Formulation and Evaluation of Sustained Release Floating Matrix Tablets of Labetalol Hydrochloride.

 

Ravi K. Barde^1*, Minal R. Narkhede¹, V.R. Gudsoorkar², Rahul K. Amrutkar¹ and  Prashant S.Walke¹.

¹Department of Pharmaceutics, MGV’s College of Pharmacy, Panchavati, Nasik-422 003, India.

²Dept. of Pharmaceutics, N.D.M.V.P. Samaj’s College of Pharmacy, Gangapur Road, Nasik-422 002, India.

*Corresponding Author E-mail: barde_ravi@yahoo.com

ABSTRACT:

The present study was aimed at preparing a Floating matrix drug delivery system for the model drug Labetalol Hydrochloride, and evaluating the various processing parameters including the buoyancy studies and in vitro drug release studies. Floating matrix tablets of Labetalol hydrochloride were developed to prolong gastric residence time and increase its bioavailability. Floating matrix tablets containing 85 mg Labetalol Hydrochloride were developed using different polymer combinations. Seven formulations containing varying proportions of polymers like HPMC K4M and Carbopol 934 P, Sodium carboxy methyl cellulose and fixed amount of gas generating agent such as Sodium bi carbonate were prepared. The tablets were prepared by direct compression technique. The formulations were optimized on the basis of acceptable tablet properties, floating lag time, total duration of floating and in vitro drug release. The prepared tablets remained buoyant for 17 hrs in the release medium. The results of dissolution studies, floating lag time indicated that formulations S1 exhibited good and controlled drug release. Applying the linear regression analysis and model fitting showed the selected formulation S1 showed diffusion coupled with erosion drug release mechanism, followed zero order kinetics. Optimized floating matrix tablets S1 showed no change in physical appearance, drug content, or in vitro dissolution pattern after storage at 40°C / relative humidity 75% for a period of 3 months.

 

KEYWORDS: Floating matrix tablets, Buoyancy, Labetalol Hydrochloride, Total floating time (TFT), Floating lag time (FLT),

 

 

INTRODUCTION:

Most of the orally administered dosage forms have several physiological limitations, such as GI transit time, incomplete drug absorption due to incomplete release of drug from the devices and too short residence time of the dosage forms in the absorption region of GI tract. To overcome these limitations many attempts have been made by scientists by designing various drug delivery systems. Among these systems, floating drug delivery systems (FDDS) is one of the approaches which remain buoyant due to their lower density than that of the GI and intestinal fluids. Gastro retentive systems can remain in the gastric region for several hours and hence significantly prolong the gastric residence time of the drug.

 

Prolonged gastric retention improves bioavailability, reduces drug waste, and improves solubility for drugs that are less soluble in a high pH environment. It has applications also for local drug delivery to the stomach and proximal small intestines. Gastro retention helps to provide better availability of new products with new therapeutic possibilities and substantial benefits for patients¹.

 

Labetalol hydrochloride, 2-Hydroxy-5-[1-hydroxy-2-[(1-methyl-3-phenylpropyl) amino] ethyl]-benzamide, a non-selective α, β-adrenoceptor antagonist which is used in the treatment of hypertension. It is appreciably soluble in lower and higher pH solutions, with minimum solubility between pH 6 to 10. The drug shows variable bioavailability ranging from 10-80% which may be attributed to its instability in alkaline pH and poor absorption due to precipitation. It is administered in doses ranging from 50-200 mg twice a day due to its shorter half life of 3-6 hrs suggesting the need for sustained release formulation^{2, 3}.

 

 

The major objective of the present investigation was to develop a gastro retentive drug delivery system containing Labetalol Hydrochloride using simplex Centroid design as an optimization technique. The present study involved the design of Labetalol Hydrochloride gastric floating matrix tablets by combining three polymers: HPMC K4M, Carbopol 934P and Sodium carboxymethyl cellulose, and investigation of the combined effect of these polymers on the floating behavior and in vitro release pattern of the drug.

