1. INTRODUCTION:

For many drugs, solid oral dosage forms are still the most popular formulation and are commonly preferred over other delivery methods. In comparison to what is possible with conventional measurement approaches, the mechanical testing, characterization, and monitoring techniques needed for controlled-drug delivery systems are typically more demanding. Due to its simplicity of administration, oral ingestion has long been the most practical and frequently used route of drug delivery. Modified release dosage forms of the same drug may provide one or more benefits over immediate release formulations, as is well known. Modified release dosage forms for oral administration can be created in a variety of ways, from simple film-coated pellets, tablets, or capsules to more complex and sophisticated delivery systems like osmotically driven systems, ion exchange mechanisms, three-dimensional printing systems, and electrostatic deposition systems. Modified release drug products are typically designed to provide slow, continuous drug delivery over the course of the entire dosing interval while also enhancing patient compliance and convenience. This helps to optimise a therapeutic regimen. Comparing bilayer tablets to traditional monolayer tablets, there are a few significant benefits. For instance, these tablets are frequently used to prevent physical separation of formulation components from chemical incompatibilities. In addition, by combining layers with different release patterns or slow-release and immediate-release layers, bilayer tablets have made it possible to develop controlled delivery of active pharmaceutical ingredients with predetermined release profiles.¹

Figure 1. Bilayer Tablet.

1.1. THE ADVANTAGES OF THE BI-LAYER TABLET DOSAGE FORM ARE:

1. They are unit dosage forms and provide the best oral dosage form capabilities for the most precise dosing and the least content variability.

2. It is less expensive than any other oral dosage form.

3. More portable and light.

4. The easiest and most affordable to package and strip.

5. Easy to swallow with minimal hang-up potential.

6. Coating techniques can hide offensive odours and bitter tastes.

7. Well suited for industrial production.

8. The best oral dosage form in terms of chemical and microbial stability.

9. When using a punch face with an embossed or monogrammed design, product identification is quick and simple and doesn't require any additional steps.

1.2. DISADVANTAGES OF BI-LAYER TABLET DOSAGE FORM ARE:

1. Patients who are unconscious or children may have difficulty swallowing.

2. Due to their amorphous and low density characteristics, some drugs resist compression into dense compacts.

3. It may be challenging to formulate or manufacture a tablet for a drug that has poor wetting, slow dissolution, or optimal absorption that is high in the GIT while maintaining adequate or full drug bioavailability.\

4. Drugs that are sensitive to oxygen, have an offensive odour, or are bitter may need to be coated or encapsulated.²

1.3. NEED OF BILAYER TABLETS:

· Create innovative drug delivery systems, such as chewing devices and floating tablets for gastro-retentive drug delivery, to extend the life cycle of drug products and administer fixed dose combinations of various APIs.

· Regulating the rate at which one or two distinct active pharmaceutical ingredients are delivered.

· To create swellable/erodible barriers for modified release by modifying the total surface area available for the API layer by sandwiching it with one or two active layers.

· To separate Active Pharmaceutical Ingredients (APIs) that are incompatible from one another and to regulate API release from one layer by making use of the functional property of the other layer (such as, osmotic property).³

1.4. CHARACTERIZATION OF BILAYER TABLET:

· Particle size distribution: A sieving method was used to measure the particle size distribution.

· Photo-microscope study: A photo-microscope image (X450 magnifications) of TGG and GG was taken.

· Angle of repose: Using the diameter of the powder cone as a starting point, the following equation was used to determine the angle of repose. Tan ø=h/r Where h is the height and r is the powder cone's radius.

· Moisture sorption capacity: All disintegrates have the ability to absorb moisture from the environment, which affects medications that are moisture sensitive. One gramme of the disintegrate was used to measure the capacity for absorbing moisture. uniformly distributed in petri dishes, maintained at 37°C and 100% relative humidity for two days, and the amount of moisture uptake was examined using the difference in weights.

· Density: The following formulas were used to calculate the loose bulk density (lbd) and tapped bulk density (tbd). Weight of the powder divided by 1/4 equals packing volume divided by TBD 14 of the powder's weight equals 3 times the packing's tapped volume.

