Iraqi Journal Of Pharmaceutical Sciences


Iraqi J.Pharm.Sci., Vol.17 (1)  ,2008                  Variables affecting pentoxifylline formulation (SR)                

1 

Some Variables Affecting the Formulation of Pentoxifylline (PTX) as  
a  Solid  Sustained  Release  Dosage  Form 

Ahmed H. Hussain**  ,  Yehia I. Khalil*,1   
  * College of Pharmacy, University of Baghdad. , Baghdad , Iraq 
** College of  Pharmacy ,  University of  kofa, Najaf, Iraq 

 
Abstract  
        An inert matrix  that is used to control the release of  (PTX) was prepared using Eudragit RL100 
and RSPM types as matrix forming agent . The matrices were prepared by either dry 
granulation(slugging) , or wet granulation method using chloroform as a solvent evaporation vehichle. 
The cumulative release was adjusted by using polyvinylpyrollidone (PVP) or ethylcellulose (EC) 
polymers .The results indicated that   both methods of preparation were valid for incorporation PTX as 
a sustained release granules .Moreover ,the results revealed that best polymer used  was Eudragit 
RSPM in 3:20 polymer drug ratio .Besides to that ,   the results indicated that the release profiles were 
affected by  pH- medium  , PVP and EC addition as an enhancer or retardant polymer used 
respectively. As well as to the method of preparation . 
Key words :  Pentoxifylline  Sustained Retease ,  Eudragit  RS , RL . 

 
  ةصالخاا

قاقحلاكقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلا.لا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلخنقاق ,100لا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلالاانقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلاجللقويااقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلادتتسماقالتلدل قبلفقسكلاقبلااقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلاع تلحتلىلل قرمقسللقمدختسملا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلاقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلالل الا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلغلاقبلاقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلا.لا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلا
المقسلقسكلللقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلالاانقمدختسملا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلاقمل لققلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلاكعلعا قلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلاتاوقق)لا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلترللا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلل( اقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلاكعلعا قلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلالمعققمدختسملا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلاقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلارللااولااقحدا  قملاا قوتقمل لقق
لا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلاتكلللق .المقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقللاا قلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلا تاتلقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلافقئ قحتقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلادل لتل قحابتاقخااكققح اااقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلايلااقحكعلعا قمدل ققلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلاتكلاقبتا قبلفقشاكقود قلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلا تاتلق

قملالدلق :بلااق .حداقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقللاا قلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلا تاتلقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلافقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقل قلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلحاخاعقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلاكايللقق20:3ئأ ل قلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقل قلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلولوقملالدلقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلختيدوق لق ل الا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلغلاقئا.لا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلخنقاقم تعقق
يستلىققلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلححقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلا ا مااغل فقا اقسدثللقبلفقسكلاقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلايلااق .لا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلياوققلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلافقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلاعلاتقول لوقما لاالما قاقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلتثلوقخللللليحدللا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقل قيتلبققلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلاقيعد قق

بلفقلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلاتللا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلاتق .بتا قبلفقمل لققلا.را عون تيجاردويلا مادختسأب رضح دق نيلفيسكوتنبلا راقع ررحت ىلع ةرطيسلل مدختسملا لاعف ريغلا بلاقلاتكلللق .
 

 Introduction                                                                                            
          Tablet dosage form can be defined as a 
unit dose of medication  containing one or 
more of medicinal agents, with or without 
diluents, made by molding the mixture in a 
suitable compressible shape(1).Sustained 
release dosage form having drug release 
features based on the time or location designed 
to accomplish convenience  and therapeutic 
not offered by conventional release form (2).An 
inert matrix was used to control the drug 
release , and this can   be adjusted by using the 
enhancers such as microcrystalline cellulose , 
polyvinylpyrrolidone or surfactants .Eudragit 
RL100 and RSPM ,are methacrylic 
copolymers introduced as a  coating materials 
with different permeabilities (3) ,  depending   
on functional ionized or neutral groups .They 
are commonly used in sustained release dosage 
forms (4). The  distinguishing letters RL and RS 
related to the initial letters  of  German  words 
" Leihtduchlassig " freely permeable and 
Schwerduchlassig ,  slightly permeable . 

