PHARMANEST

ISSN 0976 - 3090 (Print) 2231 - 0541 (Online)

FORMULATION AND INVITRO EVALUATION OF ENTERIC COATED

TABLETS OF DIDANOSINE
*Vivek Kumar Undralla, 1Haranadh Reddy S, 1Sreerama Krishna T, 2A Seetha Devi, 2P Teja and 3KPR Chowdary
*,1

Donbosco college of Pharmacy, Guntur, Andhra Pradesh, India.

2
Hindu College of Pharmacy, Guntur, Andhra Pradesh,
Vishwabharathi College of Pharmaceutical sciences, Guntur, Andhra Pradesh,

ABSTRACT
The project was undertaken with an aim to formulate, and evaluate Didanosine Enteric coated tablets using different
polymers as release retarding agent . and overcome the gastric juice incompatability, Preformualtion study was done
initially and results directed for the further course of formulation . Based on preformualtion studies different formulation
batches of Didanosine was prepared using selected excipient . Granules were evaluated for tests loss on drying ,
bulk density , tapped density , compressibility index, Hausner ratio . Tablets were tested for weight variation ,
thickness , hardness , friability and in vitro drug release as per official procedure . Change in dissolution parameter
study made it suitable for minute physiological variables. Formulation of sustained release tablet of Didanosine
containing 20 % of Ethyl cellulose Std 100p, diluents MCC and with binder Povidone i.e formulation batch F6 can be
taken as an ideal or optimized formulation of Enteric coated sustained release tablets for 12 hour release as it full fills
all the requirements for sustained release tablet.

INTRODUCTION
From time immemorial, drugs have been an inseparable
part of mankinds history since they fulfill one of our most
basic necessities. To administer these drugs in an
appealing and palatable form and in the required amount
and rate, they have to be developed into an acceptable
dosage form. Thus, the concept of formulation
development was evolved, resulting in solid, liquid and
semi-solid dosage form.
Solid dosage forms
Solid dosage forms are widely prevalent due to their ageold application. Especially, oral solid formulations hold a
high potential as they serve to be most convenient for the
administration of drugs. These have been developed into
a wide range of formulations from conventional dosage
forms for immediate release of the drug to controlled
release dosage forms(1) for the constant rate of drug
release. Oral route is the most convenient and commonly
used method of drug delivery. The most commonly used
pharmaceutical solid dosage forms today include
granules, pellets, tablets and capsules Conventional
medication systems that require multi-dose therapy are
not with out problems. With a view to overcoming these
problems, the current trend in pharmaceutical research
is to design and develop new formulations, thereby
enhancing the therapeutic efficacy of existing drugs
Controlled release (2) (CR) / Sustained release (SR)
technology has rapidly emerged over the past three
decades as a new interdisciplinary science that offers
novel approaches to the delivery of bioactive agents into
the systemic circulation for a prolonged period at a

predetermined rate. The choice of drug to be delivered,

clinical needs, and drug pharmacokinetics are some of
the important considerations in the development of CR /
SR formulations, in addition to the relationship between
the rates of drug release from the delivery system to the
maximum achievable rate of drug absorption in to the
systemic circulation.
The therapeutic advantages of
CR / SR systems over the conventional dosage forms
have been amply documented in the literature. One of
the important advantages is the reduced dosing frequency,
thereby improving patient compliance and therapeutic
efficacy. In order to be divisible, a CR / SR dosage form
must not loose its release characteristics upon division to
avoid dose dumping.(3)
Although a variety of dosage forms have been
developed for the preparation of oral CR / SR
formulations, they broadly fall in to two categories: single
unit dosage forms and multiple (multiparticulate) dosage
forms.

Modified release delivery systems may be divided

conveniently in to four categories.
A) Delayed release
system)

(4)

(Enteric coated drug delivery

B) Sustained release(5)
i) Controlled release
ii) Extended release
C) Site specific targeting
D) Receptor targeting

PHARMANEST - An International Journal of Advances In Pharmaceutical Sciences

Vol. 2 (1) January - February 2011 www.pharmanest.net

40

PHARMANEST

ISSN 0976 - 3090 (Print) 2231 - 0541 (Online)

