WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

Betala et al. World Journal of Pharmacy and Pharmaceutical Sciences

SJIF Impact Factor 6.647

Volume 6, Issue 11, 1497-1507 Research Article ISSN 2278 – 4357

FORMULATION & EVALUATION OF SUSTAINED RELEASE

MICROSPHERES OF PROPRANOLOL

Surendranath Betala*, M. Mohan Varma1 and K. Abbulu2

*Sri Vasavi Institute of Pharmaceutical Sciences, Tadepalligudem, Andrapradesh, India.

1
Sri Vishnu College of Pharmacy, Bhimavaram, Andrapradesh, India.
2
CMR College of Pharmacy, Hyderabad, Telangana, India.

Article Received on
ABSTRACT
18 Sept. 2017, Formulated Propranalol sustained release microspheres. Microspheres
Revised on 08 October 2017,
Accepted on 29 October 2017 are prepared by Ionic-Gelation method using Hydroxy Propyl Methyl
DOI: 10.20959/wjpps201711-10511 Cellulose (HPMC), Ethyl cellulose and Sodium CMC for sustained
release in view to prolong drug release. Propranalol is an adreno
*Corresponding Author receptor beta blocking agent used in the treatment of hypertension and
Surendranath Betala characterized by high solubility and low permeability which
Sri Vasavi Institute of corresponds to BCS class III drug. Plasma half life ranges from 4 to 7
Pharmaceutical Sciences,
hrs & oral bioavailability is 40-50% hence require frequent oral
Tadepalligudem,
Andrapradesh, India.
administration for adequate treatment of hypertension. Administration
of conventional tablet of Propranalol has been reported to exhibit
fluctuations in plasma drug levels resulting in either manifestation side effects reduction in
drug concentration at receptor site. So that oral sustained dosage form was developed. The
microspheres were evaluated for various characteristics like encapsulation efficiency,
percentage yield, partial size and the In vitro release for 12 hrs. The Microspheres were found
to be discrete, spherical, and free-flowing. The microspheres were uniform in size, and the
microencapsulation efficiency was in the range of 52.5-81.7%. Microspheres had good
spherical geometry.

KEYWORDS: Microspheres, Hypertension, In vitro release, Encapsulation efficiency.

INTRODUCTION
Oral Drug Delivery System: Oral drug delivery has been known for decades as the most
widely utilized route of administration among all the routes that have been explored for the
systemic delivery of drugs via various pharmaceutical products of different dosage forms.

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Betala et al. World Journal of Pharmacy and Pharmaceutical Sciences

SUSTAINED RELEASE DRUG DELIVERY

Sustained release, sustained action, prolonged action controlled release, extended released,
depot release are the terms used to identify drug delivery systems that are designed to
achieve a prolonged therapeutic effect by continuously releasing medication over an extended
period of time after administration of single dose of drug.

MICROSPHERES
Microspheres are small spherical particles, with diameters in the micrometer range (typically
1 μm to 1000 μm (1 mm)). Microspheres are sometimes referred to as microparticles.

DRUG PROFILE
PROPRANOLOL HYDROCHLORIDE
Chemical Name:2-hydroxy-3-(naphthalene-1-yloxy) propy1] (propan-2-y1)amine
hydrochloride
Systematic (IUPAC) Formula:C16H21NO2 . HCl
Mol. mass: 295.80 g/mol

STRUCTURE

Fig.1: Structure of Propranolol hydrochloride.

Description
Propranolol hydrochloride is a stable, white, crystalline solid which is readily soluble in
water and ethanol. Its molecular weight is 295.80.
Physico-chemical Properties:
Melting point: 163-165 o C
Solubility soluble in water, and alcohol; slightly soluble in chloroform; practically in soluble
in ether. As for acid, alkali or organic solvent like diethyl ether.
Spectral Properties: λmax (Propranolol): 289.

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Betala et al. World Journal of Pharmacy and Pharmaceutical Sciences

MATERIALS AND METHODS

Table 1: List of Materials used for the study
S.NO INGREDIENTS SUPPLIER
Indian pharmaceutical
1 Propranolol
Solutions, HYD
Ozone International,
2 Hydroxyl propyl methyl cellulose K100M
Mumbai.
Ozone International,
3 Sodium carboxy methyl cellulose
Mumbai.
Loba Chemie Pvt Ltd.,
4 Ethyl cellulose
Mumbai.
Sd Fine-Chem Limited,
5 Calcium chloride
Mumbai.
Loba Chemie Pvt Ltd.,
6 Sodium alginate
Mumbai.

FORMULATION OF SUSTAINED RELEASE MICROSPHERES

PROCEDURE: The following steps involved in preparation of Atenolol microspheres.

Preparation of Polymer Solution by dissolving in distilled water.

Dissolve Drug (Propranolol) in above Solution.

Sonicate the Drug-Polymer Solution for proper mixing.

Above solution was added drop wise by a 26G hypodermic needle into 50ml of
5% w/v CaCl2 solution.

Formed Propranolol Microspheres were stirred in the cross linking agent for 1hr
at 100rpm.

Wash the Microspheres with de-ionized water and dried at 80oC for 2hr.

Transfer prepared Microspheres to desiccators to maintain the constant Humidity

conditions.

Fig. 2: Flow chart for process of Formulation.

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All Formulations were prepared by Ionic Gelation method using different polymers.

Table No. 2: Trail formulations composition.

