This study formulated and evaluated controlled release aspirin matrix tablets using different concentrations of ethyl cellulose (EC) as the release-retarding polymer. Four formulations (F1-F4) containing 5%, 10%, 15% and 20% EC respectively were developed by direct compression. All formulations exhibited good physical properties. In vitro drug release studies showed that increasing EC concentration decreased the drug release rate from anomalous (non-Fickian) transport. F2 containing 10% EC provided a release profile of 88.87% over 10 hours, meeting the study's objective of sustained release for arthritis treatment.

1. DESIGN AND EVALUATION OF CONTROLLED RELEASE MATRIX TABLET OF ASPIRIN BY USING
ETHYL CELLULOSE (EC)
Tharani a/p Chellandy*, Jiyauddin Khan, and Kaleemullah Mohammed
Unit of Research, School of Pharmacy, Management & Science University,
40100 Shah Alam, Selangor Darul Ehsan, Malaysia
ABSTRACT
Four formulation of sustained release Aspirin were prepared using different concentration of ethyl cellulose through direct compression. Namely they are F1, F2, F3 and F4 using 5%, 10%, 15% and 20 % EC respectively. The
aim of this research project is to study the effect of different concentration of ethyl cellulose on the release of Aspirin in-vitro. In rheumatoid arthritis (RA), there is a circadian rhythm of pain. Joint stiffness and pain is more prom-
inent in the morning in patients with RA. Sustained release aspirin would be useful in the relief of arthritis by dosing before bed-time and it can also be potentially helpful in reducing the gastrointestinal side effects associated
with aspirin. All the prepared formulations showed good physical characteristics. In this study, all the formulations followed first order release kinetics and the drug was released via anomalous release mechanism. Therefore,
both diffusion and erosion was present in the release of drug from these formulations. The use of 10% of ethyl cellulose onwards is able to sustain the release of aspirin. By increasing the concentration of the polymer, the rate
of drug release from its matrix decreases giving a sustained release of the drug. In this study, we are targeting the release of drug for 10 hours. F1 is unable to sustain the release of Aspirin. More than 80% of drug is released
within the first 4 hours. On the other hand, F3 and F4 show a sustained release beyond ten hours where at the tenth hour only 50.81-64.634% of drug is released from the tablet. F2 shows the best release profile for a ten hour
sustained release Aspirin tablet where it releases 88.87% of the drug at the tenth hour. Therefore, F2 will be most suitable formulation for the relief of arthritis by dosing before bed-time compared to F3 and F4.
INTRODUCTION
This study was done to formulate and study the in-vitro release of Aspirin
sustained release using ethyl cellulose as a polymer. The aim of this experi-
ment is to study the effect of different concentration of ethyl cellulose on
the release of Aspirin in-vitro. The main adverse effect associated with As-
pirin is gastrointestinal disturbance and ulcers. Sustained release Aspirin
formulation allows less frequent administration and could potentially de-
crease the side effect. (Hosseinali Tanandeh et al. 2003)
Sustained release Aspirin may be useful in relief of arthritis by dosing be-
fore bed-time (Sarika Pundir et al. 2013). Rheumatoid arthritis is a chronic
inflammatory autoimmune disorder. In rheumatoid arthritis (RA), there is a
circadian rhythm of pain. Joint stiffness and pain is more prominent in the
morning in patients with RA. An increased pain intensity and sleep disturb-
ance is observed during the night and early morning (Cutolo M et al.
2005). In RA, Aspirin is one of commonly used prescribed NSAID. The com-
mon dose used is 325-650mg four to six times a day (Arthritis Medication,
The Arthritis Society, 2011). Aspirin can be given up to 3g a day in RA pa-
tients. However, the dosing has to be tailored according to their gastroin-
testinal capability. Therefore, sustained release of Aspirin that extends its
release for eight to ten hours has potential to be therapeutically beneficial
in rheumatoid arthritis as a bed time dosing.