DELAYED -ACTION AND ENTERIC COATED TABLETS
The delayed-action tablet dosage form is intended to
release a drug after some time delay, or after the tablet
has passed through one part of the GI tract into another.
The enteric coated tablet is the most common example
of a delayed-action tablet product. All enteric coated(6)
tablets (which remain intact in the stomach but quickly
release in the upper intestine) are a type of delayed-action
tablet. Not all delayed action tablets are enteric or are
intended to produce the enteric effect.
The compendia specifications for an enteric coated tablet
are that all of the six tablets placed in separate tubes of
the UPS disintegration apparatus (using discs) remain
intact after 30 min of exposure in simulated gastric fluid
at 37C 2C and then disintegrate within the time
specified for that products monograph. If one or two
tablets fail to disintegrate completely in the intestinal fluid,
the test is repeated on 12 additional tablets; not less than
16 of the total 18 tablets tested must disintegrate
completely. Prior to gastric exposure, the tablets are
immersed in water at room temperature for 5 minutes.
The coatings that are used today to produce enteric effects
are primarily mixed acid functionality and acid ester
functionality synthetic or modified natural polymers.
Cellulose acetate phthalate has the longest history of use
as an enteric coating. More recently, polyvinyl acetate
phthalate(7) and hydroxypropyl methylcellulose phthalate
have come into use. All three polymers have the common
feature of containing the dicarboxylic acid, phthallic acid,
in partially esterified form. These polymers, being acid
esters, are insoluble in gastric media that have a pH of
up to about 4; they are intended to hydrate and begin
dissolving as the tablets leave the stomach, enter the
duodenum (pH of 4 to 6),and move further along the small
intestine, where the pH increases to a range of 7 to 8.
The primary mechanism by which these polymers lose
their film integrity, thereby admitting intestinal fluid and
releasing drug, is ionization of the residual carboxyl groups
on the chain and subsequent hydration. The presence of
esterase in the intestinal fluid that break down ester
linkages of the polymer chains may also play some role,
as may surface activity effects of bile salts and other
components in bile that enter the upper small intestine
via the bile duct.

Enteric coatings (8) are employed for a number of

therapeutic, safety, and medical reasons. Some drugs
are irritating when directly exposed to the gastric mucosa,
including aspirin and strong electrolytes such as NH4Cl.
While for most people the occasional aspirin tablet may
not cause irritation, those on daily doses of aspirin, such
as arthritics, may find gastric upset a major problem.
Enteric coating is one method of reducing or elimination
irritation from such drugs. There are other drugs that if
released in the stomach may produce nausea and
vomiting. The low pH of the stomach destroys others drugs
(for example, erythromycin), and hence enteric coating
may be necessary to bring the drug through that
environment to the more neutral intestinal contents. Yet
another reason for enteric coating may be the desire to
release the drug undiluted and in the highest concentration
possible within the intestine. (Examples are intestinal
antibacterial or antiseptic agents and intestinal
vermifuges.) As in the case of repeat-action and other
controlled-release dosage forms, the influence of altering
the release profile of the drug on total drug bioavailability,
distribution, and pharmacokinetics must be investigated.

Rate limiting step of

Controlled drug delivery

Rate limiting step of

conventional dosage form

System

Fig 2: Schematic representing the rate limiting step in the

design of controlled drug delivery system

Objective
The obj ective of the present study is to develop
competitive enteric sustained release tablets of
Didanosine for a period of 12hrs, by preparing granules
using different polymers and study the effect of polymers
on their release pattern.

PHARMANEST - An International Journal of Advances In Pharmaceutical Sciences

Vol. 2 (1) January - February 2011 www.pharmanest.net

41

PHARMANEST

ISSN 0976 - 3090 (Print) 2231 - 0541 (Online)

PREFORMULATION STUDIES

MANUFACTURING PROCEDURE OF ENTERIC COATED

Preformulation testing is an investigation of physical

properties of a drug substances alone and when combined
with excipients. It is the first step in the rational
development of dosage forms.

TABLETS

Identification of drug

were passed through #40 mesh and added to the above

The identification of drug was done by Differential scaning

chromatography (DSC). The DSC spectrum of pure drug
didanosine is shown

granular material and blended for 5 min and prepare damp

DSC Studies method

DSC studies(9) were performed for pure drug. Accurately
weighed 5-6 mg samples were hermetically sealed in
aluminium pans and heated at constant rate of 10oC/min
over a temperature range of 40 to 300 oC. Inert
atmosphere was maintained by purging nitrogen gas at a
flow rate of 50ml/min. Indium/zinc standards were used
to calibrate the temperature and enthalpy scale.

