Research Journal of Pharmaceutical Dosage Forms and Technology.

8(1): January-March, 2016

ISSN 0975-234X (Print) www.anvpublication.org

0975-4377 (online)

RESEARCH ARTICLE

Formulation and Evaluation of Aqueous Enteric Coated Delayed Release

Omeprazole Pellets

Viswanadham Manasa1, K.Vanitha1, M. Venkataswamy1, P. Prabhakar1, Alluri Ramesh2

Department of Pharmaceutics1, Pharmacology2, Vishnu Institute of Pharmaceutical Education and Research,
Vishnupur, Narsapur
*Corresponding Author E-mail: [email protected]

ABSTRACT:
The main objective of the present study was to develop and optimize enteric coated pellets of Omeprazole using
enteric polymers like hydroxyl propylmethylcellulose phthalate. Characterization of the drug was carried out by
performing the melting point, identification test by FTIR, solubility, loss on drying and assay parameteres. Then
drug-excipient interaction studies were carried out using FTIR. Six formulations of pellets were prepared, from
which F5 was chosen for further coating process. Then F5 formulation was sub-coated with HPMC E5 and
enteric coated using HPMCP-55.All the formulations were evaluated for their physico-chemical parameters like
assay, drug content and dissolution, etc. The in vitro drug release study was performed for the prepared
formulations. From the in vitro drug release study, it was found that all the formulations demonstrated excellent
physical resistance to the acid medium after 2 hour and the drug release was found to be within specified limits.
Formulation subjected to stability studies were checked for physical appearance, drug content and dissolution for
3 months.

KEYWORDS: Aqueous enteric coated, delayed release Omeprazole pellets,

INTRODUCTION:
Oral administration1,2 of drugs has been the most
common and preferred route of delivery of most
therapeutic agents due to good patient acceptance, ease
of administration, examples Tablets, capsules, liquid
solutions, etc. The absorption rate varies from the
stomach to the intestine owing to the increased surface
area (about 4500cm²), the intestinal mucosa and greater
blood flow (1000 ml/min) through the intestinal
capillaries compared to the gastric capillaries. It is also
known that some drugs possessing pH dependent
stability which are not stable in acidic environment
(Stomach). Various techniques have been developed to
overcome this stability problem. One out of them is
development of enteric coated products. These enteric
Received on 13.10.2015 Modified on 10.12.2015 coated dosage forms resist the acidic environment of the
Accepted on 25.12.2015 ©A&V Publications All right reserved stomach and allow disintegration in the higher pH
Res. J. Pharm. Dosage Form. & Tech. 8(1): Jan.-Mar. 2016; Page 01-04
DOI: 10.5958/0975-4377.2016.00002.1 environment of the intestinal fluid. The enteric coating
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 Research Journal of Pharmaceutical Dosage Forms and Technology. 8(1): January-March, 2016

