Formulation and
Evaluation of Oral Controlled Release Matrix Tablets of Propranolol
Hydrochloride
Dr. Y. Krishna Reddy*, Ch.
Asha
Department of Indutrial
Pharmacy, Nalanda College of Pharmacy, Jawaharlal Nehru Technological
University, Hyderabad, Telangana.
*Corresponding Author E-mail: rajinisuralabs1@gmail.com
ABSTRACT:
The aim of the present study
was to develop Propranolol Hydrochloride Oral Controlled release tablets to
maintain constant therapeutic levels of the drug for over 12 hrs. Locust bean
gum, Kollidon SR, Karaya gum were used as polymers. All the formulations were
passed various physicochemical evaluation parameters such as Bulk Density,
Tapped Density, Carr’s Index, Hausner’s Ratio, Angle of Repose, Weight
Variation, Hardness, Thickness, Friability and Drug Content. From the
dissolution studies it was evident that the formulation F7 showed better and
desired drug release pattern i.e., 98.56 % in 12 hours. It contains the Karaya
gum as polymer. It followed Zero order release kinetics mechanism.
KEYWORDS: Propranolol
Hydrochloride, Locust bean gum, Kollidon SR, Karaya gum and Controlled release
tablets.
INTRODUCTION:
Controlled release
tablets are commonly taken only once or twice daily, compared with counterpart
conventional forms that may have to take three or four times daily to achieve
the same therapeutic effect. The advantage of administering a single dose of a
drug that is released over an extended period of time to maintain a
near-constant or uniform blood level of a drug often translates into
better patient compliance, as well as enhanced clinical efficacy of the
drug for its intended use.
The first
Controlled release tablets were made by Howard Press in New Jersy in the early
1950's. The first tablets released under his process patent were called
'Nitroglyn' and made under license by Key Corp. in Florida.
Controlled release,
prolonged release, modified release, extended release or depot formulations are
terms used to identify drug delivery systems that are designed to achieve or
extend therapeutic effect by continuously releasing medication over an extended
period of time after administration of a single dose.
The goal in
designing Controlled or Controlled delivery systems is to reduce the frequency
of the dosing or to increase effectiveness of the drug by localization at the
site of action, reducing the dose required or providing uniform drug delivery.
So, Controlled release dosage form is a dosage form that release one or more
drugs continuously in predetermined pattern for a fixed period of time, either
systemically or to a specified target organ.
Controlled release
dosage forms provide a better control of plasma drug levels, less dosage
frequency, less side effect, increased efficacy and constant delivery. There
are certain considerations for the preparation of extended release
formulations:
·
If the active compound has a long half-life, it is Controlled on its
own,
·
If the pharmacological activity of the active is not directly related
to its blood levels,
·
If the absorption of the drug involves an active transport and
·
If the active compound has very short half-life then it would require a
large amount of drug to maintain a prolonged effective dose.
The above factors
need serious review prior to design.
Introduction of
matrix tablet as Controlled release (SR) has given a new breakthrough for novel
drug delivery system in the field of Pharmaceutical technology. It excludes
complex production procedures such as coating and Pelletization during
manufacturing and drug release rate from the dosage form is controlled mainly
by the type and proportion of polymer used in the preparations. Hydrophilic
polymer matrix is widely used for formulating an SR dosage form. Because of
increased complication and expense involved in marketing of new drug entities,
has focused greater attention on development of Controlled release or
controlled release drug delivery systems. Matrix systems are widely used for
the purpose of Controlled release. It is the release system which prolongs and
controls the release of the drug that is dissolved or dispersed.
In fact, a matrix
is defined as a well-mixed composite of one or more drugs with gelling agent
i.e. hydrophilic polymers. By the Controlled release method therapeutically
effective concentration can be achieved in the systemic circulation over an
extended period of time, thus achieving better compliance of patients. Numerous
SR oral dosage forms such as membrane controlled system, matrices with water
soluble/insoluble polymers or waxes and osmotic systems have been developed,
intense research has recently focused on the designation of SR systems for
poorly water soluble drugs.
