Formulation and Evaluation of Gastroretentive Floating Tablets of Febuxostat

 

Sanjesh Rathi*, Sohansinh Vaghela, Raj Shah, Shrenik Shah

Department of Pharmaceutics, Saraswati Institute of Pharmaceutical Sciences and Research,

Dhanap, Gujarat 382355.

 

ABSTRACT:

The present research work done with an objective of preparation and evaluation of floating tablets of Febuxostat drug with Hydroxypropylenemethyl cellulose (HPMC), Polyox N-60K, Carbopol 934 P and Guar gum polymers. Floating tablets were based on effervescent approach using sodium bicarbonate a gas releasing agent. Direct compression method was used in present study for preparation of tablets. Effect of polymers was evaluated by studying drug release and floating time. In-vitro drug release profile indicates that sustained nature increased by increasing the concentration of polymer. The formulation containing Polyox N-60K and Carbopol 934 P in combination was optimized as it showed drug release up to 12hrs. Optimized formulation F18 was found stable during stability condition up to 1 month.

 

 

 

1. INTRODUCTION:

Oral route of administration is the most important and convenient route for drug delivery. Due to differential absorption from various regions of GI, the benefits of long-term delivery Technology have not been fully realized for dosage forms designed for oral administration. Only recently drug delivery systems have been designed to target drugs to differential regions of GIT. These include gastro retentive systems, delayed release systems and colon targeting^.1 Gout is a common and complex form of arthritis that can affect anyone. It's characterized by sudden, severe attacks of pain, swelling, redness and tenderness in the joints, often the joint at the base of the big toe. An attack of gout can occur suddenly, often waking you up in the middle of the night with the sensation that your big toe is on fire. The affected joint is hot, swollen and so tender that even the weight of the sheet on it may seem intolerable. Gout symptoms may come and go, but there are ways to manage symptoms and prevent flares.²

 

2. MATERIALS AND METHODS:

Febuxostat received as gift sample from Astron research Ltd, Ahmedabad, Lactose DCL 11 used as diluents and HPMC K4M, Guar Gum, HPMC K100M, Carbopol 934, Polyox N-60K purchased from SD Fine Chemicals Ltd, Mumbai, India

 

Pre-Formulation Studies:

Characterization of API, Organoleptic Characteristics:

Colour, odour and Appearance of Febuxostat were characterized and recorded using descriptive terminology.

 

Flow Properties:

Bulk density and tapped density, Compressibility index (CI) / Carr’s index,  Hausner ratio Angle of repose , Drug Identification and Drug-Excipients interaction study by FTIR , DSC Study , Determination of λmax and Calibration Curve of Febuxostat , Calibration Curve of Febuxostat

 

Preparation of Floating Tablets of Febuxostat:

Dose Calculation for Sustained Release dosage form:

The total dose of Febuxostat for a sustained release formulation was calculated by following four equations using available pharmacokinetic data from a design of one compartment model with simultaneous release of loading dose and a zero order release maintenance dose, as described by Robison and Eriksen.^3,4

 

k0 = Dike (1)

Dm = k0T (2)

Dl = Di-k0Tp (3)

Dt = Dl + Dm (4)

 

Where, k0 = zero order drug release;

ke = 0.693/t_1/2; Di = initial dose/conventional dose; Dl = loading dose; Dm = maintenance dose; T = time for sustained action; Tp = time to reach peak plasma concentration; Dt = total dose of drug.

k0 = Dike = 40 × 0.693/5 = 5.544 mg (5)

Dm = k0T = 5.544 × 12 = 66.528mg (6)

Dl = Di-k0Tp = 40- (5.544 × 1.5) = 31.684 mg (7)

Dt = Dl + Dm = 31.684 + 66.528=98 mg (8)

 

Hence the tablet should contain a total dose of 98 mg for 12 h. sustained release dosage form and it should release 31 mg in 1st hour like conventional dosage form and remaining dose (67 mg)in remaining 11 hours, Hence, the theoretical drug release profile can be generated using above value, which is shown in below table1.

