Development and Evaluation of Propranolol Hydrochloride Floating Matrix Tablets Using Combination of Natural and Synthetic Polymers

Kasani Harikrishna Gouda*, V. Sai Kishore, N. Balaji, V. Vijaya Kumar and N. Raghuram

Department of Pharmaceutics, Bapatla College of Pharmacy, Bapatla, Guntur (Dt), Andhra Pradesh, India. 522101.

ABSTRACT:

In the present investigation, an attempt was made to formulate Propranolol hydrochloride sustained release floating matrix tablets using dried Hibiscus rosa-sinensis leaves mucilage and to study its release retardant activity in combination with hydroxypropyl methyl cellulose grades. Different floating matrix tablets of Propranolol HCl were formulated. The floating matrix tablets found to have better uniformity of weight, hardness, friability and drug content. The swelling behavior, release rate characteristics and the in- vitro dissolution study proved that the dried Hibiscus rosa-sinensis leaves mucilage can be used as a matrix forming material for preparing sustained release floating matrix tablets. The release rate followed zero-order release kinetics and the data was fitted in the Peppas plots. The exponential coefficient from the Peppas plots was found to be in between 0.55 to 0.64, indicating non-fickian mechanism of drug release.

KEYWORDS: Hibiscus rosa-sinensis leaves mucilage, Gastric residence time, Propranolol hydrochloride, Floating drug delivery, Hydroxypropyl methyl cellulose.

INTRODUCTION:

The oral route is considered as the most promising route of drug delivery. Effective oral drug delivery may depend upon the factors such as gastric emptying process, GI transit time, drug release from the dosage form and site of absorption. Gastric emptying of dosage forms is an extremely variable process, due to unpredictable gastric emptying rate and short gastric residence time. Gastric retention provides, longer residence time in the stomach that improves bioavailability for drugs that are readily absorbed upon release in the GI tract¹. These drugs can be delivered ideally by slow release from the stomach. Floating drug delivery, this system basically floats in the gastric fluid because of its lower density, than the gastric medium. Propranolol, a non-selective beta adrenergic blocking agent, has been widely used in the treatment of angina pectoris, hypertension, and many other cardiovascular disorders. It undergoes high first-pass metabolism by the liver, and on average, only about 25% of propranolol reaches the systemic circulation after oral administration. The t_1/2 of propranolol is 3-4 hrs.² Thus, propranolol has relatively short half-life. It also shows p^H dependent solubility; solubility at p^H 1.2 is 225 mg/ml, while at p^H 6.8 it is 130 mg/ml.

MATERIALS AND METHODS:

Materials:

Propranolol hydrochloride was obtained as gift sample from Natco Pharma Pvt. Ltd, Kothur and Hibiscus rosa-sinensis leaves were collected from local area, HPMC 50cps/K100M, magnesium stearate and talc were procured from SD Fine chemicals (Mumbai, India), microcrystalline cellulose and sodium bicarbonate were procured from Qualigens fine chemicals (Mumbai, India).

Methods:

Isolation of Hibiscus rosa-sinensis leaves mucilage:

The fresh leaves of Hibiscus rosa-sinensis Linn. were collected, washed with water to remove dirt and debris, and dried. The powdered leaves were soaked in water for 5 to 6 hrs, boiled for 30 mins, and kept aside for 1 hr for complete release of the mucilage into water. The material was squeezed from an eight-fold muslin cloth bag to remove the marc from the solution. Acetone was added to the filtrate to precipitate the mucilage in a quantity of three times the volume of the total filtrate. The mucilage was separated, dried in an oven at a temperature < 50 °C, collected, dried-powdered, passed through a sieve (number 80), and stored in airtight containers at room temperature³.