· Compressibility: Using Carr's compressibility index, the disintegrate's compressibility index was calculated. C = 100 x (1-þb/þt).⁴

2. LIMITATIONS OF LAYERED TABLET:

1. Capping.

2. Hardness problem.

3. Layer Separation.

3. BILAYER TABLETS: QUALITY AND GMP REQUIREMENTS:

The chosen press must be able to:

1. Prevent capping and separation of the two individual layers that make up the bilayer tablet in order to produce a quality bilayer tablet in a validated and GMP manner.

2. Providing a hard enough tablet.

3. Keeping the two layers from becoming contaminated with one another.

4. Creating a distinction between the two layers that is clearly visible.

5. High output

6. Accurate and unique control of the two layers' weight.⁵

4. VARIOUS TECHNIQUES FOR BILAYER TABLET:

4.1. OROS® Push Pulls Technology:

It has two or three layers, of which one is the push layer and the other is the drug's necessary layer. The drug layer is made up of the drug and two or more different agents. As a result, the medication in this layer is in a poorly soluble form. Osmotic and suspending agents can also be included. The tablet core is surrounded by a semi-permeable membrane (Figure 2).⁶

Figure No. 2: Bilayer OROS push pull technology.

4.2. L-OROS TM Technology:

The solubility issue was addressed by this system. Alza created the L-OROS system, which involves manufacturing a lipid soft gel product that contains a drug in a dissolved state and coating it with a barrier membrane, an osmotic push layer, a semi-permeable membrane, and a hole for an exit orifice (Figure 3)⁷

Figure No. 3: L–OROSTM Technology.

4.3. EN SO TROL Technology:

An approach to drug delivery that emphasises identification and incorporation of the identified enhancer into controlled release technologies is used to increase solubility or to create optimised dosage forms.⁸

Figure No. 4: EN SO TROL Technology.

4.4. DUROS Technology:

The phrase "Miniature drug dispensing technology" is another name for this system. It works like a tiny syringe, dispensing the drug over an extended period of time in a continuous and consistent manner in a small concentrated form. With the aid of an external reservoir made of a cylinder of high impact titanium alloy, drug molecules are shielded from enzymes.⁹

4.5. DUREDAS™ Technology:

With the aid of this technology, drugs can be released in either an immediate or sustained manner. This system offers two drugs with a combination release pattern or one drug with a different release pattern. Different release patterns were achieved in this system by combining hydrophilic polymers. This technology offers a number of benefits, such as the combination release in a single tablet or the incorporation of two drugs in a single dosage form. Immediate release granulate is compressed first during the process of making a bilayer tablet using DUREDASTM Technology, then a sustained release layer.¹⁰

4.6. Geminex Technology:

This can significantly improve the therapeutic effectiveness of medications and reduce side effects. This technology delivers one or more medications in a single dosage form at various release rates. Both industry and patients find it to be very helpful. Pen West actively uses Geminex Technology in the following conditions: diabetes, cardiovascular disease, cancer, and CNS disorders.¹¹

5. THE BILAYER TABLET USED A VARIETY OF APPROACHES:

5.1. Floating Drug Delivery System:

The floating drug delivery systems are a logical and easy-to-develop method for creating gastro-retentive dosage forms from a formulation and technological standpoint (GRDFs).¹²

5.2. Approaches To Design Floating Drug Delivery System:

The design of floating dosage forms for single- and multiple-unit systems has been done using the following strategies.¹³

5.3. Intra Gastric Bilayered Floating Tablets.:

These are also compressed tablets with immediate and sustained release in two layers, as shown in the figure.¹⁴

5.4. Multiple Unit Type Floating Pills:

These systems are made up of double layers surrounding sustained release pills that act as "seeds". Effervescent agents make up the inner layer while swellable membrane layers make up the outer layer. The system sinks instantly when submerged in dissolution medium at body temperature, then forms swollen pills that resemble balloons and float because they have a lower density.¹⁵

5.5. Polymeric Bio Adhesive System:

These are made to absorb liquid after administration so that the outer layer hardens into a viscous substance that sticks to the mucus layer of the stomach. While the adhesive forces are being reduced, this should promote gastric retention. These are made up of two layers, one with immediate dosing and the other with bioadhesive capabilities.