Ethyl cellulose (EC) is hydrophobic polymer and is essentially tasteless,
odourless, colourless and physiologically and pharmacologically inert.
Ethyl cellulose were found to be a significant rate controlling polymer
which can produce tablets of desired hardness and friability. Although EC
is considered insoluble, it can take up water. EC swells and retard drug re-
lease when it comes in contact with water.
OBJECTIVES
General Objective
To prepare controlled release Aspirin tablets using Ethyl cellulose
(EC) as a polymer.
Specific Objectives
To study the effect of changing the percentage of Ethyl cellulose
(EC) on the dissolution profile of sustained release Aspirin.
METHODOLOGY
RESULTS
Table 1 Spectophotometric da-
ta for construction of Aspirin
standard curve.
Figure 1 Standard curve of Aspirin
Table 2 Results of physical tests of F1-F4
Figure 2 In vitro drug release profile of Aspirin from tablets containing different
concentrations of Ethyl cellulose (EC). N = 3.
Table 3 The mean T50%, MDT and Statistical analysis data of Aspirin tablets con-
taining different concentrations of Ethyl cellulose (EC). N = 3.
Table 4 Kinetics data of Aspirin tablets containing different concentrations of
Ethyl cellulose (EC). N = 3.
Where, r2
is the regression coefficient and n is release, or slope exponent.
DISCUSSION
 Physical characteristics of formulation 1 to formulation 4 are represented by
table 2. All the formulation prepared showed a good physical characteris-
tics. The weight variation of the formulated tablets fell within the prescribed
limits of ± 5%. The hardness of the tablets was found to be within accepta-
ble limits. The acceptable range of hardness or crushing strength of tablet is
5 to 10 kg force (49.03 – 98.07 N). The friability results of all the formula-
tions were within the limit of F<1% (British Pharmacopoeia, 2008).
 Figure 2 shows the mean percentage of drug release profiles of formulation
1-4. The graph shows that by increasing the concentration of EC, there is a
decrease in drug release rate. The order of drug release was F1 (5% EC) >
F2 (10% EC) > F3 (15% EC) > F4 (20% EC). Studies have concluded that
the polymer concentrations are inversely proportional to the release rate of
drug in all formulations (Jiyauddin Khan et al. 2014).
 In F1, the release rate was not decreased to an acceptable level. More than
80% of the drug has been released as early as 4th
hour of the dissolution.
On the other hand, F3 & F4 EC showed a prolonged sustained profile
where, 80% of the drug is not released at the 10th
hour. F2 seems to fulfill
the acceptable criteria where, the release rate of the drug has been de-
creased and at the same time, more than 80% of the drug has been release
at the 10th
hour.
 The mean T50% and MDT values are shown in Table 3. The mean T50% for
F1, F2, F3 and F4 are 1.78 ± 0.01, 3.41 ± 0.02, 5.60 ± 0.01, 9.01 ± 0.14
hours respectively. From this, it can be said that, when polymer concentra-
tion increases, the release of Aspirin from the matrix decreases. P value
less than 0.05 were considered as significant. Therefore, the formulations
are considered statistically significant.
 In reference to table 4, all four formulations follows first-order kinetics. The
first-order equation describes the release from system where dissolution
rate is dependent on the concentration of the dissolving species (Raslan H
K et al. 2006).
 The release kinetics were further evaluated using Higuchi square root mod-
el equation of diffusion as well as Hixson-Crowell equation of erosion. F1,
F3 and F4, follows Higuchi square root model kinetics whereas F2 follows
Hixson-Crowell kinetics. This indicates that the release of drug from F1, F3
and F4 was through diffusion mechanism while in F2 drug release is
through erosion mechanism.
