Formulation and Evaluation of Propranolol HCl Floating Tablets- A Gastro Retentive Drug Delivery

 

Kabita Banik*, Dr. Y Phalguna, B Sangeetha

Bharat Institute of Technology, (BIT) Manganpally, Hyderabad, India.

 

ABSTRACT:

The objective of present study was to develop a gastroretentive drug delivery system of propranolol hydrochloride. The biggest problem in oral drug delivery is low and erratic drug bioavailability. This study” shown the formulation of floating tablets of Propranolol HCl by employing carbopol and HPMC as polymers. One of the disadvantages in using propranolol is extensive first pass metabolism of drug and only 25% reaches systemic circulation. The bioavailability of propranolol increases in presence of food. Also, the absorption of various drugs such as propranolol through P-glycoprotein (P-gp) efflux transporter is low and erratic. The density of P-gp increases toward the distal part of the gastrointestinal tract (GIT). Therefore, it was decided to formulate floating tablet of propranolol so that it remains in the upper part of GIT for longer time. The prepared tablets were evaluated among all the formulations (P1-P5). Formulations were evaluated for floating lag time, duration of floating, dimensional stability, drug content and in vitro drug release profile. It was observed that formulation”-5 has shown better buoyancy and dissolution profile.

 

 

 

INTRODUCTION:

Gastric emptying of dosage forms is an extremely variable process. Short and variable gastric emptying time can result in incomplete drug release from the delivery system above the absorption zone (stomach or upper part of small intestine), leading to diminished efficacy of the administered dose. Gastric retention provides advantages such as the delivery of drugs with narrow absorption windows in the small intestinal region. In addition, longer residence time in the stomach could be advantageous for local action in the upper part of the small intestine, for example treatment of peptic ulcer disease. Furthermore, improved bioavailability is expected for drugs that are readily absorbed upon release in the GI tract.

 

These drugs can be delivered ideally by slow release from the stomach. Various approaches are available for prolonging the residence time of drugs in the GI tract; among which floating drug delivery has drawn considerable attention. The system basically floats in the gastric fluid because of its lower density compared to that of the aqueous medium. Floating oral delivery systems are expected to remain buoyant in a lasting way upon the gastric contents and consequently to enhance the bioavailability of drugs. The lasting intragastric buoyancy of a controlled release dosage form might also provide a suitable manner to constantly deliver a drug locally into the stomach and hence achieve a sustained site-specific therapeutic action. Propranolol is a nonselective beta-adrenergic receptor blocking agent possessing no other autonomic nervous system activity. It is used as antihypertensive, antianginal, antiarrhythmic, and in treatment of migraine. Propranolol is reported to be of value in more than 20 non cardiovascular disorders, many of which are associated with central nervous system. Propranolol has short half-life, high first-pass metabolism, presence of food increases the bioavailability, P-gp plays important role in the absorption, and the drug is acid-soluble basic drug which make it suitable for GRDDS.

 

MATERIALS AND METHODS:

Materials:

Propranolol hydrochloride was obtained as gift sample from Raks Pharmaceuticals, Vizag. HPMC K15M, Carbopol 940, MCC, Sodium bi carbonate, Magnesium stearate, Talc (Bharat Institute of Technology, Hyderabad, India). All the chemicals used were reagent grade.

 

Instruments Used:

Tablet Compression Machine, Pfizer Hardness Tester, Usp Dissolution Apparatus, UV-Vis Double Beam Spectrophotometer. 

 

METHODS:

Pre formulation parameters:

The _ properties _ like _ compressibility _ index, _ angle of _ repose _ and _ Hausner _ ratio _ were _ calculated” for the active pharmaceutical ingredients.

 

Formulation Procedures:

Drug and polymers pass through 40 # mesh separately and then transfer it to poly bag and mix it for 3 minutes. Add diluents and other excipients to the above mixture. Finally add the glidant (Magnesium Stearate) and Lubricant (Talc) to the above blend mix it for 2min. Compressed the above lubricated blend by using 8mm round punches.

 

Evaluation of powder blend:

The powder blend was evaluated for flow properties. Different tests that were carried out are angle of repose, loose bulk density, tapped bulk density, and compressibility index, and Hausner ratio was calculated.

 

Evaluation of matrix tablets:

Tablets were subjected to various tests like hardness, friability, uniformity of drug content, and uniformity of mass of single dose preparation as per US Pharmacopeia (USP).

 

Buoyancy lag time/lag time for floating of tablets:

Buoyancy lag time test was performed to check the floating behavior. The tablets were dropped in the dissolution medium, i.e., 0.1 N HCl and the time taken by them to come to the surface of the dissolution medium, i.e., time taken for floating on surface was reported.

 

In vitro drug release for all test formulations:

The in vitro drug release was studied by conducting dissolution test for tablets. Dissolution was carried out using USP XIII dissolution apparatus type II (paddle type). Nine hundred milliliters of 0.1 N HCl, which was maintained at 37°C, was used as dissolution medium. The speed of paddle was maintained at 50 rpm. Five milliliters samples were withdrawn at the time intervals of 10, 30, _60, _ 120, _ 240, _ 360, _ and _ 600min and replaced with equal volume of fresh dissolution medium maintained at same temperature. The samples were filtered and suitably diluted. Absorbances of these solutions were recorded at wavelength 211 nm using UV spectrophotometer. All the studies were carried out in triplicate.

