INTRODUCTION:

The easiest and most popular approach for administering drugs is orally. Due to the painless oversight, this technique has a high level of complaint sufficiency. Because constructing a dosage form for the oral route of administration is more flexible than designing a dosage form for other routes, it has garnered more attention in the pharmaceutical industry. The majority of oral controlled drug delivery systems use diffusion, dissolution, or a combination of the two mechanisms to release the drug into the Gastrointestinal Tract (GIT) in a controlled manner.

By using information about the drug profile, such as the dose, absorption characteristics, and the required quantity of the drug, one can calculate the desired release rate of the drug from a controlled release dosage form. Drugs with short half-lives and easy G.I.T. absorption are swiftly removed from the blood circulation. The development of oral controlled release formulations, which slowly release the medication into the gastrointestinal tract and maintain a steady level of medication in the serum for a longer period of time, was done in order to prevent this issue. Oral medication delivery systems make up more than half of all market-available drug delivery systems. The ease of administration and patient acceptance are two clear benefits of these systems. One would always prefer to have perfect drug delivery systems with two key characteristics: For the length of the treatment, there will be just one dose, and the active medication will be delivered right where it is needed systemic gastro retention Additionally, including certain medications into a gastric retention system will not improve their absorption, such as isosorbide dinitrate, which is absorbed equally efficiently throughout the GI tract. Using gastro-retentive devices can help some medications work better. These include medications that have a local effect in the stomach, are mostly absorbed there, are poorly soluble at an alkaline pH, have a constrained window of absorption, and disintegrate in the colon. Any drug delivery system should aim to deliver a therapeutic dose of medication to the right parts of the body, reach and maintain the desired therapeutic drug concentration quickly enough to cause the desired pharmacological activity, and reduce the likelihood and intensity of undesired side effects. It would be more desirable and practical to keep the dose frequency to a once or, at most, twice daily schedule in order to accomplish this goal. A properly created prolonged release dosage form could be a significant step forward in this area.

Basic Gastrointestinal tract physiology:

In both human and veterinary applications, it is well known that inclination can be exploited as a storage space for sustained-release (SR) dose formulations. The fondues, body, and antrum are the three anatomical sections of the stomach (pylorus). The proximal portion, which is composed of the fundus and body, serves as a holding area for undigested matter, whereas the antrum is the primary location for mixing motions and functions as a pump to complete stomach emptying. Both when one is fasting and when one is fed, the process of stomach emptying takes place, but the patterns of motility in the two states are very different. It is characterised in the fasting states by an interdigestive series of electrical events that cycle through the stomach and intestine every two to three hours. This is called the interdigestive myloelectric cycle or migrating myloelectric cycle (MMC).¹

MATERIALS AND METHODS:

Materials:

Nabumetone, Hydroxy propyl methyl cellulose (K4M, K15M), polyvinylpyrrolidine, Magnesium stearate, Iso propyl alcohol, Hydrochloric acid, Talc, citric acid and gas generating agent such as sodium bicarbonate were used as other ingredients. All reagents used were of analytical grade.

Methods:

Nabumetone Floating tablets were prepared by wet granulation method using polymers (HPMC K15M, and HPMC K100M) by changing drug to polymer ratio as 1:1, 1:1.5, and 1:2. Sodium bicarbonate and citric acid used as generating agents. Lactose used as diluents and PVP K30 used as granulating agent with isopropyl alcohol as solvent. Nabumetone and all other ingredients were weighed separately and passed through sieve no. 25.²

50% of the lubricants, polyvinylpyrrolidine, HPMC (K15M, K100M), and the active component were combined. After that, the mixture was crushed to create the compacts in a slugging machine. After that, the compacts were ground and put through sieves 18 and 60. The particles taken as granules on sieve no. 60 were those that were retained, while those that passed through the sieve were fines. The particles were once more pressed, ground, and sieved through sieves numbers 18 and 60.³Until the granules and fines were achieved in a ratio of approximately 60:20, the cycle of compaction, milling, and sieving was repeated. The remaining ingredients—all save magnesium stearate—were added, and the granules and fines were again combined. The remaining lubricant i.e. magnesium stearate was then added and mixed to the above mixture to form the final blend. The final blend was compressed into tablets using single punch tablet rotary press.⁴

Evaluation of Floating Tablets^5-7

Evaluation of Flow Properties of granules before compression:

· Angle of repose (Ө):

The funnel method was used to calculate the angle of repose of the granules. A funnel was used to collect the precisely weighed granules. The height of the funnel was set so that the tip of the funnel just reached the top of the granules' mound. The funnel was opened up so that the grains could freely pour out onto the surface. The powder cone's diameter was measured, and the angle of repose was determined using the equation below. Tan θ = h/r where the powder cone's height and radius are indicated, respectively, by h and r.