Advantages: Due to differences in mucous amounts and consistency between animals and humans, the success seen in animal models with this system has not been translated to human subjects.¹⁶

5.6. Swelling System:

These are made to be small enough when administered that swallowing the dosage form won't be challenging. They quickly swell or disintegrate after ingestion and pass through the pylorus until the required level of drug release has been reached. The straightforward bilayer tablet might have one layer for immediate release and another for extended release.¹⁷

6. APPLICATIONS OF BILAYER TABLETS:

1) Modify total surface area.

2) Control the delivery rate.

3) Provide synergic property.

4) Provide the agonistic property.

5) Administer fixed dose combination.

6) Bilayer technology is suitable for sequential release of two drugs in combination.

7) Separate Two Incompatible drug Substances.

8) Bilayer tablet is improved beneficial technology to overcome the shortcoming of the single layered tablet.

9) Bilayer tablets are used to deliver the loading dose and sustained dose of the same o rdifferent drugs.

10) Sustained release tablet in which one Layer is immediate release as initial dose and second layer is maintenance dose.¹⁸

6.1. MODIFY THE TOTAL SURFACE AREA OF APIS:

To create swellable/erodible barriers for modified release, bilayer tablets are designed to reduce the total surface area of active pharmaceutical ingredients by sandwiching them between one or two inactive layers.¹⁹

6.2. CONTROL THE DELIVERY RATE:

The bilayer tablet is used to regulate the rate at which one or two distinct active pharmaceutical ingredients are delivered. Bilayer tablets with different controlled releases are created. The active ingredient, dosage (mg), and timing of the immediate and sustained release layers are listed in Table No. 1 for the bilayer tablets.

Nitazoxanide bilayer tablets were developed by Anupamsachan N et al. (2017) for dual drug delivery. Controlled release is the second layer after immediate release in the first layer. One layer's super disintegrant was sodium starch glycolate, and the polymer for the layer with controlled release was HPMC 15. Due to an increase in the number of super disintegrants, the in vitro release study found that the maximum release occurred in 2 hours (or 24%), whereas in controlled release, it occurred at the 12th hour (95%).²⁰

For the treatment of hypertension, Jayaprakash S et al. (2011) created bilayer tablets of amlodipine besylate and metoprolol succinate. While Metoprolol Succinate was created for sustained release using HPMC 100 and HPMC K4 M polymers, the Amlodipine layer was created for immediate release using sodium starch Glycolate and pregelatinized starch as the super disintegrant. The IR layer displayed an initial release after 1 minute and 5 seconds and 99.24% dissolution at the end of 30 minutes, as well as a sustained release after 20 hours and 90.46% dissolution. The formulations' kinetic studies showed that dissolution is the main mechanism of drug release.²¹

PamuSandhya et al. (2014) provided an explanation of the preparation and assessment of wet granulation- and direct compression-produced bilayer tablets of glimepiride and metformin hydrochloride. In the layer for immediate release, sodium starch glycolate was used, and in the layer for sustained release, ethyl cellulose N 50, HPMC 100 M. The results showed that 98.44% of the dissolution occurred in immediate release at the end of the 15th minute and 98.63% occurred in sustained release at the end of the 12th hour.

The formulation and characterization of bilayer tablets of candesartan cilexetil for the treatment of hypertension were covered by Dr. Vijayakuchana et al. (2017). For the sustained release of Candesartan, sodium alginate, HPMC 100 M, and ethyl cellulose are used in addition to Crospovidone, a super disintegrant. A 99.85% drug release in 12 hours was the outcome.²²

Extended-release Rosuvastatin Calcium and Fenofibrate were discussed as a combination therapy in Lokesh Kumar et al(2016).'s bilayer tablet study. Cross carmellose sodium and sodium starch glycolate are two super disintegrants that are used in the immediate release. The sustained release layer contains HPMC K4 M and microcrystalline cellulose. The study found that the sustained release layer of Rosuvastatin disintegrated in 12 hours, while the sustained release layer of Fenofibrate disintegrated in 97.5% of the time.²³

Allopurinol with sustained release and Telmisartan with immediate release were combined to create bilayer tablets, which Navesh Veer et al. (2018) evaluated. The first layer is the sodium and sodium starch glycolate immediate release layer, and the second layer is the HPMC and microcrystalline cellulose sustained release layer. According to the findings, the cumulative percentage release during in-vitro dissolution is 100.7% in 30 minutes and 99.4% at 12 hours.