 

Floating drug delivery systems remain buoyant in the stomach for prolonged period of time without affecting the gastric emptying rate of other contents. Floating matrix systems containing HPMC as the matrix forming excipient begin to swell and form a gel layer with entrapped air around the tablet core after contact with gastric fluid, whereas this gel layer controls the drug release^{4, 5}. Another possibility for the induction of floatation lies in the incorporation of sodium bicarbonate, citric acid as gas forming agent dispersed in a HPMC hydrogel matrix as a method.

 

MATERIALS AND METHODS:

Materials:

Labetalol hydrochloride was obtained as a gift sample (Mercury Labs. Ltd, Baroda, Gujrat India).Hydroxypropyl methylcellulose K4M (HPMC K4M) and Carbopol 934 P were received as gift samples from the Watson Pharma Pvt. Ltd (India). All other ingredients used were of analytical grade and were used as received.

 

Methods:

Fabrication of Labetalol Hydrochloride floating tablets:

LBT Floating tablets were formulated as per the formulations given in Table 1. All the ingredients were weighed accurately. Drug was mixed with required quantity of all ingredients by geometric mixing. This blend was directly compressed into tablets using 10-mm flat-face round tooling on a rotary tablet machine. Compression force was adjusted to obtain tablets with hardness in range of 5 to 6 kg/cm². Tablets weighed 300 mg, and were round flat-face with an average diameter of 10 ± 0.1mm and thickness of 3.4 ± 0.2 mm. Formulations of the simplex centroid design batches (S1 to S7)⁶ are shown in Table 1.

 

Evaluation of Powder Blend of tablets ^{7, 8, 9}

The flow properties of powder blend were characterized in terms of angle of repose, Carr’s index and Hausner's ratio. The bulk density and tapped density were determined and from this data Carr's index and Hausner's ratio were calculated.

 

Angle of repose:

The angle of repose of powder blend was determined by the funnel method. The accurately weight powder blend were taken in the funnel. The height of the funnel was adjusted in such a way the tip of the funnel just touched the apex of the powder blend. The powder blend was allowed to flow through the funnel freely on to the surface. The diameter of the powder cone was measured and angle of repose was calculated using the following equation.

tan θ= h/r

Where, h and r are the height and radius of the powder cone.

 

Bulk density (BD):

Apparent bulk density was determined by pouring presieved drug excipient blend into a graduated cylinder and measuring the volume and weight “as it is”. It is expressed in g/ml and is given by

Db = M / V0

Where, M is the mass of powder and V0 is the Bulk volume of the powder.

 

Tapped density (TD):

It was determined by placing a graduated cylinder, containing a known mass of drug- excipient blend, on mechanical tapping apparatus. The tapped volume was measured by tapping the powder to constant volume. It is expressed in g/ml and is given by eq.

Dt = M / Vt

Where, M is the mass of powder and Vt is the tapped volume of the powder.

 

Compressibility Index:

Compressibility index of the powder blend was determined by Carr’s compressibility index. It is a simple test to evaluate the BD and TD of a powder and the rate at which it packed down. The formula for Carr’s index is as below:

Carr’s index (%) = [(TD-BD) ×100] / TD.

 

Hausner’s Ratio:

Hausner’s Ratio is a number that is correlated to the flow ability of a powder.

Husner’s Ratio = TD / BD

 

Evaluation of prepared tablets ^{8, 10, 11, 12, 13, 14, 15}

The prepared Labetalol hydrochloride floating tablets were evaluated for thickness, hardness, friability, uniformity of weight and drug content.

 

Thickness:

The thickness of tablet was determined using Vernier caliper. Six tablets from each batch of formulation were used and mean thickness value and standard deviation were calculated for each formulation.

 

Hardness:

For each formulation, the hardness of six tablets was measured using the Monsanto hardness tester and mean value and standard deviation was calculated.