Fig 1: Measuring angle of repose

· Bulk density:

We calculated the loose bulk density (LBD) and tapped bulk density (TBD). Each formula's 2gm of powder was added to a 10ml measuring cylinder after being lightly shaken to break up any agglomerates that may have formed. After the initial volume was measured, the cylinder was allowed to drop by itself from a height of 2.5cm onto a hard surface at intervals of 2 seconds. Once there was no longer any loudness change, the tapping was stopped. The following equations were used to calculate LBD and TBD. Powder weight divided by packing volume is known as the LBD. TBD = powder's weight divided by packing's

Carr’s index (%) = [(TBD - LBD) x 100] / TBD

· Haussler’s ratio:

Hausner’s ratio can be determined by Hausner’s ratio = TBD / LBD

Where, TBD - Tapped Bulk Densities, LBD - Loose Bulk Density

Evaluation of tablets after compression:^8-10

· Size of the floating tablets:

The thickness and Diameter of each tablet is measured by using vernier calipers. It is measured in mm.

· Uniformity of Weight:

Twenty tablets were prepared in each formulation, weighed individually to check for weight variation. IP limit for weight variation in case of tablets.

· Hardness:

The hardness of the tablet was determined using a Monsanto hardness tester. It is expressed in Kg/cm2

· Friability:

The tablets are weighed and the weight is compared to the initial weight after four minutes of this therapy, or 100 revolutions. A measurement of the tablet's friability is the loss through abrasion. The amount is given as a percentage (%).

· Drug content:

In a volumetric flask filled with 100ml of 0.1 Hcl (solvent), a tablet containing 40mg of the active ingredient (drug) is dissolved. The solvent is given time to dissolve the medication. The solution has been filtered, and 1ml of the filtrate was used to make up the entire 50ml of the volumetric flask's capacity with the solvent. Spectrophotometric analysis was performed on the produced solution. A percentage (%) is used to represent the medication's composition.

Buoyancy studies:

The floating lag time was calculated as the amount of time needed for the tablet to float to the surface. The amount of time the dosage form consistently stayed on the medium's surface was calculated as the total floating time. The tablets were placed in 900ml plastic containers with 500ml of 0.1 N HCl to observe the tablets' in vitro floating behaviour (pH 1.2, 37.5 o C). Visual observation was used to calculate the floating lag times and floating durations of the tablets.

Fig.2: Floating tablet in 0.1N Hcl showing floating lag time

RESULT AND DISCUSSION:

Preformulation Studies:

Physical Appearance Test:

Based on physical visual test, it is a white to off-white crystalline substance.

Melting point determination:

The melting point of Nabumetone was determined by melting point apparatus and result found to be 79-81°C

· Solubility Determination

Table 1 Solubility of Nabumetone

Solvent	Solubility of Nabumetone	Remark
Water	0.00199 mg/ml	Practically Insoluble
Ethanol	26 mg/ml	Soluble

· Determination of wavelength using UV-visible spectroscopy

Fig. 3: UV Spectra of Nabumetone

· Calibration curve of Nabumetone

Table 2 Absorbance of different concentration of Nabumetone

S. No.	Concentration (µg/ml)	Absorbance at 332 nm
1	2	0.020
2	4	0.035
3	6	0.055
4	8	0.071
5	10	0.092
6	12	0.121
7	14	0.141
8	16	0.159