Bilayer tablets of propranolol hydrochloride were designed and evaluated, according to China Niranjanpantra et al. (2007). The immediate release layer contained water immiscible polymers like ethyl cellulose, Eudragit RLPO, and Eudragit RSPO, while the sustained release layer contained super disintegrant sodium starch glycolate. According to the findings, the sustained release layer released 30% of the propranolol hydrochloride within 12 hours and the dissolution study's first 15 minutes.²⁴

Bilayer tablets of lornoxicam were created and tested by Metkar Vishal et al. in 2012. The first layer uses the super disintegrant Ac-di sol for immediate release, and the second layer uses HPMC k4 M and HPMC k 100 M for sustained release. The SR layer revealed 98% of dissolution in 24 hours while the IR layer revealed 24.10% in an hour.

Propranolol Hydrochloride bilayer tablet formulation and evaluation were discussed by Momin Shahanoor et al. in 2017. Crosspovidone, a super disintegrant, was used in the IR layer and ethyl cellulose in the SR layer. At the 12th hour, the SR layer showed a dissolution rate of 87.40%.²⁵

6.3. PROVIDE SYNERGIC PROPERTY:

Drugs can be combined in a bilayer tablet to produce a synergistic effect. Glipizide and metformin hydrochloride sustained release matrix bilayer matrix tablets were created and tested by Rajeev Sharma et al. in 2014. Glipizide appears to lower blood glucose abruptly by stimulating the release of insulin from the pancreas, and metformin HCl improves glucose tolerance in patients with Type II diabetes by reducing hepatic glucose production, intestinal glucose absorption, and by improving insulin sensitivity by increasing peripheral glycemia. Both medications are used to treat diabetes by providing synergistic action by different mechanisms.²⁶ Each medication has a sustained release. Since metformin hydrochloride has a high dose (500 mg), it is highly water soluble, which makes it difficult to formulate the drug with an extended release rate and may make it difficult to manage the initial burst of the drug from such a formulation. As a result, both medications are incompatible with one another, necessitating the development of a system to prevent close contact between them, namely a sustained release bilayer tablet formulation of glipizide and metformin HCl using a variety of polymers at various concentrations, including hydroxyl propyl methyl cellulose K15 M, hydroxy ethyl cellulose, and hydroxy methyl cellulose.²⁷

6.4. PROVIDE AGONISTIC EFFECT:

Due to the fact that the use of immediate-release metoclopramide improves the absorption of sustained-release diclofenac sodium, Surendra G Gattani et al. (2012) developed the combination of diclofenac sodium and metoclopramide in a single tablet for the treatment of a migraine. who, especially when suffering from a migraine, has slower absorption due to gastric stasis. This found that because bilayer tablets of MTH and DS allow for the sequential release of the two medications, they may be an effective migraine treatment.²⁸