 The dissolution data of drug release profile was fitted into Korsmeyer-
Peppas equation in order to analyze the diffusion and erosion mechanism
of drug release based on the n values. The n value for F1, F2, F3 and F4
are 0.4879, 0.6926, 0.7419 and 0.7189 respectively. This is suggesting that
all the four formulations are following non-Fickian or Anomalous release
mechanism which means there is a combination of both diffusion and ero-
sion drug release mechanism (Chime Salome A et al. 2013).
CONCLUSION
All the prepared formulations showed good physical characteristics. The for-
mulations prepared met all pharmacotechnical parameters including physical
appearance, weight variation, thickness, hardness, and friability. In this study,
all the formulations follow first order release kinetics and the drug was re-
leased via Anomalous release mechanism. Therefore, both diffusion and ero-
sion was present in the release of drug from these formulations. From the
study conducted, it can be concluded that, use of 10% ethyl cellulose onwards
enable to produce a sustained release of aspirin. By increasing the concentra-
tion of the polymer, the rate of drug release from its matrix decreases giving a
sustained release of the drug. In this study, we are targeting the release of
drug for 10 hours. F1 is unable to sustain the release of Aspirin where more
than 80% of drug is released within the first 4 hours. On the other hand, F3
and F4 show a sustained release beyond ten hours where at the tenth hour
only 50.81-64.634% of drug is released from the tablet. F2 shows the best re-
lease profile for a ten hour sustained release Aspirin tablet where it releases
88.87% of the drug at the tenth hour. Therefore, F2 will be most suitable for-
mulation for the relief of arthritis by dosing before bed-time compared to F3
and F4.
REFERENCES
1. Jiyauddin K., Sung Y.K. 2014. Comparative study on the effect of hydrophilic and hydrophobic poly-
mers on the dissolution rate of a poorly water soluble drug. International Journal of Pharmacy and
Analytical Research. 3:291-300.
2. Scott V., Hua D. 2008. Investigation of Ethylcellulose in the Preparation of Theophylline Extended
Release Inert Matrix Tablets. American Association Of Pharmaceutical Science. 4:449-460.
3. Hosseinali Tabandeh, Seyed Alireza Mortazavi, Tina Bassir Guilani. 2003. Preparation of Sustained-
Release Matrix Tablets of Aspirin with Ethylcellulose, Eudragit RS100 and Eudragit S100 and Study-
ing the Release Profiles and their Sensitivity to Tablet Hardness. Iranian Journal of Pharmaceutical
Research : 201-206.
4. Y. Capan, S. Penel, S. Calyb, S. Takka, and A. A. Hyncal. 1989. Formulation and In vitro - In vivo Evalu-
ations on Sustained Release Acetylsalicylic Acid Tablets. Die Pharmazeutische Industrie. 51, 4 : 443-
448.
5. Neel Kamal Kalita and Jatindra Nath Ganguli. 2014. A Study of Controlled Release of Aspirin by Mes-
oporous SBA-15. Chemical Science Transactions. 3(2), 759-763.
6. Chime Salome A, Onunkwo Godswill C and Onyishi Ikechukwu I. 2013. Kinetics and Mechanisms of
Drug Release from Swellable and Non Swellable Matrices: A Review. Research Journal of Pharma-
ceutical, Biological and Chemical Sciences. Volume 4 Issue 2 : 97-103.
7. Gautam Singhvi, Mahaveer Singh. 2011. Review: In-Vitro Drug Release Characterization Models. In-
ternational Journal of Pharmaceutical Studies and Research. Vol. II, Issue I : 77-84.
8. Debjit Bhowmik, Harish Gopinath, B. Pragati Kumar, S. Duraivel, K. P. Sampath Kumar. 2012. Con-
trolled Release Drug Delivery Systems. The Pharma Innovation Journal, Vol. 1 No. 10.
9. Satinder Kakar, Ramandeep Singh, Alok Semwal. 2014. Drug Release Characteristics of Dosage
Forms: A Review. Journal of Coastal Life Medicine. 2(4): 332-336.