 

Weight variation:

To study the weight variation, 20 tablets of each formulation were weighed using an electronic digital balance. The average weight of each tablet was calculated and the percentage deviation in weight was calculated.

Table no 1: Composition of Labetalol hydrochloride floating tablets.

Ingredients (%)	S1	S2	S3	S4	S5	S6	S7
Labetalol Hydrochloride	28.33	28.33	28.33	28.33	28.33	28.33	28.33
HPMC K4M	26.66	13.33	13.33	13.33	13.33	13.33	8.88
Carbopol 934 P	10	23.33	10	11.66	11.66	10	7.77
Sodium CMC	5	5	15	5	7.5	7.5	5
Sodium bicarbonate	16.66	16.66	16.66	16.66	16.66	16.66	16.66
Citric acid	8.33	8.33	8.33	8.33	8.33	8.33	8.33
Magnesium stearate	1.66	1.66	1.66	1.66	1.66	1.66	1.66
Talc	1.66	1.66	1.66	1.66	1.66	1.66	1.66
Lactose	Q.S	Q.S	Q.S	Q.S	Q.S	Q.S	Q.S

HPMC- Hydroxypropyl methyl cellulose, Sodium CMC- Sodium carboxy methyl cellulose. Average weight of each tablet was made to 300 mg with Lactose.

 

 

Table 2: Evaluation of powder blend.

Formulation code	Angle of repose (θ)	Bulk density (gm/ml)	Tapped density (gm/ml)	Compressibility index (%)	Hausner’s Ratio
S1	34.56±0.022	0.283 ±0.0043	0.332±0.0042	15.66±2.65	1.18
S2	40.39±0.056	0.231 ±0.0041	0.271±0.0026	14.44±1.82	1.16
S3	39.21±0.046	0.206±0.0032	0.274±0.0028	23.70±3.87	1.31
S4	39.69±0.047	0.210±0.0035	0.270±0.004	22.22±2.71	1.28
S5	40.99±0.051	0.245±0.0037	0.282±0.0038	13.12±1.32	1.15
S6	37.56±0.030	0.211±0.0024	0.250±0.0051	15.61±2.75	1.18
S7	40.39±0.053	0.204±0.0026	0.282±0.0024	27.65±2.04	1.38

 

 

Friability Test:

The friability of tablets were determined using Roche Friabilator. It is expressed in percentage (%). Ten tablets were initially weighed (W_initial) and transferred into friabilator. The friabilator was operated at 25rpm for 4 minutes or run up to 100 revolutions. The tablets were weighed again (W_final). The % friability was then calculated by –

% Friability = 100 (1-W_initial/ W_final)

% Friability of tablets less than 1% are considered acceptable.

 

Drug content:

Ten tablets were weighed individually and powdered. The powder equivalent to average weight of tablets was weighed and drug was extracted in 0.1 N HCl, the drug content was determined measuring the absorbance at 302 nm after suitable dilution using a Shimadzu UV/Vis double beam spectrophotometer.

 

In -Vitro Buoyancy Study:

The in-vitro buoyancy study was characterized by floating lag time and total floating time. The time taken for tablet to emerge on the surface of the medium is called the floating lag time (FLT) or buoyancy lag time (BLT) and duration of time the dosage form constantly remains on the surface of the medium is called the total floating time (TFT). The test was performed using a USP type II paddle apparatus using 900 ml of 0.1 N HCl at paddle rotation of 50 rpm at 37 ± 0.5°C. The time of duration of floatation was observed visually.

 

Swelling Characteristics (Water Uptake Study):

The swelling properties of HPMC matrices containing drug were determined by placing the tablet matrices in the dissolution test apparatus, in 900 ml of 0.1 N HCl at 0 37± 0.5°C. The tablets were removed periodically from dissolution medium. After draining free from water by blotting paper, these were measured for weight gain. Swelling characteristics were expressed in terms of percentage water uptake (WU %) show relationship between swelling index and time.