AIM AND OBJECTIVE:
Aim of the Work:
Aim
of the study is to formulate and
evaluate of oral controlled release matrix tablets of Propranolol Hydrochloride
by using different polymers such as Locust bean gum, Kollidon SR and
Karaya gum.
OBJECTIVE OF THE STUDY:
· To improve the
bioavailability
· Reduce the number
of doses and to increase patient compliance it was formulated as controlled
release tablets using various polymers.
· Propranolol is used to treat tremors, angina (chest pain),
hypertension (high blood pressure), heart rhythm disorders, and other heart or
circulatory conditions. It is also used to treat or prevent heart attack, and
to reduce the severity and frequency of migraine headaches.
MATERIALS AND METHODS:
Propranolol
Hydrochloride Procured from Dr. Reddy’s Labs, Provided by SURA LABS,
Dilsukhnagar, Hyderabad. Locust bean gum purchased from Strides Arcolab, Bangalore, Kollidon SR
and Karaya gum purchased from Yarrow chem.
Products, Mumbai. PVP K30 and Magnesium stearate purchased from
Magnesium stearate. Aerosil purchased from Kerry
laboratories.
METHODOLOGY:
Table
1: Formulation composition for tablet
|
INGREDIENTS |
FORMULATION CODES |
||||||||
|
F1 |
F2 |
F3 |
F4 |
F5 |
F6 |
F7 |
F8 |
F9 |
|
|
Propranolol HCL |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Locust Bean gum |
7 |
14 |
21 |
- |
- |
- |
- |
- |
- |
|
Kollidon SR |
- |
- |
- |
7 |
14 |
21 |
- |
- |
- |
|
Karaya gum |
- |
- |
- |
- |
- |
- |
7 |
14 |
21 |
|
PVP K30 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
|
MCC PH 101 |
119 |
112 |
105 |
119 |
112 |
105 |
119 |
112 |
105 |
|
Magnesium stearate |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
|
Aerosil |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
Total tablet weight |
150 |
150 |
150 |
150 |
150 |
150 |
150 |
150 |
150 |
RESULTS AND DISCUSSION:
Analytical Method
Graphs
of Propranolol Hydrochloride was taken in Simulated Gastric fluid (pH 1.2) and
in p H 6.8 phosphate buffer at 266 nm and 268 nm respectively.
Table 2:
Observations for graph of Propranolol Hydrochloride in 0.1N HCl (266nm)
|
CONCENTRATION [µG/ML] |
ABSORBANCE |
|
0 |
0 |
|
10 |
0.128 |
|
20 |
0.254 |
|
30 |
0.368 |
|
40 |
0.489 |
|
50 |
0.601 |
It was found that the estimation of Propranolol Hydrochloride by UV
spectrophotometric method at λmax 266.0nm in 0.1N Hydrochloric
acid had good reproducibility and this method was used in the study. The correlation
coefficient for the standard curve was found to be closer to 1, at the
concentration range, 10-50μg/ml. The regression equation generated was y = 0.012x + 0.006
Figure 1: Standard graph of
Propranolol Hydrochloride in 0.1N HCl
Table 3: Observations for graph of Propranolol
Hydrochloride in p H 6.8 phosphate buffer (268nm)
|
Concentration[µg/ml] |
Absorbance |
|
0 |
0 |
|
10 |
0.126 |
|
20 |
0.245 |
|
30 |
0.363 |
|
40 |
0.486 |
|
50 |
0.596 |
It was found that
the estimation of Propranolol Hydrochloride by UV spectrophotometric method at
λmax 268 nm in pH 6.8 Phosphate buffer. Had good
reproducibility and this method was used in the study. The correlation
coefficient for the standard curve was found to be closer to 1, at the concentration
range, 10-50μg/ml. The regression equation generated was Y = 0.011x +
0.004.
