INTRODUCTION:

By release the drug slowly in the stomach and upper gastrointestinal tract (GIT), a gastroretentive drug form improves the probability to absorption.

A wide range of approaches, including floating drug delivery systems (FDDS), high density DDS, mucoadhesive systems, swelling and expanding DDS, modified shape systems, and other delayed gastric devices, have been put in to control the gastric residence of drug delivery systems in the upper portion of the GIT.

A gastroretentive dosage form (GRDF) termed FDDS may prolong the gastric residence time (GRT) (Xu et al., 2006). FDDS is suitable for drugs that act locally in the stomach, with an absorption window in the stomach or upper small intestine and are weakly soluble or unstable in the intestinal fluid as to produce an acceptable amount of the drugs bioavailability (Bardonnet et al., 2006; Whitehead et al., 1998). The usual period of gastric residence is five minutes to two hours. The four phases of the migrating myoelectric complex (MMC) are as follows: Phase I: No contraction for 40–60 minutes; Phase II: Intermittent contractions for 20–40 minutes; Phase III: frequent contractions at the most frequency that travel very far, commonly referred to as the "housekeeper wave." (10–20 minutes) and phase IV, the period that passes as between phase III and I (0–5 minutes) (Wilson et al., 2000). Tablets offer many merits, that include as the most stable the dose form until it's dry, be cheap to manufacture and cheap to buy, give an excellent patient compliance rate, and with an extended shelf life. Bilayer floating tablets as an initial step to minimize the chemical incompatibility of API by physical separation and allowing the production of different drug release choices among them rapid release and longer release (Parveen et al., n.d.).

Because floating DDS have a lower bulk density than GIT fluids, they will concentrate and float in stomach fluid without affecting the GIT emptying rate over an extended length of time. In addition, the medicine releases sluggishly at the necessary rate and stays afloat on the food's surface while the system remains buoyancy on the gastric fluid (GI fluid). There are numerous floating systems that depend on tablets, powders, granules, capsules, laminated films, empty microspheres. DDS floating in the medication is achieved by incorporating a floating chamber that is pressurized, evacuated, or filled with an inert gas via the system. The stomach's residual system was emptied when the medication was released. This could result in an extended period of stomach retention and effective management of variations in plasma medication concentration. In addition to the side with the lowest gastric content necessary to ensure correct implementation of the lightning retention, the dose form must also be maintained with the lowest possible degree of floating force. Due to physiological abnormalities, the entire system is plagued by numerous problems, such as a narrow absorption index for specific medications, altered stomach emptying times, and drug instability in the intestines (CHOURASIYA et al., 2021)

1. FLOATING DRUG DELIVERY SYSTEM:

Since FDDS have a lower bulk density than gastric fluids, they float in the stomach for an extended period of time without slowing down the rate at which the stomach empties. The medication is gradually removed from the system at the desired rate while it is floating on the contents of the stomach. The stomach's residue system is emptied following medication release. Increased GRT and improved management of variations in concentrations of drugs in plasma are the outcomes of this (Reddy and Murthy, 2002)

Since the floating extended-release dosage forms are able to keep their low apparent density while the polymer hydrates and forms a gelled barrier at the outer surface, they are referred to as "hydrodynamically balanced systems" (HBS) and exhibit most of the properties of hydrophilic matrices. Just like in the case of traditional hydrophilic matrices, the medication is gradually released from the enlarged matrix. Because these forms have a lower bulk density than the stomach contents, it is anticipated that they will remain buoyant on the stomach contents for three to four hours without influencing the intrinsic pace of emptying. Of the several hydrocolloids suggested for formulations using floating forms, cellulose ether polymers—particularly hydroxypropyl methylcellulose (HPMC)—are the most widely used. To add buoyancy and reduce the rate of water intake, the formulation can include fatty material whose bulk density is less than one. To extend the GR (Stomach Retention) Period for oral dose forms, many strategies are used. This low bulk density floating system will be in the floating state within the stomach. They have more time to reserve the medicine. Such a system can reduce adverse effects and improve drug safety, which will boost the medicine's bioavailability (Shah SH et al., n.d.). To extend the GR (Gastric Retention) Period for oral dose forms, many strategies are used. This low bulk density floating system will be in the floating state within the stomach. They have more time to reserve the medicine. Such a system can reduce side effects and improve drug safety, which will boost the medicine's bioavailability (Niharika et al., 2018).