 

               Weight of swollen tablet – Initial weight of the tablet

WU % = --------------------------------------------------------- x 100

                                  Initial weight of the tablet

 

In Vitro Dissolution Studies:

The release rate of Labetalol hydrochloride floating tablets were determined by using Dissolution testing apparatus USP type II (Paddle type). The dissolution testing was performed using 900ml of 0.1N HCl at 37± 0.5° C temperature and speed 100 rpm. A sample (5ml) of the solution was withdrawn from the dissolution testing apparatus hourly for 12 hours and the samples were replaced with fresh dissolution medium. The samples were filtered through a 0.45μ membrane filter and diluted to a suitable concentration with 0.1N HCl. Absorbance of these solutions was measured at 302 nm wavelength using a Shimadzu UV/vis double-beam spectrophotometer. Analysis of data was done by using 'PCP Disso V-3' software, India.

 

Kinetic modeling and mechanism of the in vitro release:

Data obtained from in vitro release studies was fitted to various kinetic equations to find out the mechanism of drug release from sustained release floating matrix tablets. The kinetic models used were zero order, first order, Higuchi model, and Koresymer and Peppas model to further characterize the type of release.

 

Table 3: Evaluation of tablet batches.

Formulation code	Hardness (kg/cm2)	Friability	Uniformity of weight (mg)	Thickness (mm)	Drug content (%)
S1	4.83±0.59	0.9559±0.06	295.85±3.47	3.96±0.33	96.901±0.68
S2	4.76±0.42	0.9870±0.03	291.62±2.67	3.24±0.30	95.022±0.74
S3	4.28±0.23	0.5751±0.06	295.3±3.15	3.22±0.28	90.659±0.47
S4	4.58±0.69	0.9760±0.02	297.03±2.45	3.14±0.21	91.386±0.87
S5	4.36±0.71	0.8764±0.02	291.07±2.55	3.16±0.18	96.159±0.53
S6	4.44±0.21	0.579±0.04	298.46±2.79	3.22±0.19	92.977±0.84
S7	4.79±0.32	0.688±0.01	294.25±3.13	3.08±0.21	94.046±0.71

 

 

The drug release data were evaluated by the model-dependent (curve fitting) method. In the present study, the Korsmeyer-Peppas model describing drug release from polymeric system was used. This model takes into account that the drug release mechanism often deviates from the Fick’s law and follows anomalous behavior described by the following equation:

Mt/M∞ = k. tn

 

Where, Mt is the drug released at time t, M∞ the quantity of drug released at infinite time, k the kinetic constant and n is the release exponent. The value of n is related to the geometrical shape of the delivery systems and determines the release mechanism.

 

The value of n in equation determines the mechanism of drug release. When n approximates to 0.5, a Fickian/diffusion controlled release is implied, where 0.5<n<1.0 non- Fickian transport and for n=1 zero order (case II transport). When n approaches 1.0, one may conclude that the release is approaching zero order.

 

Stability study:

Gastro retentive tablets of Labetalol hydrochloride formulated in the present study were subjected to short term accelerated stability studies. Stability studies of the prepared formulations were performed at 40^oC with 75% RH for a period up to three months. At every one month intervals the tablets was evaluated for all physical parameter.

 

RESULTS AND DISCUSSION:

Labetalol hydrochloride with all available information proved to be a suitable candidate for development of sustained release formulation. The present investigation was to fabricate and evaluate the sustain release formulation Labetalol hydrochloride floating matrix tablet. The tablets were prepared by using combined polymers i.e. HPMC K4M, Carbopol 934, and Sodium CMC by direct compression technique. In each batches 30 tablets were prepared. Before compression the formulated blend was subjected for various evaluation parameters. The powder blend was evaluated by the measurement of bulk density, tapped density, angle of repose, compressibility index and hausner’s ratio. The formulations showed good flow property and compressibility index (Table 2). Angle of repose ranged from 34.56 to 40.39 and the compressibility index ranged from 13.12 to 27.65. The Bulk density and Tapped density of the powder blend ranged from 0.204 to 0.283 and 0.250 to 0.332 respectively. Hausner’s ratio range from 1.16 to 1.38. The results of angle of repose indicates poor flow property of the powder blend and the value of compressibility index and Hausner’s ratio further showed support for the flow property.