 

Table 1: Theoretical drug release profile

Time in hour	mg of drug	% of Drug
1	31	32
2	37	38
3	43	44
4	49	50
5	55	57
6	62	63
7	68	69
8	74	75
9	80	81
10	86	88
11	92	94
12	98	100

 

Method of Preparation:

·       Febuxostat Floating tablets were prepared by direct compression method.

·       Weigh all the materials as per formula sheet and pass through #40 mess sieve.

·       Mix all ingredients by geometric manner and prepare a blend.

·       Check the pre-compression evaluation parameters of blend and compress the blend in single rotary compression machine.

·       Check the post compression evaluation parameters of prepared floating tablets.

 

Table 2: Febuxostat Floating tablets formulation

Ingredients (mg)	F1	F2	F2	F4	F5	F6	F7	F8	F9	F10
Febuxostat	98	98	98	98	98	98	98	98	98	98
HPMC K4 M	25	-	-	-	-	50	-	-	-	-
HPMC K100 M	-	25	-	-	-	-	50	-	-	-
Guar Gum	-	-	25	-	-	-	-	50	-	-
Carbopol 934	-	-	-	25	-	-	-	-	50	-
Polyox N-60K	-	-	-	-	25	-	-	-	-	50
Lactose DCL 11	195	195	195	195	195	170	170	170	170	170
Sodium Bicarbonate	40	40	40	40	40	40	40	40	40	40
Citric Acid	20	20	20	20	20	20	20	20	20	20
PVP K30	10	10	10	10	10	10	10	10	10	10
Magnesium Stearate	4	4	4	4	4	4	4	4	4	4
Talc	8	8	8	8	8	8	8	8	8	8
Total Weight (mg)	400	400	400	400	400	400	400	400	400	400

 

Table 3: Febuxostat Floating tablets formulation

Ingredients (mg)	F11	F12	F13	F14	F15	F16	F17	F18	F19
Febuxostat	98	98	98	98	98	98	98	98	98
HPMC K4 M	75	-	-	-	-	-	-	-	-
HPMC K100 M	-	75	-	-	-	-	-	-	-
Guar Gum	-	-	75	-	-	-	-	-	-
Carbopol 934	-	-	-	75	-	25	25	50	75
Polyox N-60K	-	-	-	-	75	25	50	50	50
Lactose DCL 11	145	145	145	145	145	170	145	120	95
Sodium Bicarbonate	40	40	40	40	40	40	40	40	40
Citric Acid	20	20	20	20	20	20	20	20	20
PVP K30	10	10	10	10	10	10	10	10	10
Febuxostat	98	98	98	98	98	98	98	98	98
HPMC K4 M	75	-	-	-	-	-	-	-	-
HPMC K100 M	-	75	-	-	-	-	-	-	-
Magnesium Stearate	4	4	4	4	4	4	4	4	4
Talc	8	8	8	8	8	8	8	8	8
Total Weight (mg)	400	400	400	400	400	400	400	400	400

Evaluation of Floating Tablets^5,6,7

Weight variation test:

Weight variation test was performed by taking 20 tablets of each batch and weighed using a balance. The average weight and standard deviation were recorded.

 

Hardness:

The hardness of three tablets was determined using the Monsanto hardness tester and the average values were calculated.

 

Thickness:

The thickness of the tables was determined by using digital Vernier calipers. Three tablets were used, and average values were calculated.

 

Friability:

The friability of the tablets was measured in a Roche Friabilator. Tablets of a known weight (W₀) or a sample of 10 tablets are dedusted in a drum for a fixed time (100 revolutions) and weighed (W) again. Percentage friability was calculated from the loss in weight as given in equation as below.  The weight loss should not be more than 1 %. Determination was made in triplicate.

          W_{o –} W

% Friability = –––––––––––––––––x 100

                    W_o

 

Drug content:

Ten tablets were weighed individually, and the drug was extracted in 0.1 N HCl, filter through 0.45m membrane. The absorbance was measured at 315 nm after suitable dilution using a Shimadzu UV-1700 UV/Vis double beam spectrophotometer.