Fig.1 Bilayer floating tablet

2. NEED FOR GASTRIC RETENTIVE DRUG DELIVERY SYSTEM:

To reduce the erratic stomach emptying process and to extend the medication release. When a medication is taken orally, the dosage form is kept in the stomach for a long time and then releases the drug there in a way that prolongs its release, allowing the drug to be released continuously to its absorption sites, which are in the upper gastrointestinal retentive part. Drugs in dosage form have a longer gastric residence time (GRI) because they can be stored in the stomach area for extended periods of time. The need for gastro retentive doses (GRDFs) has prompted significant efforts to expand these delivery systems in the academic and industrial domains(Dube et al., 2014).

The following approaches formed the basis for the design of the GRDFs that resulted from these efforts.

a) A high-density tablet that stays in the bottom portion of the stomach for a longer amount of time.

b) The dose form with low density that makes gastric fluids (GF) float.

c) Adhesion to the mucosa of the stomach(Pandey et al., 2012).

Fig.2 Conventional Dosage Form shows negligible absorption whereas in GRDDS drug is continuously absorbed

3. ADVANTAGES OF FLOATING BILAYER TABLET:

1. This technique offers the sustained release concept of HBS, which is proven to be unaffected by the specific medication's absorption site.

2. It keeps the therapeutic window as optimal as possible, enabling controlled release of the medicine.

3. For medications like furosemide and riboflavin, which are packaged as floating systems, site-specific drug delivery is obtained.

4. Improved drug regimen efficacy is attained by improved patient compliance.

5. It kept the blood level steady.

6. They are more stable in comparison to other oral methods.

7. Provides maximum accuracy and little content homogeneity.

8. Conceptually flexible.

9. Suitable for manufacturing on a large scale.

10. The application of a coating technique can conceal an unpleasant taste and odor.

11. Tablet swallowing is simple.

12. Simpler and more portable

13. Inexpensive(Hejazi and Amiji, 2003; Wu et al., 1997)

4. DISADVANTAGES OF FLOATING BILAYER TABLET:

1. To keep the system afloat, the stomach has to contain more fluid.

2. Drugs that have issues with solubility and stability in the stomach are not designed.

3. Medications that irritate the stomach mucosa are not designed for that purpose.

4. Certain medications, such isosorbidedinirate, which are equally absorbed via the GIT, are not recommended for integration into the gastric retention system.

5. The layer may separate as a result of inadequate bonding.

6. One of the main issues with bilayer tablets is capping.

7. Hardness is a further issue.

8. There's a possibility of layers blending together.

9. Swallowing issues in patients who are unconscious or children.

10. Problems with bioavailability may occur when there is insufficient dissolving properties and poor wetting (Singh and Kim, 2000).

5. APPLICATIONS OF FLOATING BILAYER TABLET:

1. The optimum use for bilayer technology is the sequential delivery of two medications together.

2. Divide the Two Drug Substances That Are Incompatible.

3. To address the shortcomings of the single-layered tablet, the bilayer tablet was improved.

4. Consistent dosage of the exact same with different medications (Strom, 2010).

6. EVALUATION TECHNIQUES OF FLOATING BILAYER TABLET

· Pre-compression parameters:

1. Angle of Repose

The angle of repose can be used to estimate frictional forces in powder. The greater angle of repose which can exist between the powder surface and the horizontal plane, or height, the better.

tan θ=h/r

θ= tan^-1h/r

Where the height (h) and radius (r) of the pile must be used to determine the angle of repose.