Weighing & Sifting: Accurately weigh requires quantity of

didanosine and sifted through #40 mesh.
Mixing: Ethylcellulose, Microcrystalline cellulose, povidone

mass and finally pass through #24 mesh and allow the
granules at 40C.
Lubrication: Magnesium stearate and aerosil were passed
through 60#and added to the above blended material.
Compression: compress the blend into tablets with punch
size of 20 x 7mm rod shaped
Coating: Tablets are taken in a coating pan and coating
have done.
Preparation of coating solution: Take required quantity of
isopropyl alcohol stir with propeller stirrer to form vortex.
Add quantity of Eudragit in vortex stir for 25 mins. Maintain
the solution without air bubbles then use the solution for

EXPERIMENTAL

coating. Quantity of tablets to be coated is 100 Tab

FORMULAT ION OF DI DANO SINE ENT ERIC

COATED SUSTAINED RELEASE TABLETS

PHARMANEST - An International Journal of Advances In Pharmaceutical Sciences

Vol. 2 (1) January - February 2011 www.pharmanest.net

42

PHARMANEST

ISSN 0976 - 3090 (Print) 2231 - 0541 (Online)

DISSOLUTION TEST
Many procedures have been proposed for determining
dissolutions rates from solid dosage form. In the present
investigation 8 baskets dissolutions apparatus investigated
that drug release from the tablets. Dissolution studies(10)
were performed using USP standard dissolution
apparatus at 37 0.5C.Using one tablet at a time in a
vessel. The basket was immersed in 900ml of dissolution
medium and rotated at 50 rpm. The dissolution Media
used was initially 0.1N Hcl up to 2hrs, then continuation
with fasted buffer having pH6.8
During the test 10ml of the sample was withdrawn at
specific time intervals 1, 2, 4, 6, 8, 10, 12 hrs after each
withdrawal, same volume of fresh dissolution medium was
added to maintained sink conditions. Different aliquots
were suitably diluted. The absorbance was measured in
the UV spectrophotometer at max 248nm.
In the present study (In house specification) apparatus
I was for the determination of drug release

VII. STABILITY STUDY

For all the pharmaceutical dosage forms it is important to
determine the stability of the dosage form. This will include
storage at both normal and exaggerated temperature
conditions, with the necessary extrapolations to ensure
the product will, over its designed shelf life, provide
medication for absorption at the same rate as when
originally formulated. The design of the formal stability
studies for the drug product should be based on the
knowledge of the behavior and properties of the drug
substance and formal stability studies on the drug
substance

PHARMANEST - An International Journal of Advances In Pharmaceutical Sciences

Vol. 2 (1) January - February 2011 www.pharmanest.net

43

PHARMANEST

ISSN 0976 - 3090 (Print) 2231 - 0541 (Online)

Method
Ten tablets were individually wrapped using aluminum foil
and packed in ambered color screw cap bottle and put at
above specified condition in incubator for 2 months. After
two months tablets were evaluated for content uniformity
and invitro drug release.
Observation
Physical evaluation report

No significant difference was observed in the weight of

individual tablets from the average weight. The data of
uniformity of content indicated that tablets of all batches
had drug content within pharmacopoeia limits. The
hardness of tablets of all batches are in acceptable limits,
which shows in the literature. All the formulation showed
% friability less than 1% that indicates ability of tablets of
withstands shocks, which may encounter. No significant
difference was observed in the thickness of individual
tablet from the average weight.
Standard calibration curve of Didanosine tablets were
prepared in two media i.e 0.1N Hcl and phosphate buffer
6.8pH. Correlation coefficient values indicate the linear
correlation between concentration and absorbance and
following lamberts beers law.

RESULTS AND DISCUSSION

The procured sample of Didanosine was tested for its
identification. The manufacturer also was confirmed of
quality and purity of sample.
The drug excipients compatibility was done at
accelerated temperature 25oC/55% 5% and 30o C/
60% 5% relative humidity. Opened and closed vial
methods were used. The result doesnt show any physical
change to the mixture after 30 days. This fact concluded
that the drug and Excipient are compatible with each other.
The Enteric coated sustained release tablet of Dedanosine
were prepared by wet granulation method, They were
evaluated for weight variation, drug content, friability,
hardness, and thickness for all batches (F1 to F9).