 

In vitro buoyancy studies:

The in vitro buoyancy was determined by using dissolution testing apparatus USP type-1.The tablets were placed in 900 ml 0.1 N HCL at 100 rpm basket rotation at 37±0.5ºC. The time require for tablets to ascend to the surface of dissolution medium and time taken by tablet to buoyant on surface of medium was recorded as floating lag time and total floating time.

 

Swelling index:

The swelling index of tablets was in 0.1 N HCL. Tablets were weighed individually named as W₀ and then it is placed in separately in glass beaker containing 200 ml 0.1N HCL at 37±0.5ºC.At periodical time interval tablets were removed from beaker and extra amount of surface water discarded by blotting paper and then tablets were weighed and it is referred as W_t and swelling index was calculated using following formula:

 

                                   W_t – W₀

Swelling index = --------------------               

                                       W₀        

 

where W_t= weight after swelling

W₀= weight before swelling

Where, W₀ is the initial weight of tablet, and W_t is the weight of the tablet at time t.

 

In Vitro Dissolution Studies:

USP apparatus II was used to test the dissolution profile using 900ml of 0.1N HCl as dissolution medium at 50rpm and 37^◦C ± 0.5^◦C. Six tablets from each batch were placed into respective basket containing HCl. 5ml of the sample was withdrawn hourly for 12 hrs. The sample was filtered and from the filtrate 3ml was withdrawn. The volume was adjusted to 100ml with 0.1N HCl. Absorbance of the solution was measured using UV spectrophotometer at 315nm

 

Drug Release Kinetic Study:

Data obtained form in vitro drug release studies were fitted to Disso calculation software. The kinetic models used are zero order, first order, Korshmers and papps, Hexoncrowell, and Higuchi equation.

 

The rate and mechanism of release of drug from the prepared tablets were analyzed by fitting the dissolution data into the zero-order equation:

 

Q = k₀t

 

Where, Q is the amount of drug released at time t, k0 is the release rate constant. The dissolution data fitted to the first order equation:

 

ln (100–Q) = ln100 –K₁t

 

Where, k1 is the release rate constant. The dissolution data was fitted to the Higuchi’s equation:

 

Q = k₂t_1/2

 

Where, k2 is the diffusion rate constant.

 

The dissolution data was also fitted to Korsmeyer equation, which is often used to describe the drug release behavior from polymeric syste       

 

Log (Mt/M∞) = log k + n log t

 

Where Mt is the amount of drug released at time t, M∞ is the amount of drug release after infinite time, K is a release rate constant incorporating structural and geometric characteristics of the tablet, n is the diffusion exponent indicative of the mechanism of drug release.

 

Stability Study:

Optimized Batch of prepared floating tablet subjected to accelerated stability studies at 40 °C and 75% RH for 1 month in a humidity chamber. The tablets of best batch were packed in aluminum foil pouch and analyzed for floating behavior and in-vitro drug release study.^8,9,10

 

3. RESULTS AND DISCUSSION:

Characterization of Drug

Results of API characterization are given in below table 4

 

Table 4: API characterization

 