10. Sarika Pundir, Ashutosh Badola and Deepak Sharma. 2013. Sustained Release Matrix Technology
and Recent Advance in Matrix Drug Delivery System: A Review. International Journal of Drug Re-
search and Technology, Vol. 3 (1), 12-20.
11.Satyanarayana V, Pavithra Krishnan. 2015. Chronopharmacology: Tailoring Therapy to Endogenous
Rhythms. Journal of International Medicine and Dentistry, 2 (1): 03-16.
12.Arthritis Medications A Consumer’s Guide. 2011. Canadian Rheumatology Association.
Synonyms : Acetylsalicylic Acid (ASA), Acetylsalicylate, Acetylsalicylsaeure.
pKa : 3.49 (at 25 °C)
Solubility: Slightly soluble in water, freely soluble in ethanol (96 %).
Half-life: 3.1–3.2 hours.
Action :
Salicylate; non-selective cyclo-oxygenase inhibitor.
Anti-pyretic; analgesic; anti-inflammatory.
Use :
Rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus er-
ythematosus, osteoarthritis, and ankylosing spondylitis.
PREPARATION OF ASPIRIN CONTROLLED RELEASE TABLETS
Four formulation of Aspirin controlled release were prepared using
different percentage of Ethyl cellulose using direct compression meth-
od. The percentage of Ethyl cellulose used was 5%, 10%, 15% and
20%.
Weighing
Geometrical Mixing
Direct Compression
Finalproduct: subjecttoevaluation&anal-
ysis
 Evaluationofphysicalappearance,
weightuniformity,thickness,diameter,
hardness&friability
 Dissolutiontestanddrugreleaseanaly-
sis.
Concentration Absorbance
0 0
0.035 0.011
0.061 0.015
0.122 0.028
0.244 0.052
0.488 0.095
0.977 0.184
Absorbance(nm)
Concentration (µg /ml)
Formu-
lation
Physical Parameters
Weight (mg),
n = 10 Diameter
(mm)
n = 10
Thick-
ness
(mm)
n = 10
Hardness
(N)
n = 5
Friabil-
ity (%)
n = 10Average
weight
%CV
F1 449.5 ± 2.80 0.62 10.1 ± 0.00 4.9 ± 0.02 70.5 ± 1.42 0.5
F2 449.3 ± 3.83 0.85 10.1 ± 0.00 5.0 ± 0.02 69.9 ± 1.18 0.6
F3 449.9 ± 4.2 0.90 10.1 ± 0.00 4.8 ± 0.01 69.5 ± 1.03 0.6
F4 450.5 ± 3.17 0.70 10.1 ± 0.00 4.8 ± 0.01 69.3 ± 1.76 0.7
Percentageofdrugrelease
Time (hr)
Formulation T50% (hours) MDT (hours)
F1 (5% EC) 1.78 ± 0.01 1.75 ± 0.00
F2 (10% EC) 3.41 ± 0.02 3.35 ± 0.02
F3 (15% EC) 5.60 ± 0.01 3.44 ± 0.00
F4 (20% EC) 9.01 ± 0.14 3.01 ± 0.02
Statistical
significance
P < 0.05 P < 0.05
Formulation Zero-
order
First-
order
Higuchi Hixson-
Crowell
Korsmeyer-
Peppas
r2
r2
r2
r2
r2
n
F1 (5% EC) 0.7124 0.8481 0.8945 0.8197 0.9037 0.4879
F2 (10% EC) 0.9388 0.9957 0.9876 0.9918 0.9880 0.6926
F3 (15% EC) 0.9375 0.9849 0.9869 0.9725 0.9789 0.7419
F4 (20% EC) 0.8967 0.9395 0.9492 0.9264 0.9692 0.7189
Lubrication
 Aspirin
 MCC
 Lactose
 Ethyl cellulose
 Magnesium stearate
 Talc
TABLETS