The release of Didanosine from enteric coated sustained

release tablet of various formulations varied according to
the ratio and degree of the polymer. In case of tablet of
F1 containing Drug & 10% Ethyl cellulose Med 70p, with
povidone and MCC shows the 91% of drug release with
in 8hrs, In case of Formulation F2 containing Drug and
15%Ethyl cellulose Med 70 P with povidone, MCC shows
maximum release in 8hrs only,.
In case of tablet of F3 containing Drug & 20% Ethyl
cellulose Med 70p, with povidone and MCC shows the
95% of drug release with in 10hrs, In case of Formulation
F4 containing Drug and 10%Ethyl cellulose Std 100 P
with povidone, MCC shows maximum release in 10hrs
only, In case of tablet of F5 containing Drug & 15% Ethyl
cellulose Std 100p, with povidone and MCC shows the
96% of drug release with in 10hrs, In case of Formulation
F6 containing Drug & Ethyl cellulose Std 100FP 20%,
povidone, MCC, shows accurate results that is drug
release up to 12hrs. In case of Formulation F7 containing
Drug and 10%Ethyl cellulose Med 50 P with povidone,
MCC shows maximum release in 10hrs only, In case of
Formulation F8 containing Drug and 15%Ethyl cellulose
Med 50 P with povidone, MCC shows maximum release
in 10hrs only, In case of Formulation F9 containing Drug
and 12%Ethyl cellulose Med 50 P with povidone, MCC
shows maximum release in 10hrs only, from the above
data In case of tablet of F6 containing Drug & Ethyl
cellulose Std 100FP 20%, povidone, MCC, shows
accurate results that is drug release up to 12hrs.
No significant change was observed in Formulation-6 from
the stability study results, After the stability study all
physical and dissolution test and assay have done and
shows no change observed.

PHARMANEST - An International Journal of Advances In Pharmaceutical Sciences

Vol. 2 (1) January - February 2011 www.pharmanest.net

44

ISSN 0976 - 3090 (Print) 2231 - 0541 (Online)

PHARMANEST

REFFERENCES
1. Rubinstein, M. H. Tablets. In Pharmaceutics: The
Scienceof dosage form design. Aulton, M. E. Ed.;
Churchill Livingstone: New York, 2000, pp. 305.
2. Chien, Y. W. Rate control drug delivery systems:
controlled release vs. sustained release. Med. Prog.
Techn. 1989, 15, 21-46.
3. Chein, Y. W. Novel Drug Delivery System Vol. 14,
Marcel Dekker Inc. New York. 1992, pp. 139-196.
4. Grass, G. M.; Robinson, J. R. Sustained and
Controlled release drug delivery systems. In Modern
Pharmaceutics. Vol. 40; 2nd ed., Banker, G. S.;
Rhodes, C. T.; Eds.; Marcel Dekker Inc: New York.
1990, pp. 635-638.
5. Lordi, N. G. Sustained release dosage forms. In The
Theory and Practice of Industrial Pharmacy. 3rd ed.,
Lachman, L.; Lieberman, H. A.; Kanig J. L. Eds.;
Lea and Febiger: Philadelphia, 1991, pp. 430-435.
6. Robinson, R.; Lee, V. H. Influence of Drug Properties
and route of Drug Administration on the design of
sustained and controlled release drug delivery
system. In Controlled Drug Delivery Fundamentals
and Applications. Vol. 29; 3rd ed., Robinson, R.;
Lee, V. H.; Eds.; Marcel Dekker Inc: New York, 1995,
pp. 3-35.
7. Lee, V. H. L.; Yang, J. J. Oral Drug Delivery. In Drug
Delivery and Targeting. Hillery, A. M.; Llyod, A.W.;
Swarbrick, J.; Eds. Taylor and Francis: London and
New York, 2001, pp.165- 168.
8. Hui, Ho- Wah; Robinson, J. R. Design and
Fabrication of Oral controlled release release drug
delivery systems. In Controlled Drug Delivery
Fundamentals and Applications. Vol. 29; 3rd ed.,
Robinson, R.; Lee, V. H.; Eds.; Marcel Dekker Inc:
New York, 1995, pp. 373-378
9. Aulton, M. E. Pharmaceutics The Science of Dosage
Form Design. Churchill Livingstone. 2002, 2nd ed.,
pp. 414-418.
10. Shargel, L.; Wu- Pong, S.; Yu, A. B. Applied
Biopharmaceutics and Pharmacokinetics. 5th ed.,
Mc. Graw Hill, 2005, pp. 515-520.10.

Address For Corresposdence:

vivekpharmaceutics@gmail.com
PHARMANEST - An International Journal of Advances In Pharmaceutical Sciences

Vol. 2 (1) January - February 2011 www.pharmanest.net

45