Table 5: Pre-Compression Parameters of Formulation F1-F19

Formulation	Bulk density (g/ml) (n=3)	Tapped density (g/ml) (n=3)	Carr’s index (%) (n=3)	Hausner’s ratio (n=3)	Angle of repose (θ°) (n=3)
F1	0.54 ± 0.02	0.61 ± 0.03	11.48 ± 0.01	1.13 ± 0.02	17.25 ± 0.05
F2	0.48 ± 0.03	0.52 ± 0.05	7.69 ± 0.02	1.08 ± 0.01	19.22 ± 0.08
F3	0.47 ± 0.05	0.55 ± 0.03	14.55 ± 0.04	1.17 ± 0.02	21.12 ± 0.07
F4	0.57 ± 0.07	0.60 ± 0.04	5.00 ± 0.07	1.05 ± 0.01	19.26 ± 0.08
F5	0.47 ± 0.04	0.54 ± 0.04	12.96 ± 0.05	1.15 ± 0.02	25.15 ± 0.07
F6	0.42 ± 0.05	0.54 ± 0.02	16.00 ± 0.06	1.19 ± 0.02	21.15 ± 0.05
F7	0.51 ± 0.08	0.56 ± 0.05	8.93 ± 0.04	1.10 ± 0.01	19.56 ± 0.04
F8	0.52 ± 0.02	0.58 ± 0.04	10.34 ± 0.05	1.12 ± 0.01	18.75 ± 0.03
F9	0.47 ± 0.04	0.54 ± 0.02	12.96 ± 0.05	1.15 ± 0.01	17.84 ± 0.03
F10	0.58 ± 0.03	0.65 ± 0.03	10.77 ± 0.02	1.12 ± 0.01	19.29 ± 0.05
F11	0.49 ± 0.04	0.58 ± 0.08	15.52 ± 0.03	1.18 ± 0.02	22.14 ± 0.08
F12	0.47 ± 0.05	0.54 ± 0.08	12.96 ± 0.04	1.15 ± 0.02	21.04 ± 0.07
F13	0.48 ± 0.06	0.59 ± 0.07	18.64 ± 0.02	1.23 ± 0.01	18.56 ± 0.05
F14	0.58 ± 0.05	0.64 ± 0.05	9.38 ± 0.03	1.10 ± 0.01	17.45 ± 0.06
F15	0.48 ± 0.04	0.53 ± 0.06	9.43 ± 0.05	1.10 ± 0.02	16.84 ± 0.04
F16	0.43 ± 0.03	0.49 ± 0.04	12.24 ± 0.06	1.14 ± 0.01	19.84 ± 0.06
F17	0.46 ± 0.07	0.52 ± 0.07	11.54 ± 0.02	1.13 ± 0.01	21.54 ± 0.04
F18	0.51 ± 0.03	0.57 ± 0.05	10.53 ± 0.04	1.12 ± 0.02	23.45 ± 0.05
F19	0.50 ± 0.02	0.59 ± 0.07	15.25 ± 0.08	1.18 ± 0.01	21.15 ± 0.02

 

Based on above results, it concluded that the API has a poor flow in nature. Hence, it is required to use directly compression grade material which has granular material itself. For this purpose, lactose DCL 11 grade was selected. The proposed formulation was gastroretentive dosage form targeted for 12 hrs so the solubility of API in 0.1 N HCl checked. The API was found soluble in the acidic medium. Hence, solubility enhancement not required.

 

Calibration curve of febuxostat prepared by a solution of 10µg/ml of Febuxostat was scanned in the range of 200 to 400nm. The drug exhibited a λmax at 315 nm in simulated gastric fluid pH 1.2.

 

Evaluation of Formulation F1-F19 of Febuxostat Floating Tablets:

Pre-Compression Parameters Evaluation: Powder blend of formulation F1-F19 checked for pre compression parameters like, Bulk density, Tapped density, Compressibility index (CI)/Carr’s index, Hausner’s ratio, Angle of repose.

 

From the below table it is observed that bulk density found between 0.43-0.55 g/ml and tapped density found between 0.50-0.62g/ml. 

 

Hausner’s ratio value is less than 1.25 for all formulation means all the formulation has good flow properties. And it favors to do with direct compression method for tablet preparation.

 

Post Compression Parameters Evaluation:

·       Weight variation:

Weight variation results of Formulations F1-F19 showed in table 6 So, it was predicted that all the formulation exhibited uniform weight with low standard deviation values within the acceptable variation as per IP.

 

·       Thickness:

Thickness of Formulations F1-F19 showed in table 6. No any major difference observed in formulation batches

 

·       Hardness:

It was observed that all the formulation has a good hardness and increase in polymer amount will increase the hardness of tablet. All Formulations have good strength to withstand the mechanical shocks.

 

·       Friability:

All formulation has a friability value less than 1 %, so this shows the durability of the prepared tablets.

 

·       Drug Content:

Formulations F1-F19 results of Drug Content found within the limit. No any deviation observed.

 

·       Swelling Index :

Water Intake ratio or swelling index of Formulations F1-F19 results are given in table 7 shows that all formulations has a good swelling capacity so it’s good for a floatin.