 

Tablets of different formulations were subjected to various evaluation tests, such as thickness, uniformity of weight, drug content, hardness, friability, and in vitro dissolution.  The shape of the tablets of all formulations remained circular with no visible cracks. All formulations showed uniform thickness. The thickness ranged from 3.08 mm to 3.96 mm.

 

Average percentage deviation of all tablet formulations was found to be within the limit, and hence all formulations passed the test for uniformity of weight as per official requirements. Good uniformity in drug content was found among different batches of tablets and percentage of drug content was more than 90%.The hardness of all tablet formulation was in the range of 4 to 5 kg/cm².Tablet hardness is not an absolute indicator of strength. Another measure of a tablet’s strength is friability. Conventional compressed tablets that lose less than 1% of their weight are generally considered acceptable. In the present study, percentage friability for all formulations was below 1%, indicating that friability was within the prescribed limits. (Table 3).

 

All the formulations showed values within the prescribed limits for tests like hardness, friability and weight variation which indicate that the prepared tablets are of standard quality.

 

In all Tablets batches (S1 to S7) floating lag time variation from 32 sec to 69 sec was observed. All tablet formulations exhibited satisfactory floatation ability and remained buoyant for more than 15 h in dissolution medium. Formulation S2 containing highest amount of Carbopol 934P has longer floating lag time (Table 4 shows the results of buoyancy study) (Fig.1).

 

The pH of stomach is elevated under fed condition (~3.5). In this pH condition the buoyancy lag time increases or sometimes the tablet can’t float, so to make the tablet buoyant citric acid was added in the formulation to provide an acidic medium to Sodium bicarbonate. The combination of sodium bicarbonate and citric acid thus provided desired floating ability. It was observed that the gas generated is trapped and protected within the gel, formed by hydration of polymer (Hydroxy Propyl Methyl Cellulose and Carbopol 934), thus decreasing the density of the tablet below 1 and tablet becomes buoyant.

 

As the amount of HPMC K4M and sodium carboxy methyl cellulose increased, TFT increased; this is because of increased gel strength of matrices due to hydrophilic nature of polymers which produces easy swelling of tablets, which prevents escape of evolved carbon dioxide from matrices, leading to decreased density. As the amount of Carbopol 934 P increased, TFT decreased this may be due to high affinity of carbopol towards water, which promotes water penetration into tablet matrices, leading to increased density.

 

Initial Time.

 

Time 19 Sec.

 

Time 32.68 Sec.

Figure1: Floating Lag Time of Labetalol HCL Floating Matrix Tablet-S1.

 

Table 4: In vitro buoyancy studies.

Formulation code	Floating lag time  (sec)	Total Floating time (hr)
S1	32.68	15
S2	69.42	10
S3	42.52	17
S4	65.14	17
S5	47.15	17
S6	53.45	17
S7	40.67	14

 

Swelling characteristics:

The effect of HPMC K4 M, Carbopol 934 P and SCMC on swelling index was found to be highly significant. The percentage water uptake of the formulations (S1–S7) at 12 hr ranged from 141.66 to 173 %, (Figure 2 shows the results of swelling studies). Because of hydrophilic nature of the polymers the percentage water uptake was found to be increased on increasing the concentration of these polymers in the formulations and, hence, the water uptake capacity increases. Drug diffusion depends significantly on the water content of the tablet. This may be because the mobility of the polymer chains is very dependent on the water content of the system. In the case of high water content, polymer chain relaxation takes place with volume expansion resulting in marked swelling of the system.

 

Figure 2: Swelling indices of formulations.