 

RESULTS AND DISCURSION:

Formulation Design of Propranolol Hcl Floating Tablets:

 

Table 1:Composition of propranolol hcl floating tablets

Ingredients	Formulations
	P1	P2	P3	P4	P5
Propranolol_ hcl	50	50	50	50	50
HPMCK15M(mg)	100	---	50	60	60
Carbopol_ 940(mg)	---	100	50	40	40
MCC	52	52	52	52	52
Sodium bi carbonate (mg)	35	35	35	35	35
Magnesium stearate (mg)	2	2	2	2	2
Talc (mg)	1	1	1	1	1
Total wt (mg)	240	240	240	240	240

 

Pre formulation Study:

Micro meritic properties of Active Pharmaceutical Ingredient:

 

Table 2: Micro meritic properties of Active Pharmaceutical Ingrediens

Parameter	Results
Angle of repose	26.45±0.1
Bulk Density	0.95±0.3gm/ml
Tapped Density	1.02±0.2gm/ml
Compressibility Index	7.36±0.5%
Hausner’s ratio	1.07±0.29

 

All the values are within the limit so our API Propranolol passes the pre formulation test.

 

Evaluation of powder blend

Table 3:Evaluation of tablet blend

Parameter	P1”	P2”	P3”	P4”	P5”
Angle of_ repose	25.43±0.1_	26.46±0.2	23.31±0.17	27.29±0.17	29.14±0.13
Bulk_ density	0.725±0.3_	0.734±0.4	0.717±0.22	0.724±0.28	0.96±0.24_
Tapped_ density	0.829±0.18	0.854±0.23	0.832±0.16	0.843±0.21	1.03±0.27_
%Compressibility	12.54	14.05	13.82	13.63	7.29
Hausner’s_ ratio	1.14	1.16	1.16	1.16	1.07

 

Calibration of Standard curve of Propranolol HCL:

Standard graph of Propranolol hcl in 0.1 N HCl at λmax= 211.5nm.

 

Table 4: Standard graph of Propranolol hcl

CONCENTRATION (μg/ml)	ABSORBANCE
0	0
2	0.215
4	0.396
6	0.595
8	0.773
10	0.987

 

Figure 1: Standard graph of Propranolol hcl

 

Evaluation of the Prepared Tablets for Physical Parameters:

Table 5: Evaluation of Physical parameter.

Parameter	P1	P2	P3	P4	P5
Weight variation	260.9±2	260.1±2	260.8±2	260.7±2	260.1±2
Thickness(mm)	5.5±0.4	5.9±0.4	5.3±0.4	5.6±0.4	5.5±0.4
Hardness (kg/cm2)	8.9±1.4	7.4±1.2	8.2±1.2	6.9±0.9	8.4±1.9
Friability	0.12%±0.2	0.16%±0.2	0.15%±0.2	0.15%±0.2	0.15%±0.2
Content uniformity	95.01%±0.2	96.4%±0.4	98.7%±0.3	98.8%±0.2	99.8%±0.3
Floating lag time (min)	15	12	13	11	<1

 

Weight variations of all tablets in formulation P1-P5 were within the permeable limit (max different allow as per USP is 7.5% ).Thickness of all formulation was within the limit (5-6mm).Hardness of all tablets were compatible with USP process( limit 5.2-8.5 kg/cm2).In Friability test weight variation for all formulation are less than 1%. Content uniformity for all formulations was into the limit. The_ floating_ lag_ time was <1for P5. In the basis of The_ floating lag time P5 was established as the optimized formula.

 

Figure 2: Floating Lag time test for P5 formula.

In vitro Dissolution studies:

Dissolution profile for P1-P5:

 

Table 6: Results of % drug release profile for P1-P5.

% Drug Release
Time	P1	P2	P3	P4	P5
0	0	0	0	0	0
30	12.45	21.36	14.67	15.67	18.95
60	27.94	34.92	26.91	23.68	35.78
120	54.68	67.93	51.24	56.98	46.48
240	74.98	84.72	73.97	79.97	73.18
360	96.59	95.92	89.92	92.15	82.94
600	98.95	97.83	99.13	98.99	94.56

 

All the formula shows 12-18 % drug release at time 0-30min. 23-35% release at 60min. 45-67% release at 120min.73-74% release at 240min. 82-96% release at 360min and 94-99% release at 600min.

 

The % of drug release rate is decrease in the formulation P5. After 10hr 94% drug release in 0.1N HCl which was equivalent to the drug release in stomach.

 

Figure 3: % Cumulative drug release of P1-P5

 

CONCLUSION:

The objective of the present study is to develop a Floating bioadhesive tablets of Propranolol hcl has been fulfill. Among all the formulations (P1-P5), it was observed that formulation-5 has shown better buoyancy and dissolution profile. Formulation-5 was found to be the best formulation among others.

 

CONFLICT OF INTEREST:

This artical has not published before and it is not under consideration for publication in any other journal.

 

ACKNOWLEDGEMENT:

The Authors are thankful to the management authoritarians of BIT, Hyderabad for providing necessary facilities to carry out this study.

 

REFFERENCE:

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Received on 17.06.2019         Modified on 18.07.2019

Accepted on 16.08.2019       ©A&V Publications All right reserved