 

·       Floating Lag time and Total floating time:

All the formulations have floating time within 1 min. so it is as per our requirement for floating tablet. Also, the total floating time is up to 12 hr. for all formulations.

 

Table 6: Post Compression Parameters of Formulation F1-F19

Formulation	Weight variation (mg) (n=3)	Thickness (mm)(n=3)	Hardness (Kg/cm2) (n=3)	Friability (%)
F1	401±1.5	5.51±0.09	5.13±0.15	0.48
F2	400±1.4	5.59±0.11	4.72±0.07	0.70
F3	402±1.5	5.50±0.12	5.26±0.22	0.36
F4	399±1.6	5.52±0.11	5.13±0.15	0.49
F5	398±1.7	5.51±0.11	5.15±0.15	0.50
F6	400±1.8	5.48±0.13	4.76±0.17	0.68
F7	401±1.5	5.52±0.14	5.16±0.13	0.57
F8	398±1.4	5.51±0.12	5.19±0.11	0.52
F9	399±1.4	5.51±0.10	5.15±0.06	0.59
F10	401±1.5	5.50±0.13	5.29±0.13	0.50
F11	400±1.6	5.49±0.14	4.76±0.11	0.41
F12	401±1.7	5.47±0.08	5.08±0.11	0.59
F13	402±1.8	5.51±0.09	5.23±0.12	0.54
F14	398±1.7	5.48±0.11	4.86±0.15	0.49
F15	399±1.8	5.47±0.06	5.06±0.17	0.60
F16	402±1.6	5.49±0.11	4.75±0.14	0.81
F17	403±1.7	5.52±0.14	5.41±0.10	0.42
F18	401±1.8	5.50±0.15	5.13±0.09	0.45
F19	402±1.4	5.54±0.11	4.06±0.12	0.69

 

Table 7: Post Compression Parameters of Formulation F1-F19

Formulation	Drug Content (%) (n=3)	Swelling Index (%) (n=3)	Floating Lag Time(sec) (n=3)	Total Floating Time (hr.) (n=3)
F1	99.2 ± 0.3	58.2 ± 4.4	70 ± 3	6 ± 1
F2	99.8 ± 0.4	62.5 ± 2.2	95 ± 5	6 ± 1
F3	98.5 ± 0.5	54.6 ± 5.3	63 ± 2	6 ± 1
F4	97.8 ± 0.7	51.6 ± 6.2	45 ± 3	6 ± 1
F5	99.5 ± 0.5	62.4 ± 4.3	64 ± 4	6 ± 1
F6	99.4 ± 0.4	68.5 ± 5.2	72 ± 4	8 ± 1
F7	99.5 ± 0.5	72.1 ± 1.6	83 ± 9	8 ± 1
F8	99.7 ± 0.6	68.6 ± 3.2	64 ± 2	8 ± 1
F9	98.4 ± 0.4	69.4 ± 2.5	56 ± 4	8 ± 1
F10	100.5 ± 0.5	68.5 ± 3.2	62 ± 8	8 ± 1
F11	100.8 ± 0.4	67.4 ± 3.6	186 ± 4	12 ± 1
F12	98.7 ± 0.2	66.5 ± 5.6	165 ± 3	12 ± 1
F13	99.5 ± 0.3	69.7 ± 3.9	170 ± 5	12 ± 1
F14	98.6 ± 0.4	78.5 ± 2.9	120 ± 5	12 ± 1
F15	99.7 ± 0.5	71.5 ± 3.4	144 ± 6	12 ± 1
F16	99.4 ± 0.7	75.2 ± 2.5	136 ± 3	12 ± 1
F17	98.7 ± 0.4	74.1 ± 4.5	178 ± 2	12 ± 1
F18	99.8 ± 0.5	85.6 ± 5.6	32 ± 8	12 ± 1
F19	99.4 ± 0.2	76.2 ± 4.1	140 ± 8	12                   ± 1

 

In Vitro Drug Release Study:

In vitro drug release study results are given in table 6.6. Results shows that low amount of polymer in tablet does not release drug up to 12 hr at starting. As we can see that in F1-F5, amount of polymer in tablet was just 25 mg. due to this F1-F5 does not give release up to 12 hr and release observed up to 8 hr only.

