatin Dissolution 

                 

 

84 

 

In my attempt to achieve  good Atorvastatin 

tablet formulation ,different experiments were 

carried in this work considering the acceptable 

physical properties ;hardness,friability and 

disintegration time in addition to the main 

requirement; the high dissolution .The first 

experimental product is termed as (Product D) 

which contained atorvastatin calcium,calcium 

carbonate ,microcrystalline cellulose 

,lactose,colloidal silicone dioxide 

,PVD,magnesium stearate and talc .The 

dissolution profile of this first formula of 

product D was too low comparing to Lipitor 

tablet ( figure 4 ) 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Figur4: dissolution profile of Product D (the 

first experimental batch in this work) which 

showed very low dissolution. 

 

Therefore, product D formula was subjected to 

improvement and several experiments were 

made to evaluate the addition of solubilzing 

agents 

 

1. Effect of surfactant 
          In addition to the ingredients of 
Atorvastatin tablet mentioned above, different 

concentrations of sodium lauryl sulphate( SLS) 

were added in an attempt to increase the 

dissolution of Atorvastatin . Figure (5) shows 

that there is significant increase in dissolution 

of Atorvastatin tablet but it is lower than 80% 

and  there is no significant differences between 

the added  concentrations of 10,20and 40 mg 

of SLS in enhancement of dissolution . 

 

 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure 5:   effect of SLS  on dissolution of 

Atorvastatin tablet in product D. 

 

2. Effect of poly ethylene glycol (PEG 6000) 
         As it is demonstrated in step 1 the 

minimum effective concentration of SLS was 

10 mg per tablet  ,in addition to this substance 

,PEG6000 ( finely sieved powder)  was 

incorporated in different concentrations( 10 

and 20mg ) with  the active constituent of  

Atorvastatin  tablet formulations and the 

dissolutions profile for each formula was 

tested ( see figure -6- ) . The attempts to 

increase the concentration of PEG6000 more 

than 20mg per tablet were failed because the 

other physical properties of tablet (hardness 

and friability) were affected. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure 6 :  effect of PEG 6000 on dissolution 

of Atorvastatin tablet in product D 

 

     

 
 
 

 
 
 

Effect of SLS in Atorvastatin tablet on its dissolution 

0

10

20

30

40

50

60

1 2 3 4 5 6 7 8

minutes

%
 
o

f
 
d

i
s

s
o

l
v

e
d

 

A
t
o

r
v

a
s

t
a

t
i
n No SLS

5mg/tab.SLS

10mg/tab.SLS

20mg/tab.SLS

40mg/tab.SLSDissolution profile of  product D ( Atorvastatin tablet) first 

experimental batch 

0

10

20

30

40

50

60

70

80

90

100

10 15 20 30 45

minutes

%
 
o

f
 
d

i
s
s
o

l
v
e
d

 
A

t
o

r
v
a
s
t
a
t
i
n

 
i
n

 
a
c
i
d

 

m
e
d

i
u

m

Lipitor tab.

prod.D

Effe ct of diffe re nt conce ntrations of PEG 6000 

on dissolution

0

20

40

60

80

100

5 10 15 20 25 30 35 45

minutes

%
 
o

f
 
d

i
s

s
o

l
u

t
i
o

n

without PEG

10 mg PEG

20 mg PEG



Iraqi J Pharm Sci, Vol.19(1) 2010                                                                     Atorvastatin Dissolution 

                 

 

85 

 

Conclusion 
         This study indicated that the formulation 

of Atorvastatin 20mg tablet with the presence 

of SLS (10 mg) and PEG6000 (20 mg) per 

tablet has enhanced the dissolution of 

Atorvastatin to a value equivalent to that of 

parent product (Lipitor). 

 

 

References 
1. Martindale, drug reference, 2007. 

pharmaceutical, Press, London. 

2. Effects of grape fruit juice on 
pharmacokinetics of atorvastatin and 

ravastatin in Japanese , Ichiro Fukazawa 

,et al , British journal of Clinical 

Pharmacology, v57, 2004, page 448-455. 

3. Clark`s Analysis of Drugs and Poisons, 
3rd Edit., Pharm. Press London 

,Atorvastatin  Monograph . 

4. U.S.patent issued on April 18, 2006. 

5. Solubility and stability enhancement of 
Atorvastatin by Cyclodextrin 

Complexation, by china Reddy et al, 

J.pharm.Sci.and technol.,May 2009, 63; 

217-225.  

6. Preparation, characterization and in vitro 
intestinal absorption of a dry emulsion 

formulation containing atorvastatin 

calcium ,by Yong-Mei Yin,et al, Drug 

Delivery ,Vol.16,jan 2009,page 30-36 . 

7. Simultaneous spectrophotometric 
determination of Atorvastatin and     

Amlodipine besylate in tablet, Khan MR 

and Jain D. Indian J.pharm.Sci.2006; 68; 

546-458. 

8. Stability indicating RP-HPLC estimation 
of atorvastatin and amlodipine besylate in 

pharmaceutical formulations , DA Shahi et 

al ,Indian journal of pharmaceutical 

sciences ,2008,70.page 754-760 .