Figure 2: Standard graph of
Propranolol Hydrochloride pH 6.8 phosphate
buffer (268nm)
Pre-formulation parameters of powder blend
Table
4: Pre-formulation parameters of Core blend
|
Formulation Code |
Angle of Repose |
Bulk density (gm/ml) |
Tapped density (gm/ml) |
Carr’s index (%) |
Hausner’s Ratio |
|
F1 |
25 .92’±0.04 |
0.326±0.076 |
0.354±0.06 |
7.998±0.04 |
1.086±0.03 |
|
F2 |
26 .93’±0.06 |
0.350±0.065 |
0.382±0.02 |
8.444±0.02 |
1.090±0.02 |
|
F3 |
27 .82’±0.04 |
0.272±0.076 |
0.314±0.03 |
13.33±0.04 |
1.153±0.08 |
|
F4 |
27 .82’±0.04 |
0.382±0.087 |
0.404±0.06 |
5.547±0.03 |
1.047±0.04 |
|
F5 |
24 .39’±0.02 |
0.259±0.054 |
0.286±0.02 |
9.406±0.02 |
1.103±0.03 |
|
F6 |
25 .07’±0.06 |
0.236±0.06 |
0.266±0.04 |
11.428±0.03 |
1.129±0.05 |
|
F7 |
26 93’±0.03 |
0.324±0.05 |
0.337±0.03 |
8.76±0.04 |
1.041±0.03 |
|
F8 |
27 ±0.04 |
0.37±0.04 |
0.387±0.02 |
5.541±0.06 |
1.045±0.05 |
|
F9 |
24 56’ ±0.02 |
0.37±0.04 |
0.408±0.03 |
9.524±0.07 |
1.095±0.03 |
Tablet
powder blend was subjected to various pre-formulation parameters. The angle of
repose values indicates that the powder blend has good flow properties. The bulk density of
all the formulations was found to be in the range of 0.236±0.06 to 0.382±0.087
(gm/cm3) showing that the powder has good flow properties. The
tapped density of all the formulations was found to be in the range of
0.266±0.04 to 0.408±0.03 showing the powder has good flow properties. The
compressibility index of all the formulations was found to be ranging between
5 to 13 which shows that the powder has good flow properties. All the
formulations has shown the Hausner’s ratio ranging between 1.041±0.03 to
1.153±0.08 indicating the powder has good flow properties.
Quality
Control Parameters For tablets:
TABLE
5: In vitro quality control parameters for tablets
|
Formulation codes |
Average Weight (mg) |
Hardness (kg/cm2) |
Friability (% loss) |
Thickness (mm) |
Drug content (%) |
|
F1 |
145.39 |
5.5 |
0.31 |
3.02 |
99.42 |
|
F2 |
147.52 |
4.2 |
0.58 |
3.48 |
97.34 |
|
F3 |
149.42 |
3.9 |
0.57 |
3.36 |
98.56 |
|
F4 |
144.86 |
4.5 |
0.34 |
3.87 |
99.38 |
|
F5 |
150.05 |
6.1 |
0.48 |
3.23 |
97.65 |
|
F6 |
147.84 |
5.7 |
0.62 |
3.86 |
96.20 |
|
F7 |
145.65 |
4.8 |
0.25 |
3.12 |
99.30 |
|
F8 |
146.21 |
5.3 |
0.19 |
3.28 |
98.63 |
|
F9 |
148.55 |
5.9 |
0.45 |
3.47 |
97.28 |
All
the parameters such as weight variation, friability, hardness, thickness and
drug content were found to be within limits.