 

After increasing the amount of polymer in formulation F6-F10 give the sustained effect up to 10 hr. so again amount of polymer increased to achieve desired release up to 12 hr and finally F11-F19 gives release up to 12 hrs. But here objective not achieved because in 12-hour maximum drug should be release. Results shown that after increasing polymer amount up to 75mg in single polymer more than 95% drug release not achieved in 12 hr. also the floating lag time was observed more than 1 min in F1-F20 formulation.

 

Further trials taken with a combination of two polymers. In combination batches F16-F19, batch F18 gives maximum % drug release 99.7% in 12 hr. also the floating lag time observed 32 seconds which was lowest in all formulations. Also, total floating time was 12 hr so main floating parameters of floating tablets fulfill by combination of Carbopol 934 and Polyox N-60K. So the best combination of polymer based on % drug release, floating time and total floating was F18 which contains Carbopol 934 and Polyox N-60Kboth 50mg.

 

Initially trials were taken with single polymer. In single polymer trials, Carbopol 934 and Polyox N-60Kgive good sustained effect up to 12 hr so based on that, combination of polymer tried and both polymers in combination give max % drug release of 99.7%. So F18 formulation finalized as optimized formulation.

 

Figure 1: Comparison of % Drug release of Formulation F1-F12            Figure 2: Comparison of % Drug release of Formulation F13-F19

 

Table 8: % Drug release study of Formulation F1-F19

Code	% Drug Release
	1	2	3	4	6	8	10	12
F1	26.8±0.1	45.7±0.2	68.9±0.1	84.4±0.5	89.4±0.3	98.6±0.8	-	-
F2	36.2±0.3	48.4±0.5	59.7±0.5	80.5±0.4	91.7±0.6	99.5±0.8	-	-
F3	45.8±0.5	59.7±0.4	69.7±0.4	89.4±0.5	95.4±0.4	99.8±0.7	-	-
F4	52.4±0.7	74.5±0.5	81.6±0.7	94.5±0.7	97.8±0.3	98.9±0.2	-	-
F5	39.8±0.8	48.7±0.6	66.4±0.8	79.9±0.8	89.4±0.2	99.1±0.7	-	-
F6	25.5±0.7	39.4±0.4	49.7±0.3	75.4±0.9	81.5±0.7	88.7±0.8	99.5±0.2	-
F7	30.4±0.7	45.8±0.7	65.4±0.4	79.4±0.4	81.4±0.6	94.5±0.6	98.7±0.1	-
F8	32.1±0.5	46.1±0.2	65.4±0.5	74.8±0.5	87.4±0.5	95.6±0.5	99.4±0.2	-
F9	45.6±0.3	68.4±0.5	74.8±0.8	81.4±0.3	84.5±0.3	91.9±0.3	98.7±0.2	-
F10	29.4±0.4	41.2±0.2	59.4±0.7	72.1±0.1	84.5±0.2	89.1±0.7	99.8±0.7	-
F11	30.5±0.2	35.6±0.6	40.5±0.9	58.9±0.2	75.1±0.5	80.7±0.2	84.9±0.8	91.6±0.6
F12	27.5±0.6	30.5±0.5	32.8±0.2	49.7±0.4	56.7±0.4	59.7±0.5	74.8±0.5	88.4±0.4
F13	8.4±0.4	18.6±0.7	20.8±0.7	36.7±0.5	48.9±0.3	74.4±0.4	79.4±0.3	81.2±0.5
F14	11.8±0.8	17.8±0.8	22.7±0.8	29.9±0.6	38.4±0.5	49.4±0.6	69.7±0.1	78.4±0.8
F15	20.4±0.2	39.7±0.2	64.7±0.3	78.0±0.2	87.9±0.2	89.4±0.2	91.7±0.7	92.4±0.7
F16	18.9±0.6	27.6±0.5	38.7±0.6	52.4±0.3	69.8±0.8	81.7±0.3	84.7±0.8	88.9±0.2
F17	24.1±0.5	32.5±0.4	39.4±0.5	45.7±0.5	74.7±0.7	79.8±0.8	85.2±0.6	90.2±0.5
F18	33.5±0.3	39.2±0.8	45.5±0.3	48.7±0.5	64.7±0.2	75.4±0.6	88.9±0.5	99.7±0.2
F19	29.4±0.6	60.1±0.7	65.8±0.2	69.4±0.8	75.4±0.4	78.9±0.6	80.5±0.5	82.7±0.5