Preparation of Propranolol Hcl floating matrix tablets:

Propranolol hydrochloride floating matrix tablets were prepared by using different drug : polymer (Propranolol Hcl : HPMC 50cps + Hibiscus rosa-sinensis leaves mucilage) ratios viz. F₁ (1:1), F₂ (1:2), F₃ (1:4), F₄ (1:6), F₅ (1:8), F₆ (1:10) and drug : polymer (Propranolol Hcl : HPMC K100M + Hibiscus rosa-sinensis leaves mucilage) ratios viz. F₇ (1:1), F₈ (1:2), F₉ (1:4), F₁₀ (1:6), F₁₁(1:8), F₁₂(1:10). All the tablets were directly compressed in 16 station rotary tablet press. All the formulations contained 40 mg of Propranolol HCl, sodium bicarbonate (15%) as gas generating agent, microcrystalline cellulose as diluent, magnesium stearate (2%) as lubricant and talc (2%) added as glidant. The details of composition of each formulation are given in Table 1. The bulk powder was subjected to various micromeritic properties⁴.Values of angle of repose were found to be between 23.10º and 26.40º. The powder blend with Hausner ratio of 1.25 has good flow properties and the values were found to be between 1.08 and 1.21. These values showed that the powder blend had acceptable flow properties. The % compressibility was in the range of 16.24 and 18.74; the values between 12-20 have good compressibility which indicates that the powder blend is an acceptable range. All the formulations exhibited the desirable flow properties. The physicochemical properties of formulated floating matrix tablets viz., hardness, uniformity of weight and friability⁵ were within pharmacopoeial limits and these have uniformity of drug content¹. Also in-vitro buoyancy studies⁶ and matrix integrity were conducted, given in Table 2.

Swelling Index studies:

Swelling Index studies were conducted for the formulations F₄, F₅, F₆, F₁₀, F₁₁ and F₁₂ which passed the matrix integrity test. One tablet from each formulation was weighed individually (W₀) and placed separately in petridish containing 50 ml of 0.1N Hcl. The petridishes were placed in an incubator maintained at 37±0.5^oC. At regular 1 hr time intervals until 4 hrs, the tablets were removed from the petridish, reweighed (W_t), and the % swelling index⁷ was calculated using the following formula and the swelling behavior of floating matrix tablets were represented in fig. 1 and 2.

% W_U = (W_t-W_o/W_o) × 100

W_U – Water uptake, W_t – Weight of tablet at time t,

W_o – Weight of tablet before immersion.

Table 1: Composition of Propranolol HCl floating matrix tablets

Ingredients	F1	F2	F3	F4	F5	F6	F7	F8	F9	F10	F11	F12
Propranolol Hcl	40	40	40	40	40	40	40	40	40	40	40	40
HPMC 50 cps	20	20	20	20	20	20	--	--	--	--	--	--
HPMC K100M	--	--	--	--	--	--	20	20	20	20	20	20
Hibiscus rosa-sinensis leaves mucilage	20	60	140	220	300	380	20	60	140	220	300	380
Sodium bicarbonate (15%)	90	90	90	90	90	90	90	90	90	90	90	90
Microcrystalline cellulose	406	366	286	206	126	46	406	366	286	206	126	46
Magnesium stearate (2%)	12	12	12	12	12	12	12	12	12	12	12	12
Talc (2%)	12	12	12	12	12	12	12	12	12	12	12	12

*Total weight of tablet 600mg. All weights in milligrams; HPMC Hydroxypropyl methyl cellulose.

Table 2: Results of physical properties of Propranolol HCl floating matrix tablets

Formulation	Hardness (kg/ cm^2)	Weight variation(mg)	Friability (%)	Drug content(%)	Matrix integrity	Floating lag time (min)	Total floating time (hrs)
F1	3.7	598.64±0.37	0.73	100.46±0.4	-	-	-
F2	3.7	598.73±0.53	0.47	98.38±0.2	-	-	-
F3	3.9	599.85±0.14	0.36	99.84±0.7	-	-	-
F4	3.9	599.84±0.29	0.20	99.46±0.6	+	<2	<14
F5	4.1	598.37±0.35	0.63	98.47±0.5	+	<2	<!4
F6	4.6	599.85±0.24	0.48	99.86±0.5	+	<2	<14
F7	3.8	589.28±0.47	0.74	98.58±0.3	-	-	-
F8	4.1	599.19±0.77	0.27	100.84±0.6	-	-	-
F9	4.2	598.85±0.67	0.82	99.55±0.6	-	-	-
F10	4.2	589.94±0.86	0.84	99.48±0.3	+	<3	>14
F11	4.6	599.29±0.75	0.28	99.58±0.6	+	<3	>14
F12	4.8	599.85±0.57	0.47	99.65±0.2	+	<3	>14