Table 5: Percent drug release data.

Sr. No	% Drug released	S1	S2	S3	S4	S5	S6	S7
1	1 Hr	6.54±0.30	11.16±0.31	8.34±0.46	9.04±0.53	7.31±0.81	9.33±0.45	11.93±0.46
2	2 Hr	10.23±0.13	17.90±0.71	11.35±0.27	12.41±0.51	14.92±0.77	12.51±0.31	18.38±0.06
3	3 Hr	14.32±0.34	21.27±0.17	16.94±0.32	17.80±0.34	17.67±0.48	15.11±0.28	20.09±0.04
4	4 Hr	17.32±0.27	24.64±0.39	19.05±0.19	22.71±0.72	22.91±0.37	19.15±0.44	30.22±0.89
5	5 Hr	20.21±0.69	33.49±0.17	21.17±0.37	23.48±0.34	24.35±0.84	22.14±0.23	41.48±0.93
6	6 Hr	27.91±0.15	36.67±0.29	28.68±0.54	31.48±0.6	34.46±0.44	26.37±0.47	47.26±0.44
7	7 Hr	30.51±0.22	45.43±0.32	35.42±0.47	38.11±0.3	37.92±0.69	29.07±0.44	50.15±0.49
8	8 Hr	46.59±0.43	50.15±0.48	39.94±0.16	44.08±0.16	39.75±0.48	35.32±0.57	53.81±0.84
9	9 Hr	57.56±0.38	56.98±0.31	66.13±0.43	49.95±0.32	46.87±0.36	37.83±0.68	57.08±0.72
10	10 Hr	66.22±0.42	62.08±0.41	69.30±0.22	53.81±0.14	51±0.40	40.91±0.43	59.77±0.48
11	11 Hr	86.16±0.21	75.75±0.27	75.85±0.61	59±0.34	56.69±0.32	44.18±0.38	66.70±0.57
12	12 Hr	91.34±0.38	78.45±0.26	77.87±0.51	65.3±0.44	60.74±0.63	50.15±0.61	70.36±0.51

*Each sample was analyzed in triplicate (n = 3)

 

Table No. 6: Kinetic treatment to dissolution data for floating matrix tablet formulations

Formulations	Zero order Plot	First order Plot	Korsmeyer- Peppas Plot	Matrix Plot	Hix. Crow Plot	Best fit Model.
	Regression Coefficient (R2)	Regression Coefficient (R2)	Regression Coefficient (R2)	Regression Coefficient (R2)	Regression Coefficient (R2)
S1	0.9566	0.9321	0.9614	0.8297	0.8509	Peppas
S2	0.9926	0.9119	0.9846	0.9341	0.9184	Peppas
S3	0.9706	0.9038	0.9812	0.8609	0.8402	Peppas
S4	0.9956	0.9219	0.9902	0.9114	0.8349	Peppas
S5	0.9967	0.9143	0.9898	0.9262	0.8193	Peppas
S6	0.9960	0.9420	0.9974	0.9447	0.9768	Peppas
S7	0.9890	0.9524	0.9944	0.9943	0.9290	Peppas

 

Dissolution study:

The dissolution rate studies were performed to evaluate the dissolution character of Labetalol hydrochloride from the floating tablets. Table 5 shows the percent drug release data of all the developed formulations.

 

The dissolution study of all formulations shows the percentage drug release were found to be S1-91.34%, S2- 78.45%, S3-77.87%, S4-65.36%, S5-60.74%, S6-50.15% and S7-70.36% in 12hour period. From all the formulations S1 showed faster drug release and S6 showed slow drug release when compared to other formulations. Hence S1 was considered to be the best formulation based on its release characteristics. Figure 3 shows release profile of all the seven batches.

 

Figure 3: Comparative in vitro release profile of all seven batches.