HPMC Ethyl Sodium
Trail Propranolol Sodium Cacl2
S.No: K100M Cellulose Alginate
Formulations (mg) CMC (mg) %(W/V)
(mg) (mg) (mg)
1 F1 50 _ 50 _ 1000 5
2 F2 50 _ 100 _ 1000 5
3 F3 50 _ _ 50 1000 5
4 F4 50 100 _ _ 1000 5
5 F5 50 50 _ _ 1000 5

RESULTS AND DISCUSSIONS

PREFORMULATION STUDIES
Drug excipient compatibility studies
The compatibility of drug and formulation components is important prerequisite before
formulation. It is therefore necessary to confirm that the drug does not react with the
polymers and excipients under experimental conditions and affect the shelf life of product or
any other unwanted effects on the formulation.

The compatibility study between the drug and the polymer was done by I.R studies. No major
peak shift was observed in the I.R graphs in major functional groups. Based on the
compatibility studies obtained by I.R studies, the polymer carbopol 940 was taken for the
optimization of the formulation, which is compatible with the drug.

EVALUATION TESTS
PARTICLE SIZE
SEM photograph of formulated Microspheres

Fig. 3: SEM of formulated Microspheres.

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IN-VITRO DISSOLUTION DATA: DISSOLUTION KINETICS

Table. 4: Percentage drug release for optimized formulation.
Time(hrs) Absorbance % Cumulative drug release
0 0 0
1 0.127 45.1
2 0.140 54.5
3 0.237 63.7
4 0.246 64.3
5 0.311 66.9
6 0.324 67.2
7 0.372 69.1
8 0.446 72.2
9 0.508 74.6
10 0.573 77.4
11 0.643 80.3
12 0.764 85.2

Fig.4: Dissolution profile of formulation F-5.

COMPARATIVE DISSOLUTION PROFILE

Table No. 5: Comparative dissolution profile for different formulations F1-f5.
F-1 % F-2 % F-3 % F-4 % F-5 %
Time(hrs)
CDR CDR CDR CDR CDR
0 0 0 0 0 0
1 32.4 36.0 41.4 45.0 45.1
2 36.0 45.0 50.4 50.4 54.5
3 44.1 53.1 59.4 62.6 63.7
4 45.0 53.4 61.2 63.0 64.3
5 46.9 54.0 61.7 64.2 66.9
6 48.6 54.3 62.1 64.8 67.2
7 49.8 55.0 63.0 66.6 69.1
8 51.1 56.3 65.1 68.0 72.2
9 52.0 57.6 66.4 69.3 74.6
10 52.7 59.4 67.1 70.9 77.4
11 54.0 60.5 68.4 72.5 80.3
12 55.6 62.1 68.3 75.0 85.2

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Fig.5: Comparative dissolution profile for formulation F1-F5.

Inference: From the above fig the dissolution profile for the formulation F-5 was found to be
have the more cumulative % drug release.

DISSOLUTION- APPLICATION OF KINETICS OF F-5

Table:6 Application of kinetics for dissolution profile of formulation F-5.
Log % Log % drug Square
TIME(hr) %CDR Log time
CDR unreleased root time
0 0 1 1.995 0 1
1 45.1 1.653 1.740 1 0
2 54.5 1.732 1.662 1.414 0.3010
3 63.7 1.804 1.559 1.732 0.4771
4 64.3 1.806 1.556 2 0.6020
5 66.9 1.825 1.519 2.236 0.6989
6 67.2 1.827 1.515 2.449 0.7781
7 69.1 1.835 1.499 2.645 0.8450
8 72.2 1.858 1.444 2.828 0.9030
9 74.6 1.872 1.404 3 0.9542
10 77.4 1.888 1.354 3.167 1
11 80.3 1.904 1.294 3.316 1.0413
12 85.2 1.930 1.170 3.464 1.0791

ZERO ORDER PLOT

Figure:6 Zero order plot for optimized formulation F-5.

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FIRST ORDER PLOT

Figure:7 First order plot for optimized formulation F-5.

Inference: From the above graph R2 value is (0.931) and for zero order plot R2value is
(0.919) which indicates that the order of release was first order.

HIGUCHI’S PLOT

Figure:8 Higuchi’s plot for optimized formulation F-5.

KORSEMEYER-PEPPAS PLOT

Figure:9 Korsemeyer- Peppas plot for optimized formulation F-5.

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Inference: As per the above plot the R2 value for Higuchi (0.919) and for Korsemeyer –
peppas plot (0.961), showing that the mechanism of drug release from the formula was found
to be diffusion controlled release.

Stability studies
The accelerated stability study for the formulation at 40 ± 20 C and 75 ± 5 % RH was
conducted for the 6 months, which includes the testing of parameters like identification of
physical characters, identified by IR studies, dissolution profile and assay throughout period.

CONCLUSION
Thus, Microspheres with a coat consisting of Sodium alginate and other polymers (Sodium
CMC, HPMC K100M and Ethyl Cellulose) could be prepared by an Ionic gelation process.
The microspheres exhibited good sustained release in an in vitro test. Propranolol release
from these sustained release microspheres was slow and extended over a longer period of
time (12hrs) and depended on composition of the coat. Drug release was diffusion controlled
and followed zero-order kinetics. In the in vitro evaluation, Sodium alginate-HPMC K100M
microspheres could sustain the drug release over a 12-hour period. . Based on results the best
formulation F5 can successfully employed as a controlled release drug delivery system.
These sustained release microspheres are thus suitable for oral sustained release of
Propranolol.
 FTIR studies revealed no interactions between the drug and polymers used.
 Formulated Microspheres gave satisfactory result for various physico-chemical
evaluations like physical appearance, surface morphology, entrapment efficiency,
percentage drug loading and in vitro drug release.
 The prepared beads showed required drug release in about 12hrs.
 From the research, it can be concluded that Propranolol can be formulated as
microspheres for the desired use in treatment of Hypertension.

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