Table 3: In vitro drug release kinetic data of Propranolol HCl floating matrix tablets

Formulation	Correlation coefficient				Release kinetics			Exponential coefficient (n)
	Zero order	First order	Higuchi	Peppas	K o (mg/hr)	t50 (hr)	t90 (hr)
F4	0.9599	0.9367	0.9842	0.9903	3.79	4.0	7.3	0.5744
F5	0.9635	0.9487	0.9787	0.9864	3.13	5.0	9.1	0.5556
F6	0.9721	0.8680	0.9751	0.9827	2.98	5.5	9.9	0.5831
F10	0.9690	0.9576	0.9807	0.9945	3.59	4.4	7.9	0.6337
F11	0.9717	0.9684	0.9653	0.9852	2.97	5.5	10.0	0.6076
F12	0.9836	0.8835	0.9675	0.9884	2.96	5.8	10.5	0.6472

Figure 1: Results of Swelling Index Studies of formulations F₄-F₆

Figure 2: Results of Swelling Index Studies of formulations F₁₀-F₁₂

In vitro dissolution studies:

The release of Propranolol hydrochloride from the tablet was studied using dissolution apparatus USP -Type II paddle apparatus. Drug release profile was carried out in 900 ml of 0.1N Hcl maintained at 37±0.5°C temperature at 100 rpm. 5 ml of samples were withdrawn at regular time intervals. The samples were replaced by its equivalent volume of dissolution medium and were filtered through 0.45 µm whatman filter paper and analyzed at 290 nm by UV spectrophotometer⁸. The in vitro dissolution rates were further tested using pharmacokinetic models. The amount of drug released vs. time (zero order release plot) was shown in fig. 3 and the in vitro drug release kinetic data was represented in Table 3.

Figure 3: Comparative Zero order plots of Propranolol Hcl floating matrix tablets

Figure 4: Comparative Peppas plots of Propranolol HCl floating matrix tablets

IR Spectral Analysis:

IR spectral analysis was used to study the interactions between the drug, polymer and the excipients⁹. The drug and excipients must be compatible with one another to produce a product stable, efficacious and safe. Based on the IR data, it was found that, there is no significant interaction between the drug and polymer as evidenced by the presence of bands due to the corresponding reactive functional groups. IR spectral analysis for pure drug and optimized formulation are shown in fig. 5 and 6 respectively.

Figure 5: Infrared spectrum of Propranolol HCl

Figure 6: Infrared spectrum of physical mixture of optimized formulation (F₁₂)

RESULTS AND DISCUSSION:

Floating matrix tablets, each containing 40 mg of Propranolol hydrochloride were prepared using dried mucilage of Hibiscus rosa-sinensis leaves in combination of hydroxypropyl methyl cellulose grades. The results shown that, as the proportion of Hibiscus rosa- sinensis leaves mucilage increased, the overall time for release of the drug from the floating matrix tablets was also increased. The release rate followed zero-order release kinetics and the data was fitted in the Peppas plots represented in fig. 4 and the mechanism of drug release followed non fickian mechanism of drug release. F₁₂ formulation was considered as optimized formulation, with drug release sustained for more than 12hrs than other formulations.

CONCLUSION:

The present investigation revealed that Hibiscus rosa-sinensis leaves mucilage appears to be suitable for use as a release retardant in the formulation of sustained release floating matrix tablets because of its good swelling, good flow and suitability for matrix formulations and further the drug release can be modified by using different hydroxypropyl methyl cellulose grades in combination with dried Hibiscus rosa-sinensis mucilage. From the dissolution study, it was concluded that dried Hibiscus rosa-sinensis mucilage can be used as an excipient for making sustained release floating matrix tablets of Propranolol hydrochloride.

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Received on 20.06.2011

Accepted on 04.08.2011

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Research Journal of Pharmaceutical Dosage Forms and Technology. 3(6): Nov.- Dec., 2011, 276-280