2. Bulk Density (BD):

It is the overall mass of powder per bulk volume. The weighed powdered (passed through standard sieve #20) was poured into a measuring cylinder, and the initial volume was recorded. The bulk volume is the original volume. Based on this, bulk volume is computed using the following formula. It is provided by and expressed as g/cc.

B=m/Vo

Where,

m= mass of the powder

Vo= bulk volume of the powder

3. Tapped density(TD):

It is the whole mass of powder per tapped volume. The powder was tapped 500 times to determine the volume. The tapped volume was then recorded after 750 times of tapping (the difference between both of these volumes must be less than 2%). If the difference is greater than 2%, tap is done 1250 times, and the volume of each tap is recorded. It is provided by and stated in g/cc.

TD= m/Vi

Where,

m= mass of powder

Vi= tapped volume of the powder

4. Housner’s Ratio (H. R):

It is a measurement of the drug's frictional resistance. The ratio of the tapped density to bulk density was used to estimate the ideal range, which is 1.2 to 1.5.

H.R= TD/BD

5. Compressibility index (C. I.):

By comparing the powder's bulk density (BD), taped density (TD), and packing rate, one can assess the powder's flowability. This formula was used to determine the compressibility index (Saikrishna, n.d.; Salatin et al., 2022; Santhanalakshmi et al., 2012).

C.I = 100 (1-1/H.R)

· Post-Compression parameters:

1. Thickness and Diameter:

A Vernier Calliper or Screw Guage is used to measure the tablet's diameter.

2. Weight variation test:

The weight variation involves selecting twenty tablets at random, calculating the weight variation, comparing it to the IP standard, and determining the average weight.

3. Hardness:

Expressed in kg/cm2, and it is determined by selecting three tablets at random from a Monsanto hardness tester. When handling tablets, the ability of the tablet to withstand mechanical shock is determined in part by its hardness.

4. Friability:

The Friabulator (Roche Friabilator) will be used to assess friability by randomly selecting 10 tablets, weighing them, and then putting them in the machine at 25 rpm for four minutes. Following resolution, the tablets are ready to be weighed and dusted(Narendra et al., 2006; Patel et al., 2012).

The following formula can be used to calculate friability.

Friability % = W1-W2/W1 X 100

Where,

W1 = Weight of tablets (Initial weight/Before tumbling)

W2 = Weight of tablets (Final weight / After tumbling)

5. Disintegration Time (D. T):

Each testube used for the disintegration test apparatus held one tablet, and the test was conducted at 37°C in a beaker filled with buffer (0.1N HCl or phosphate buffer solution with a pH of 6.8). Disintegration time is the length of time it takes for a medication to dissolve.

6. Dissolution study:

Using a USP paddle apparatus, the dissolution test was carried out by maintaining a temperature of 37ºC for 50 rpm (rotation per minute). After that, 0.5 ml of the sample was removed at a separate time interval, and the 5 ml of solution was swapped out with 5 ml of a buffer solution(Dinakaran et al., 2011).

7. Floating lag time:

The time it took the tablets to begin floating. Less than one minute should be the upper limit. A dissolving device with 0.1 N HCl (900 ml) was used to identify it.

8. Floating time:

The whole amount of time needed for a tablet to float in medium (Dinakaran et al., 2011).

CONCLUSION:

GRDDS enhance the bioavailability of medications with a small absorption window by allowing the drug to enter the upper section of the GIT continuously and for an extended period of time. The main focus of pharmaceutical research is drug release. Both immediate and sustained release, as well as a 24-hour extension of sustained release, can be achieved with floating bilayer tablet

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Received on 23.12.2023 Modified on 13.01.2024

Res. J. Pharma. Dosage Forms and Tech.2024; 16(1):42-46.

DOI: 10.52711/0975-4377.2024.00007