 

Kinetics of drug release:

The dissolution data of batches S1 to S7 was fitted to Zero order, First order, Higuchi and Korsmeyer-Peppas models (Table 6). The coefficient of determination (R²) value was used as criteria to choose the best model to describe drug release from the tablets. The R² values of various models are given in Table. In case of all the formulations the R² values were higher for Zero order model than for First order model indicating that the drug release from the formulation followed Zero order kinetics.

 

The value of release exponent “n” obtained from Krosmeyer equation was greater than 0.5 for all the formulations. The values of ‘n’ in Peppas model also indicated that all the formulations followed diffusion and anomalous release; this indicated that the drug released is controlled by both diffusion and erosion.

 

Formulations S1, S2, S3, S4, S5, S6 exhibited anomalous (non Fickian transport) diffusion/polymer relaxation mechanism with a n value ranging from 0.59 to 0.78. Whereas in case of formulations S7 exhibited zero-order release profile as their ‘n’ values were very close to 0.88. The results for  formulation S1 with n value of 0.8776 confirmed that the formulation followed zero order kinetics indicating Labetalol hydrochloride release from controlled drug delivery system were by both diffusion and erosion mechanism.

 

Stability study:

At the time of stability studies, the tablet of the best formulation S1 was subjected to evaluate for the Physico-chemical parameters, for every one month intervals up to three month. The results showed that there was no change in the physico-chemical properties of the tablets for the best S1. No visible changes in the appearance of the controlled release tablets were observed at the end of the storage period and there was no change in the drug content (Table 7).

Table 7: Stability studies of Labetalol HCL floating matrix tablets.

Sr. No	Parameters	After one month Observations	After two month Observations	After three month Observations
1	Physical Appearance	No change	No change	No change
2	Weight Variation (mg )	295.16 ± 3.0	295.18 ±2.9	295.18 ±3.2
3	Thickness (mm)	3.95 ±0.057	3.96 ±0.06	3.95± 0.02
4	Hardness (Kg/cm2)	4.81± 0.09	4.85± 0.2	4.83± 0.2
5	Friability (% )	0.95 ±0.03	0.93± 0.05	0.94 ±0.04
6	Drug Content (mg/tab )	96.35 ±0.37	96.55 ±0.28	96.53 ±0.23
7	Buoyancy lag time (Sec)	32.34± 0.2	32.45 ±0.1	32.51 ±0.17
8	Duration of Buoyancy (Hours)	>15	>15	>15

*All values are expressed as mean ± standard deviation, n =5

 

 

CONCLUSION:

The effervescent based floating drug delivery was a promising approach to achieve in vitro buoyancy. The addition of gel forming polymer (HPMC K4M) and gas generating agent sodium bicarbonate and citric acid were essential to achieve the in-vitro buoyancy. The drug release form the tablets were sufficiently sustained due to the presence of polymers. Labetalol hydrochloride floating tablet drug delivery system showed improved in-vitro bioavailability and extended drug release which may favour the reduced dose frequency and patient compliance.

From the results obtained, it was concluded that the formulation S1 is the best formulations as the extent of drug release was found to be around 91%. This batch also showed immediate floatation and floatation duration of more than 18hr. The drug release model of this formulation complies with zero order kinetics. Based on the results we can certainly say that floating type gastro retentive drug delivery system holds a lot of potential for drug having solubility as well as stability problem in alkaline pH or which mainly absorb in acidic pH. We can certainly explore this drug delivery which may lead to improved bioavailability and ensured therapy with many existing drugs. It is the responsibility of future scientists working in this area to effectively use the potential of this drug delivery system for the benefit of mankind.

 

ACKNOWLEDGMENT:

The authors are grateful to Mahatma Gandhi Vidyamandir’s College of Pharmacy, Nasik, for providing essential laboratory conditions for present research work. Also an author acknowledges to Mercury labs Pvt. Ltd (Baroda, India), for providing gift sample of Labetalol HCL.

 

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Received on 31.07.2011          Modified on 23.08.2011

Accepted on 04.09.2011         © RJPT All right reserved