Table No: 1 Bi layer tablet with key ingredient²⁹

AUTHOR	IMMIATE RELEASE LAYER			SUSTAINED RELEASE LAYER
AUTHOR	Functional ingredient	Amount in mg	Release pattern	Functional ingredient	Amount in mg	Release pattern
Anupam et al.	Sodium starch glycolate	9 mg	25 % in 2 hour	HPMC HPMC E15	2.5 mg 170 mg	95 % in 12^th hour
Jayaprakash S et al.	Sodium starch glycolate	5 mg	99.24% in 30 min	HPMC100 HPMC K4 M	75 mg 15 mg	90.46 % in 12^th hour
Pamusandhya et al.	Sodium starch glycolate	9 mg	98.44 % in 15 min	HPMC 100 M	160 mg	98.63 % in 12^th hour
Vijayakuchana et al.	Cross povidone	8 mg	---	HPMC 100 M Ethyl cellulose	20 mg 20 mg	99.85 % in 12^th hour
Lokeshkumar et al.	Sodium starch glycolate Cross carmellose sodium	7.70 mg 15.60 mg	97.5 % in 30 min	HPMC K 4 M	90 mg	12 hour
Naveesh veer et al.	Sodium starch glycolate	25 mg	100.7 % in 30 min (% cumulative release)	HPMC	90 mg	99.4 % in 12^th hour
Chinamniranjanpathra et al.	Sodium starch glycolate	2.5 mg	30 % in 15 min	Ethyl cellulose eudragit RLPO eudragit RSPO	55 mg 82.5 % 82.5 %	12 hour
Metkarvishal et al.	Cross carmellose sodium	18 mg	24.10% in 1 hour	HPMC K 4 M HPMC 100 M	50 mg 25 mg	98 % in 24 hour
Momin Shahanoor	Cross carmellose sodium	1 mg	---	Ethyl cellulose	165 mg	87.40 % in 12^th hour

Table No: 2 Administer fixed dose combination³⁰

Author	Immediate release layer		Floating layer
Author	Functional ingredient	Release pattern	Functional ingredient	Release pattern	Lag time
R.P Swain et al.	Sodium starch Glycollate	96%within 15 min.	HPMCk 100	12 hour	9 min.
Nawar M Toma et al.	Cross Carmellose Sodium	Within30 min.	HPMC, Ethyl cellulose, Carbapol	6 hours	60 sec
P.H. Wakde et al.	Sodium starch Glycolate	---	Guar gum, Pectin	98.97% in 14 hour	8 min
Shiv Kumar et al.	Sodium starch Glycolate	100.1% in 0.3 hour	HPMC, Microcrystalline cellulose	98.9% in 12 hour	71 sec

6.5. TO ADMINISTER FIXED DOSE COMBINATION:

Combination products, also referred to as fixed-dose drug combinations, combine two or more active medications into a single dosage form. The drug product life cycle is extended and novel drug delivery systems, such as chewing devices, buccal or mucoadhesive delivery systems, and floating tablets, gastro-retentive delivery, are created to administer fixed-dose combinations of various APIs. The immediate and floating layers of the bilayer tablets are described in Table No. 2 along with the functional ingredient and release patterns.³¹

7. EVALUATION OF BI-LAYER TABLETS:

1. Thickness.

2. Hardness.

3. Size and shape.

4. Uniformity of weight.

5. Friability.

6. Wetting time.

7. Water absorption ratio.

8. Dissolution study.

1. Thickness: Thickness and diameter of tablets were important for uniformity of tablet size. Using a venire calliper, thickness and diameter were measured.

2. Hardness: The limit of hardness of MDT is usually kept in lower range to facilitate early disintegration in mouth. The hardness of MDTS may be measured using hardness tester (Monsanto Hardness tester).

3. Size and shape: Size and shape of the tablet can be dimensionally described, monitored and controlled.³²

4. Uniformity of weight: Weight variation test is done as per standard procedure. Ten tablets from each formulation are weighed using an electronic balance and the average weigh are calculated.

5. Friability: The strength of a tablet is measured by its friability. Twenty tablets were weighed accurately and placed in the tumbling apparatus that revolves at 25 rpm dropping the tablets through a distance of six inches with each revolution. The tablets were weighed after 4 minutes to determine the percentage of weight loss. % loss = [(Initial wt. of tablets –Final wt. of tablets)/ Initial wt. of tablets] ×10019.

6. Wetting time: Five circular tissue papers of10 cm diameter are placed in a petridish with a 10 cm diameter. Petridish is mixed with ten millimetres of a water-soluble dye called Eosin. The tissue paper is carefully placed on top of the tablet. Wetting time is defined as the amount of time needed for water to reach the tablet's upper surface.³³

7. Water Absorption Ratio: A piece of tissue paper folded twice was placed in a small Petri dish containing 6 ml of water. On a tablet, the paper was placed, and the amount of time needed for complete wetting was recorded. The wetted tablet was then weighed.