Figure 4: Calibration curve of Nabumetone

Evaluation of Nabumetone floating tablet

· Hardness

Table 3: Hardness of different formulation

S.No.	F-1	F-2	F-3	F-4	F-5	F-6	F-7	F-8	F-9
1	3	5	4	4	4	4	4	5	5
2	3	4	6	4	5	4	5	6	4
3	5	5	4	5	5	5	5	5	5
4	3	4	4	5	4	3	5	6	4
5	5	3	5	3	4	3	5	6	5
Aveg. Hardne -ss Kg/cm²	3.7	4.1	4.2	4.3	4.6	4.8	4.8	5.7	4.6

· Weight variation

Table 4 Weight variation of different formulation

Tablet no.	Formulations
Tablet no.	F-1	F-2	F-3	F-4	F-5	F-6	F-7	F-8	F-9
1	390	430	454	475	528	574	658	659	543
2	398	422	452	475	530	570	660	665	547
3	392	426	450	480	525	580	662	670	549
4	394	422	459	467	523	578	659	669	548
5	398	430	456	470	530	572	654	670	546
6	397	423	458	476	524	578	658	662	543
7	390	430	454	475	528	574	658	659	543
8	398	422	452	475	530	570	660	665	547
9	392	426	450	480	525	580	662	670	549
10	394	422	459	467	523	578	659	669	548
11	398	430	456	470	530	572	654	670	546
12	397	423	458	476	524	578	658	662	543
13	392	426	450	480	525	580	662	670	549
14	394	422	459	467	523	578	659	669	548
15	398	430	456	470	530	572	654	670	546
16	397	423	458	476	524	578	658	662	543
17	398	430	456	470	530	572	654	670	546
18	398	430	456	470	530	572	654	670	546
19	398	430	456	470	530	572	654	670	546
20	392	426	450	480	525	580	662	670	549
Avg.	395.25	426.15	454.95	473.45	526.85	575.4	657.95	667.05	546.25

S. No.	Formulation	Floating lag time in (sec.)	Floating time (hr)
1.	F-1	54-75	≥9
2.	F-2	64-69	≥9
3.	F-3	79-85	≥9
4.	F-4	60-70	≥9
5.	F-5	65-75	≥9
6.	F-6	84-91	≥9
7.	F-7	78-89	≥9
8.	F-8	3 min.45 sec.-15 min.20 sec.	≥9
9.	F-9	4 min. 20 sec-10 min.45 sec	≥9

Time (hr)	F1	F2	F3	F4	F5	F6	F7	F8	F9
0.5	20	16.4	18.1	12.8	15.3	11.1	10.5	17.8	18.1
1	28.9	25.1	28.4	20.4	29.1	25.8	23.8	29.8	30
2	38.4	41.2	45.1	35.7	42.1	39.7	35	45.7	44.7
3	50	51.7	55.1	47.1	52.8	47.5	45.9	50.7	51.6
6	75	74.6	72.7	69.4	71	63.7	62.9	74.1	73.9
9	90.9	88.1	83.5	83.3	82.7	75.1	70.4	88.7	89.1

Formulation and Evaluation of Floating Tablet of Nabumetone

RESULT AND DISCUSSION:

Preformulation Studies:

Physical Appearance Test:

Based on physical visual test, it is a white to off-white crystalline substance.

· Solubility Determination

Figure 4: Calibration curve of Nabumetone

Evaluation of Nabumetone floating tablet

· Hardness

· Weight variation

Table 4 Weight variation of different formulation

· Friability

· Buoyancy determination

· In vitro dissolution:

CONCLUSION:

S.No.	Formulations	Friability
1.	F-1	0.3%
2.	F-2	0.4%
3.	F-3	0.3%
4.	F-4	0.2%
5.	F-5	0.3%
6.	F-6	0.5%
7.	F-7	0.4%
8.	F-8	0.2%
9.	F-9	0.3%

Formulation and Evaluation of Floating Tablet of Nabumetone

RESULT AND DISCUSSION:

Preformulation Studies:

Physical Appearance Test:

Based on physical visual test, it is a white to off-white crystalline substance.

· Solubility Determination

­­Figure 4: Calibration curve of Nabumetone

Evaluation of Nabumetone floating tablet

· Hardness

· Weight variation

Table 4 Weight variation of different formulation

· Friability

· Buoyancy determination

· In vitro dissolution:

CONCLUSION:

Figure 4: Calibration curve of Nabumetone