Pentoxifylline (PTX) also called oxpentifylline 
is one of the xanthine vasodilator derivative (5)  
,that improve with its active metabolite  
peripheral aterial circulation, and enhance 
tissue oxygenation  The apparent plasma half 
life of the drug and its metabolite is 2-3 hours . 
On the bases of using PTX as drug of choice in 
chronic  occlusive aterial diseases , therefore ,it 
is of a  wise  candidate drug to be formulated   
in   Sustained release oral dosage form. The 
usual dosage form of PTX in controlled release 
tablet from available maintained one is one 
tablet (400mg.) twice daily . The  objective  of  
this study is  to  prepare controlled release 
PTX matrix tablets , utilizing  dry  and    wet 
granulation technique by using Eudragit RL 
and RS types  with PVP and EC polymers as 
enhancer and retardant materials respectively , 
to control the release of PTX for extended 
period (6) .                                                 

  

  
1 Corresponding author  : E-mail : ybmmaz@yahoo.com 
 Received   :  9/11/2007 
 Accepted   :   5/3/2008 

 
 
 

 
 

  



Iraqi J.Pharm.Sci., Vol.17 (1)  ,2008                  Variables affecting pentoxifylline formulation (SR)                

2 

 Materials and  Methods  
 Materials  
      Pentoxifylline supplied by slovakopharma ,   
Slovenia , Aceton,acetic acid,chloroform 
,ethylcellulose , PVP,from BDH chemicals 
,Ltd.Liverpool , England Disodium hydrogen  
phosphate , HCL ands  Lactose from Reidal 
De Haen Ag Seelz  Hanover , Germany (GER) 
, Eudrait RL100 and RSPM , from  Rhom  
pharma GMBH Weiterstadt GER. ,All other  
reagents were of analytical grade . 
 Equipments  

  Dissolution apparatus ,Copley dissolution   
  DIS 8000 , Copley Scientific , Ltd , UK , 
Hardness tester , Stokes Monsanto   
Corporation Limited ,England ,pH-meter 
,Hanna Instrument pH 211  Microprocessor , 
Italy,Oven , Water bath , Memert UL 80 , 
Rostfrei, Schwach , Germany .  Friabilator , 
Sieves , Roche type Moore and  Wright 
,Sheffield , England ,Sartorious Balance , 
Werk-GmbH ,Type 1265 MD , 2854 
MD,Germany ,Spectrophotometer , Carry win  
UV , Varian ,   Australia ,Tablet Machine 
double punch , Korsch , type  EKO , Erweka 
,GmbH, Kr , Offenbach Main    , Germany   
  

 
 
 
 

 
 Methods : 
 Preparation of Eudragit Solutions : 
       Eudragit solutions RL100 and RSPM were 
prepared separately  at  a  concentrations 5 ,10 
,15% by dissolving the desired amount of 
Eudragit   RL100  and RSPM with the desired 
volume of chloroform , the mixture  was 
shacked for 15 minutes in  25°C until 
homogenous clear    transparent   solution was 
resulted (7)                    
 Wet Granulation :  
        Different formulas ( table 1 ) were 
prepared by weighing the drug and  excipient 
equivalent to 30 tablets after drying , then 
blending the powder and mixed with binding 
solution of Eudragit polymers  used gradually , 
until proper ball test consistency was result 
,The wet mass was screened through 12 mesh 
sieve and dried in pre warmed oven 
maintained at 50°C for 2 hours , the dry 
granules were reduced in size by screening     
them through 16 mesh size sieve . Then an 
equivalent weight of granules that  contain 400 
mg.  PTX was mixed with calculated amount 
of  magnesium  stearate 0.5% w/w for one 
minute and compressed into a tablets  using 
10mm. biconcave double punch compression 
tablets  machine  at   11ton  compression force                                                     

Table (1) . Different Formula  of Pentoxifylline with Different Physical Properties 
of Compressed Tablets 

Frmula PTX (gm) 
Eudragit 
RL(mg) 

Eudragit 
RS(mg.) 

PVP 
(mg) 

EC 
(mg) 

Lactose 
(mg.) 

Magnesium 
stearate 

(mg.) 

Total 
weight 
(mg.) 

Friability 
% 

Hardness 
(mg.) APPEARA 

F1 400 20    127.25 2.75 550 3.0 17.1 Friable , Wdusty 

F2 400 40    107.25 2.75 550 2.8 17.2 Friable , Wdusty 

F3 400 60    87.25 2.75 550 1.5 19 Friable , Wdusty 

F4 400 80    67.25 2.75 550 1.0 >20 Friable , Wdusty 

F5 400  20   127.25 2.75 550 3.0 17.2 Friable , Wdusty 

F6 400  40   107.25 2.75 550 2.7 17.4 Friable , Wdusty 

F7 400  60   87.25 2.75 550 1.5 18.4 Friable , Wdusty 

F8 400  80   67.25 2.75 550 0.9 >20 White Accepte 

F9 400  60 13.8  73.45 2.75 550 0.67 >20 Gray Accepte 

F10 400  60 27.6  59.65 2.75 550 0.54 >20 Faint yellow 
Accepte 

F11 400  60 41.4  45.85 2.75 550 0.32 >20 Faint yellow Accepte 

F12 400  60  13.8 73.45 2.75 550 0.66 20 White Accepte 

F13 400  60  27.6 59.65 2.75 550 0.42 20 White Accepte 

F14 400  60  41.4 45.85 2.75 550 0.34 20 White Accepte 



Iraqi J.Pharm.Sci., Vol.17 (1)  ,2008                  Variables affecting pentoxifylline formulation (SR)                
 