 

Drug release kinetic study:

The drug release data of the final batch F18 was fitted in to different kinetic models. Among all, the best fitted model explained by Higuchi model because R² value of Higuchi model has 0.984.

 

Table 9: Kinetic modeling data of batch F18

Kinetic Model	Parameters	Value
Zero Order	R2	0.932
First Order	R2	0.730
Higuchi	R2	0.984
Korsmeyer-Peppas	R2	0.527
Hixon Crowell	R2	0.910

 

Higuchi model was found to best describe the R² (coefficient of determination). Korsmeyer-Peppas equation also best suits the dissolution data where the values of “𝑛” were 0.45-0.89 indicating anomalous, non-Fickian, or nearly zero-order release mechanism. Drug release mechanism from prepared floating tablets of F18 batch was elucidated by fitting the in vitro dissolution data in Korsmeyer-Peppas equation. The value of “𝑛” for the optimized formulation was greater than 0.45 indicating non-Fickian case II transport mechanism.

 

Comparison with marketed product:

Final batch F18 was compared with the marketed product. The dissolution profile was shown below. As the marketed formulation was only conventional tablet hence it gives release more than 85% after 30 min.

 

Table 10: Comparison with marketed formulation

Time in Hours	F18	FABULAS
1	33.5±0.3	95.9±1.6
2	39.2±0.8	99.9±0.5
3	45.5±0.3	-
4	48.7±0.5	-
6	64.7±0.2	-
8	75.4±0.6	-
10	88.9±0.5	-
12	99.7±0.2	-

 

Figure 3: Comparison of F18 formulation with Marketed product

 

4. CONCLUSION:

floating drug delivery systems are easiest approach for technical and logical point of view among gastro retentive drug delivery system, so for present study, floating drug delivery system was chosen to increase the gastric residence time of dosage form which led to increased bioavailability of various drug substances. Febuxostat is the drug of choice for treatment of Gout. So in present investigation, an attempt was made to deliver Febuxostat via floating drug delivery system to the vicinity of absorption site by prolonging the gastric residence time of the dosage form. Tablets were subjected to various evaluation parameters such as hardness, friability, thickness, weight variation, drug content, floating property study, swelling study, in vitro drug release study. It was revealed that tablets of all batches had acceptable physical parameters. The effervescent-based gastro retentive drug delivery is a promising approach to achieve in vitro buoyancy by using gel-forming polymer HPMC K4M, HPMC K100M, Carbopol 934 P, Gellan gum and Polyox N-60 K and gas generating agent sodium bicarbonate. Fourier transform Infrared spectroscopy confirmed the absence of any drug/polymers/excipients interactions. The drug content of all the formulations was found to be in the range of 96.22% to 99.45%, which indicates the uniform drug content. In vitro floatability studies revealed that most of the tablets still floated for more than 12 hours because of their low densities. In vitro drug release studies were performed for all the prepared formulations. All the prepared floating tablets exhibited good drug release. Amount of polymer in floating tablet plays an important role in drug release. Low amount of polymer in formulation doesn’t make a tablet to release a drug up to 12 hr. Hence F18 formulation in combination of Polyox N-60K and Carbopol 934 P makes tablet float and release a drug up to 12hr.  The drug release data of formulation F18 fitted to different kinetic models and the best fitted model was Higuchi model. Formulation F18 found stable up to 1 month stability condition.Hence, formulation F18 was the optimized formula

 

5. ACKNOWLEDGMENT:

The Author and co-author, thanks to Saraswati Institute of Pharmaceutical Sciences, for providing the necessary facility to accomplish the work we also humble gratitude to our colleague and non-teaching staff for their support during the work.

 

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