on a solid dosage form can also be used for site-specific MATERIALS AND METHODOLOGY:
drug delivery of a therapeutic agent to the intestinal List of materials:
region. Omeprazole, Mannitol, sucrose, sodium lauryl sulphate,
Disodium hydrogen phosphate, Calcium carbonate,
Modified release systems2,3 designed to reduce the HPMC E5, HPMC P-55, Titanium dioxide, Sodium
frequency of dosing by modifying the rate of drug methyl paraben, Sodium propyl paraben, PEG-6000,
absorption have been available from many years. Purified water.
Intestinal release systems: A drug may be enteric coated
for intestinal release for several known reasons such as Method of Formulation7,8
to prevent gastric irritation, prevent destabilization in Omeprazole enteric coated pellets were prepared by
gastric pH, etc. Colonic release systems: Drugs are Spheronization method and are enteric coated using
poorly absorbed through colon but may be delivered to aqueous enteric coating solution.
such a site for two reasons- Local action in the treatment
of ulcerative colitis and Systemic absorption of protein Preparation of Omeprazole enteric coated pellets:
and peptide drugs. Drug loading: Specified quantity of non-pareil seeds
were accurately weighed and dispensed. 500ml of
The most advantages of pelletization are improved purified water is taken in a beaker and kept for stirring
appearance of the product and the core is under a mechanical stirrer. Specified quantities of
pharmaceutically elegant. Pelletization3,4 offers mannitol, sucrose (diluent), di-sodium hydrogen
flexibility in dosage form design and development. phosphate were added slowly to form a uniform
Pellets are less susceptible to dose dumping. It reduces suspension. Specified quantity of Omeprazole is added
localized concentration of irritative drugs. It improves and stirring is continued further. To this suspension,
safety and efficacy of a drug. Pellets offer reduced sodium lauryl sulfate and calcium carbonate are added
variation in gastric emptying rate and transit time. Pellets followed by sodium methyl paraben and sodium propyl
disperse freely in G.I.T. and invariably maximize drug paraben. The non pareil seeds were coated using coating
absorption and also reduce peak plasma fluctuation. pan. The pellets are dried and the dried pellets were
Pellets ensure improved flow properties in formulation collected.
development. Coating of pellets can be done with a) Sub coating stage: 500ml of purified water is taken
different polymers to enable controlled release of the in a beaker and kept for stirring under a mechanical
drug. In case of immediate Release Products larger stirrer. Specified quantity of HPMC E5 was added
surface area of pellets enables better distribution. slowly to form a uniform suspension. Drug loaded
Chemically incompatible products can be formed into pellets were coated with the above suspension using
pellets & delivered in a single dose by encapsulating Fluidized bed coater (FBC). The dried pellets were
them. Varied applications are possible in the pellet form. then collected.
eg: sustained release. Pellets ensure improved flow
properties, and flexibility in formulation development b) Enteric coating stage: 500ml of purified water was
and manufacture. Pellets may have varied applications in taken in a beaker and kept for stirring under a
varied industries. It just requires an innovative bend to mechanical stirrer. Specified quantities of enteric
use it to derive maximum profitability. The smooth polymer i.e., HPMCP-55 and plasticizer i.e., PEG-
surface & the uniform size of the pellets allow uniform 6000 were added slowly to form a uniform
coating not only for each pellet but also to whole batch suspension. Stirring was continued until the
itself. suspension is completely formed. Barrier coated
pellets were coated with this prepared suspension
Omeprazole5,6 is a highly effective inhibitor of gastric using Fluidized bed coater. Dried pellets were
acid secretion used in the therapy of stomach ulcers and collected and evaluated.
Zollinger-Ellison syndrome. Omeprazole belongs to a
class of anti- secretory compounds, the substituted Aqueous enteric coating solution preparation9
benzimidazoles that suppresses gastric acid secretion by Table no 1. List of ingredients
specific inhibition of the H+/K+ ATPase enzyme system S.no Ingredients Quantity
at the surface of the gastric parietal cell. 1. HPMCP-55 60gm (6%)
2. Ammonia Quantity sufficient
3. Water 1000ml

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 Research Journal of Pharmaceutical Dosage Forms and Technology. 8(1): January-March, 2016

Evaluation Parameters Calculation10:

The following evaluation tests were performed to the A = At/As*Ws/50*3/100*50/Wt*100/3*100
formulated pellets.
Where, At = Absorbance of the sample preparation, As =
Moisture content (or) Water content by KF: Absorbance of the standard preparation
Take around 50ml of methanol in titration vessel of Karl Ws = Weight of the standard taken in mg, Wt = Weight
Fischer titrator and titrate with Karl Fischer reagent to of the sample taken in mg
end point. In a dry motor grind the pellets to fine
powder. Weigh accurately about 0.5g of the sample, In-vitro Dissolution11
transfer quickly to the titration vessel, stir to dissolve and Procedure:
titrate with Karl Fischer reagent to end point. Dissolution studies for gastric resistance: Transfer
900ml of 0.1N HCl in each vessel of the dissolution
Calculation: apparatus and adjust the temperature to 37°C +
Moisture content = V*F*100/weight of sample in mg 0.5°C.Weigh and transfer the pellets equivalent to 20mg
of Omeprazole individually in each of the 6 dissolution
Where, F = factor of Karl Fischer reagent, V = volume in flasks, containing 900ml of 0.1N HCl, Note the time.
ml of Karl Fischer reagent consumed for sample After two hours, collect the pellets sample from each
titration. vessel and 0.1N NaOH is added for neutralization. Filter
the solution through filter media. Pipette out 5ml in a
Assay: 50ml volumetric flask and make up the volume with
Standard preparation: 0.1N NaOH. The samples were analyzed using UV-
Weigh accurately about 20mg of Omeprazole working Spectrophotometer at 302nm.
standard into a 50ml volumetric flask and add 50ml of
0.1N NaoH. Shake well and make up the volume with Dissolution studies in phosphate buffer12 pH6.8:
0.1N NaoH. Pipette out 3ml of this solution into a 100ml Transfer 900ml of phosphate buffer PH 6.8in each vessel
volumetric flask, dilute it to volume with 0.1N NaoH of the dissolution apparatus and adjust the temperature to
and mix well. 37°C + 0.5°C. Transfer the pellets which were
previously tested for gastric resistance into the vessels.
Sample preparation: Run the apparatus for 45 minutes. After 45 minutes,
Weigh accurately 20mg drug equivalent pellets in a draw 10ml of the sample from each vessel, filter the
100ml volumetric flask, add 0.1N NaoH and make up sample. Analyze the samples using UV-
the volume. Filter the solution through Whatman filter Spectrophotometer at 302nm.
paper. Pipette out 5ml of the filtrate into a 50ml
volumetric flask. Dilute to volume with 0.1N NaOH. Calculation: The percentage drug release can be
calculated by the following equation,
Procedure: Scan the solution of both standard and
sample preparation against blank preparation between Percentage drug release = At/As*W/Ws*100/Assay*P
200-400 nm and measure the absorbance for both
standard and sample at 302nm. Where, At = Absorbance of sample, As = Absorbance
of standard, W = weight of standard
Ws = weight of sample, P = potency

RESULTS AND DISCUSSION:

IR spectrum:

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 Research Journal of Pharmaceutical Dosage Forms and Technology. 8(1): January-March, 2016

Table no. 2: Formulation: Six formulations of pellets were prepared and from that
S.No F1 F2 F3 F4 F5 F6 formulation F5 was selected, as its results were found to
HMPCP-55 6% 6% 6% 6% 6% 6%
Ammonia 15ml 13ml 12ml 11ml 10ml 9ml be convincing compared to all other formulations
Water(ml) 1000 1000 1000 1000 1000 1000
PEG-6000 6.5g 6.5g 6.5g 6.5g 6.5g 6.5g Table no. 3: Physical properties of enteric coated pellets
Parameters F1 F2 F3 F4 F5 F6
Bulk density (gm/cm³) 0.82 0.84 0.87 0.92 0.8 0.81
Moisture content (%) 1.94 1.96 1.94 1.92 1.9 1.93

Table no. 4: Dissolution studies:

Time F1 F2 F3 F4 F5 F6
0 0 0 0 0 0 0
15min 3.15% 2.73% 2.57% 1.25% 0.85% 0.92%
30min 5.12% 3.85% 3.26% 2.52% 2.18% 2.02%
1 Hr 6.95% 5.84% 5.68% 3.48% 3.05% 2.98%
2Hr (0.1N HCl) 9.01% 7.66% 7.31% 4.43% 4.21% 4.24%
2Hr 45min (buffer) 81.40% 83.28% 84.24% 94.28% 95.81% 94.98%