3 

  
Dry Granulation : 
       The  method  of dry  granulation  was  
introduced  as  an  alternative   method for a 
selective formula ( F14 ) , this was briefly 
done by weighing the drug and another 
excipients that equivalent to 30 tablets,then 
blending and compressed by means of wide 
single punch machine into 22mm.                   
diameter slugs. These slugs were reduced in 
their sizes by milling and sieved by 16 mesh 
size sieves , the resulted particles were mixed 
with calculated amount of magnesium stearate 
0.5% (w/w) and compressed  into 10mm. 
double punch  compression tablet machine  at  
the  same compression  force .  
  
Assay of Total  PTX in Prepared  Sustained 
Release ( SR) Tablets: 
         An accurate weight of powder of 
triturated tablets equivalent to 400mg. of PTX 
was   added to 500ml. of distilled water and 
shacked for 15 minutes  and   filter 1ml. of 
filtrate was diluted to the appropriate 
concentrationق(8μg/ml)ققwithقdistilledقwater , 
the absorbance of the final solution was 
determined spectrophotometrically at 274nm 
wave length(5) This    procedure   was  
performed for those tablets prepared in  all 
methods mentioned before .                                                                                                                                                                                                                                                                       
                      
Assay of Total PTX  in Reference SR- Tablets 
(TRENTAL 400mg): 
    Ten tablets of the reference product were 
weighted individually  to get the net weight of 
each tablet , and  then  triturated   together ,  
An accurate weight of triturated powder 
equivalent to 400mg. PTX  was dissolved in 
500ml. distilled water , the final solution was 
diluted   to maintain  PTX concentration at 
8μg/mlقby distilled water   ,   the absorbance 
was measured using UV-spectrophotometer at  
274nm.    wave length  (5) . 
 
Friability and Breaking Strength 
Measurement 
      This measurement was carried out for all 
prepared formulas  using Roche  friabilator . 
the loss in weight of 20 tablets tested before 
and after rotation should not exceed 1% of 
total weight of tablet (8) .On the other  hand   
the hardness of the prepared tablets were 
examined by means of  Monsanto        
hardness tester . 
 
 
 
 
 

 
 

Dissolution Behavior: 
Dissolution of the PTX from prepared tablets 
was carried out using USP basket method 
maintained at 37°C temp. , and 75 r.p.m speed 
for 500ml.of buffer solutions ( pH 1.2 ,4.6,and 
6.8 ). Samples  of 5ml. were withdrawn at  1 
hour time intervals for 6-10 hours then the 
samples filtered and diluted, then cumulative 
drug release was measured at 274nm.   for 
triplicate  samples  .                                                                                                                                                                                                                                                                                                              
  
Results and Discussions  
 Formulation of PTX as  A  SR- Tablets : 
     All the powders blend and granules were 
intended for compression  successfully into 
shiny look appearance  . the breaking strength 
were varied from friable to hard (20kg.) 
hardness. This variation may   be referred to 
the polymer type and concentrations (9 , 10 )  . as 
shown in formula 4 and 8.  On the other hand 
PVP presence gave harder granules  ( formula 
12 )  compared with others ( 11) . The same 
results obtained when ethylcellulose was used 
as retardant  material , since both PVP and EC 
act as binding and consolidating agents in 
tablets formulation (12 ,13) . 
 Dissolution Behavior  
 Effect of Eudragit  Polymer : 
      Figures  (1 and 2) illustrate the 
cumulative release of PTX  from   various  
polymer-drug ratios in phosphate buffer 
(pH6.8) , the results indicated that the drug 
release is increased as a function of increasing 
this ratio for both Eudragit types used , this 
behavior  referred  mainly   to   the thickness       
of the polymer around drug particles, that 
results in a delayed permeation of water inside 
drug particles and dissoluted drug outside 
stagnant layer of PTX particle (14) .On the other 
hand the cumulative        release of PTX from 
two polymers used (fig.3) revealed that after 
10h. of dissolution, the percent of drug release 
from formula 3 is    88% compared with 60% 
in formula 7 ,  while the reference tablet 
(Trental400) gave 51% drug release after same 
period of dissolution . This difference may be 
attributed to the   presence   of  highly   basic  
quaternary ammonium groups (1:20 and 
1:40)ratios for both Eudrait RL and RS types 
,respectively which they undergo more 
solubilization in acidic medium, then the over 
all solubility of the drug within deaggregated 
polymer is increased (15) . 
 