In vitro drug release studies:
Table 6: Dissolution Data of
Propranolol Hydrochloride Tablets Prepared with Locust bean gum, Kollidon SR
and Karaya gum in Different Concentrations
|
TIME (H) |
% of Drug Release |
||||||||
|
F1 |
F2 |
F3 |
F4 |
F5 |
F6 |
F7 |
F8 |
F9 |
|
|
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
0.5 |
22.16 |
15.10 |
14.65 |
19.32 |
12.76 |
16.54 |
14.05 |
15.25 |
13.72 |
|
1 |
39.68 |
17.45 |
16.23 |
31.45 |
17.34 |
18.46 |
20.56 |
26.89 |
18.94 |
|
2 |
45.56 |
19.25 |
17.87 |
36.07 |
26.18 |
23.44 |
29.55 |
30.59 |
26.66 |
|
3 |
53.35 |
28.34 |
29.65 |
46.36 |
39.27 |
25.18 |
36.52 |
35.76 |
31.82 |
|
4 |
60.32 |
49.41 |
38.19 |
59.28 |
45.17 |
38.26 |
39.48 |
38.94 |
37.46 |
|
5 |
77.58 |
54.22 |
47.55 |
65.72 |
56.83 |
45.15 |
46.26 |
47.56 |
42.15 |
|
6 |
82.80 |
67.87 |
52.15 |
69.45 |
58.89 |
50.23 |
58.38 |
51.12 |
48.94 |
|
7 |
96.59 |
78.62 |
62.34 |
70.23 |
60.59 |
59.58 |
67.86 |
56.49 |
55.54 |
|
8 |
81.85 |
64.28 |
71.89 |
64.78 |
64.23 |
81.42 |
60.54 |
60.68 |
|
|
9 |
98.28 |
71.35 |
74.64 |
68.36 |
68.32 |
84.56 |
69.28 |
64.33 |
|
|
10 |
78.66 |
75.35 |
74.12 |
74.25 |
86.18 |
73.34 |
69.79 |
||
|
11 |
|
85.63 |
77.98 |
79.72 |
89.37 |
92.12 |
78.5 |
75.41 |
|
|
12 |
|
92.20 |
|
83.96 |
95.78 |
98.56 |
86.21 |
80.23 |
|
Fig 3: Dissolution profile of
Propranolol Hydrochloride (F1-F9 formulations)
From the
dissolution data it was evident that the formulations prepared with Locust bean
gum as polymer drug release was able to retard in lower concentration of
polymers. Polymer concentration increases the drug release up to desired time
period 12 hours.
Whereas the
formulations prepared with higher concentration of Kollidon SR retarded the
drug release up to 12 hours in the concentration 21mg. In lower concentrations
the polymer was unable to retard the drug release.
Whereas the
formulations prepared with Karaya gum were retarded the drug release in the
concentration of 7 mg (F7 Formulation) showed required release pattern i.e.,
retarded the drug release up to 12 hours and showed maximum of 98.56% in 12
hours with good retardation.
From the above results it was
evident that the formulation F7 is best formulation with desired drug release
pattern extended up to 12 hours.
Drug – Excipient compatability studies:
Fourier Transform-Infrared Spectroscopy:
Figure
4: FT-IR Spectrum of Propranolol Hydrochloride pure drug
Figure
5: FT-IR Spectrum of Optimised Formulation
From the FTIR data it was
evident that the drug and excipients doses not have any interactions. Hence
they were compatible.
CONCLUSION:
In the present work, an
attempt has been made to develop Controlled release tablets of Propranolol
Hydrochloride by selecting different Types of polymers Locates bean gum,
kollidon SR and Karaya gum as retarding. All the formulations were prepared by
direct compression method. From the FTIR data it was evident that the drug and
excipients doses not have any interactions. Hence, they were compatible. The
blend of all the formulations showed good flow properties such as angle of
repose, bulk density, tapped density. The prepared tablets were shown good post
compression parameters and they passed all the quality control evaluation
parameters as per I.P limits. Among all the formulations F7 formulation showed
maximum % drug release i.e., 98.56% in 12 hours. Hence it is considered
as optimized formulation F7 which contains karaya gum (7mg). Whereas the
formulations with HPMC showed high retarding with increasing concentration of
polymer. The formulations with Karaya gum were produced the desired drug
release pattern. The formulation F7 was followed Zero order release kinetics.
АCKNOWLEDGEMENT:
The Authors arе thankful
to Sura Labs, Dilshukhnagar, Hydеrabad for providing thе necessary
facilities for the research work.
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Received on 17.02.2020
Modified on 19.03.2020
Accepted on 08.04.2020 ©Asian Pharma Press
All Right Reserved
Asian J. Pharm. Res. 2020; 10(2):81-85.
DOI: 10.5958/2231-5691.2020.00015.5