The release kinetics was evaluated for F5 formulation REFERENCES:

using linear regression method. The best fit model was 1. Lachman L, Liberman HA, Kanig JL. The Theory and Practice of
observed to be Korsemeyer-Peppas. The value of n was Industrial Pharmacy, Varghese Publishing House, Bombay, 3rd ed,
1991.
found to be 0.92, indicating super case II transport drug 2. Brahmankar D M, Jaiswal S B, A treatise of Biopharmaceutics and
release. Pharmacokinetics, Vallabh Prakashan, 01, 1995.
Table no.5:release kinetics of formulation F5 3. Banker, G.S, and Rhodes C.T., 1996, Modern Pharmaceutics,
Formula Zero First Higuchi Peppas Best fit 3rded., Marcel Dekker, New York pp.
tion order order model 4. Korsmeyer R, Gurny R, Peppas N. Mechanisms of solute release
F5 0.45 0.42 0.37 0.92 Peppas from porous hydrophilic polymers. Int. J. Pharm. 1983;15:25–35.
doi: 10.1016/0378-5173(83)90064-9. [Cross Ref]
5. Rupesh S. Kamble, Archana D. Kajale, Keshao P. Giradkar B. V.
Bakade, M. A.Channawar, A. V. Chandewar. Formulation and
Stability Studies: Development of Enteric Coated Dosage form using Ketorolac
Stability Studies were carried out at 40°C ± 2°C / 75% ± Tromethamine. International Journal of Pharmaceutical Research
5% RH for f5 formulation for 3 months. and Development, 2010; 2(8)
6. D.V. Gowda, Rajesh. N, H.G. Shivakumar, Siddaramaiah and
Nawaz Mahammed. Development and Evaluation of Oral
Results of stability studies: Controlled Release from Aceclofenac Sodium Pellets. Online
There was no change observed. So the prepared f5 Published (2010).
formulation was stable. 7. Murat Turkoglu, Hakan Varol, Mine C¸ Elikok. Tableting and
stability evaluation of enteric-coated Omeprazole pellets.
Table no.6 : Stability studies of formulation F5 European Journal of Pharmaceutics and Biopharmaceutics. 2004;
Time Dissolution (0.1N HCl) Dissolution (Phosphate buffer) 57
0 month 4.21% 95.81% 8. Anroop B Nair, Rachna Gupta, Rachna Kumria, Shery Jacob and
1 month 4.19% 95.74% Mahesh Attimarad. Formulation and Evaluation of Enteric Coated
2 months 4.19% 95.65% Tablets of Proton Pump Inhibitor. Journal of Basic and Clinical
3 months 4.15% 95.27% Pharmacy.
9. Rabia Bushra, Muhammad Harris Shoaib, Nousheen Aslam, Zafar
Alam Mehmood, Durriya Hashmat. Enteric coating of Ibuprofen
CONCLUSION: tablets (200 mg) using an aqueous dispersion system. Brazilian
In the present study, Omeprazole enteric coated pellets Journal of Pharmaceutical Sciences, 2010; 46(1)
10. Lehman K. Mcginity J W: Aqueous Polymeric coatings for
were prepared using enteric coating polymer like Pharmaceutical dosage forms. New York: Marcel Dekker; 1989,
hydroxyl propyl methyl cellulose phthalate. From this 153-247.
study it can be concluded that Omeprazole enteric coated 11. Porter S C, Bruno C H. Coating of Pharmaceutical Dosage Forms.
pellets prepared by HPMCP-55 showed better Int. Daily J. 1990; 14: 505-515.
12. Kathija Mufeeda, Ravikumar, Nureesha Ayshath, Narayanaswamy
performance than the pellets prepared using other enteric V.B. Formulation and Evaluation of Controlled Release Matrix
polymers like CAP, HPMC, etc. The formulation F5 was Tablets of Sotalol. Research Journal of Pharmaceutical Dosage
considered optimum because it showed negligible drug Forms and Technology. 2015, Volume7, Issue2, 134-142.
release in acidic medium and the drug release in the 13. Rowe R C, Sheskey P J, Weller P J. Handbook of Pharmaceutical
phosphate buffer (pH 6.8) was found to be almost Excipients, 4th Ed. Chicago: American Pharmaceutical
Association; 2003.
complete. The stability studies of the selected
formulation showed that the product was stable
throughout the study period (3months).
4