 
 
 
 



Iraqi J.Pharm.Sci., Vol.17 (1)  ,2008                  Variables affecting pentoxifylline formulation (SR)                
 

4 

 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 

Figure 1. The percent of PTX released from 
different formulas at phosphate buffer pH 
6.8 using Eudragit RL100 polymer. 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Figure 2. The percent of PTX released from 
different formulas at phosphate buffer pH 

6.8 using Eudragit RSPM polymer. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Figure 3. The cumulative percent of PTX 
released from formulas 3,7 and Reference 

(Trental 400 mg.) at different pH-medium. 
 
 

 
 Effect of Polymer Type : 
     Concerning the type of Eudragit used  , 
fig.3 demonstrate that the time for 50% drug 
release extended for 2 hours compared with 
more than 5 hours for both Eudragit RS and 
RL , respectively . the   illustration   for   this 
variation related to the higher permeability of 
Eudragit RL than that  of  RS polymer type(16) . 

 
 Effect of PVP   Addition :  
      Based on the results obtained as shown in 
fig .4  ,  It   was   shown   that addition of PVP 
in formula 7 made of Eudragit RS type , 
enhance  the cumulative release to about 96% 
when 7.5% w/w PVP used , compared  with 
50% for reference one this effect may be 
referred to the higher  solubility of PVP in 
different media mainly at pH 5-7 medium (17)  . 

                              
  

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Figure 4. Effect of PVP addition on the 
cumulative released of PTX from tableted 

matrix at different pH-medium. 
 

Effect of EC  Addition :  
       The influence of addition 2.5 ,5 and 7.5% 
w/w of  EC to the matrix  formulation of 
formula 7 was illustrated in  fig. 5 ,which 
represents  the cumulative release of PTX ,It 
was seen that  when EC incorporated as a 
retardant material, a slight less or more in drug 
release was resulted compared with that of 
reference  one (Trental) ,  and in an appreciab 
decrease in drug in drug release compared  
with the other formulas free from EC , which 
is attributed to the insolubility of EC in water, 
besides rigid consolidation of Eudragit RS and 
EC  polymer that retain drug in matrix , this 
phenomena is in a consistent with results 
obtained by Aldermann (18) and Sreubel (19) . 

 
 
 
 

0

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%
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F9
F10
F11
Refrence

---pH1.2--
- 

---pH4.6--- 
-----------pH6.8------------------------------ ------------ 

---pH1.2--- 

---pH4.6--- 

-----------pH6.8------------------------------ ------------ 



Iraqi J.Pharm.Sci., Vol.17 (1)  ,2008                  Variables affecting pentoxifylline formulation (SR)                
 

5 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Figure 5. Effect of Ethylcellulose (EC) 
addition on the cumulative released of PTX 

from tableted matrix at different pH-
medium. 

 
 Effect of Granulation Method :  
       The selected formula  14 was reformulated 
again using dry granulation  method , the 
results indicated that cumulative drug release   
by   this  method gave 75% , compared with 
59% for wet granulation  after 10h. , as shown 
in fig. 6 , this behavior may be referred to the 
solvent  effect  (chloroform vehicle) that used 
in a later method help in a formation of  more 
Van Der Waal"s forces among polymer used 
and PTX (20) . these bonds make a matrix 
more rigid and delayed  drug release through 
them. 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Figure 6. Effect of preparation method on 

the cumulative release of PTX from selected 
formula 14 at different pH medium. 

 

 
 Conclusion : 
- Concerning the method used , the study   
  demonstrate that both methods were valid for   
  formulation of  PTX as promised acceptable    
  SR- granules. But wet method is preferred .                                               
- Both  Eudragits used RL100 and RSPM were  
   succeeded in a formation of  delayed release   
   matrix .      
 - Eudragit RS is best to be used   
    in 3:20 polymer :drug ratio for SR granules   
    to utilize PTX as SR  matrix similar to  
    (Trental400) .                                                                                              
- The dissolution behavior of PTX from  
   prepared granules  varies with different pH- 
   medium , and  coating materials .                                                 
- Generally , the release of PTX is affected by  
   addition of PVP and EC mainly for matrix  
   made of Eudragit  RS(PM) type  in  a  
    concentration  7.5% w/w.                                                                      
 -  Best formula when  EC was added to   
    formula 7   represented  formula  14 . 

 
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0
10
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100

0 2 4 6 8 10
Time (Hour)

%
o

f 
D

ru
g

 R
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ea
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F12
F13
F14
Refrence

---pH1.2--
- 

---pH4.6--- 

-----------pH6.8------------------------------ ------------ 

0
10
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100

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Time(Hour)

%
of

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g 
R

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ea

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Wet Granulation

Dry Granulation

---pH1.2--
- 

---pH4.6--- 

-----------pH6.8------------------------------ ------------ 



Iraqi J.Pharm.Sci., Vol.17 (1)  ,2008                  Variables affecting pentoxifylline formulation (SR)                
 

6 

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