R = 10 (Wa /Wb), where Wa is the weight of the tablet after water absorption and Wb is the weight of the tablet before water absorption, was used to calculate the water absorption ratio (R).³⁴

8. Dissolution Study: Bilayer tablets were subjected to in vitro drug release studies in simulated gastric and intestinal fluids to assess their ability in providing the desired controlled drug delivery. Drug release studies were carried out using USP dissolution test apparatusI at 100 rpm, 37±0.5°C, and pH 1.2 buffer (900 ml) (i.e. 0.1 N HCl) for 2 hours, since The typical gastric emptying process takes two hours. The experiment was carried out for an additional 10 hours with pH 6.8 phosphate buffer in place of the dissolution medium. 5 ml of each sample was taken out and replaced with 5 ml of a drug-free dissolution medium at various time intervals. The samples were taken out and put through a UV spectrophotometer's multi component mode of analysis.³⁵

8. CONCLUSION:

Bilayer tablets have made it possible to develop controlled-drug delivery systems with predetermined release patterns or slow-release and immediate-release layers. Modified release dosage forms of the same drug may provide one or more benefits over immediate release formulations, as is well known.

9. REFERENCE:

1. Abebe A, Akseli I, Sprockel O, Kottala N, Cuitiño AM. Review of bilayer tablet technology. International Journal of Pharmaceutics. 2014; 461(1-2):549-558.

2. Y.W. Chien, Fundamentals of controlled-release of drug administration in: J. Swarbrick (Ed.), Novel Drug Delivery System Marcel Dekker, New York, 1982, pp. 465–574.

3. P. Buri, F. Puisicux, E. Doelker, J.P. Benoit, Formes Pharma centiques Nouvelles, Ed. Technique et Documentation, Lavoisier, Paris, 1985.

4. I.R. Wilding, A.J. Coupe, S.S. Davis, The role of gamma scintigraphy in oral drug delivery, Adv. Drug Deliv. Rev. 1991; 7: 87– 117.

5. Vishwakarma A.G, Mogal R.T, Pawar A.Y et al. Bilayer Tablet - A New Ways in Oral Drug DeliverySystem.International Journal of Pharma Tech Research. 2014; 6(5): 1416-1428.8.

6. Lende Lathika K, Benerjee S.K, Gadhave M.V et al. Review on: Bilayer Floating Tablet. Asian Journal of Pharmaceutical Research and Development. 2013; 1(1): 31-39.9.

7. Rudnic EM. Kottke et al MK Tablet dosage form. Modern Pharmaceutics. 72: 369.

8. Muzzio F.J., Lerapetritou M., Portillo P., Llusa M., Levin M., Morris K.R., Soh L.P.J., McCann R.J., Alexander A. A forward-looking approach to process scale-up for solid dose manufacturing. In: Augsburger, L.L., Hoag, S.W. (Eds.), Pharmaceutical Dosage Forms: Tablets, Volume 3: Manufacture and Process Control. 2008.

9. Kulkarni A, Bhatia M; Development and evaluation of bilayer floating tablets of atenolol and lovastatin for biphasic release profile. Iranian Journal of Pharmaceutical Research, 2009; 8(1): 15-25.

10. Panchel HA, Tiwari AK; A Novel approach of bilayer tablet Technology-A Review. 2012; 3(5): 44-49.

11. Nirmal J, Saisivam S, Peddanna C, Muralidharan S, Godwinkumar S, Nagarajan M; Bilayer tablets of atorvastatin calcium and nicotinic acid: formulation and evaluation. Chem Pharm Bull., 2008; 56(10):1455-1458.

12. The Indian Pharmacopoeia. Volume 2, 4^th edition, The Controller of Publication, Govt. of India, Delhi, 1996: A82-A85. The United States Pharmacopoeia, United states Pharmacopoeial Convention, Inc., Rockville, MD, 2000:1944.

13. C. Gopinath, V. Hima Bindu, M. Nischala. An overview on bilayered tablet technology. Journal of Global Trends in Pharmaceutical Sciences. 2013; 4 (2): 1077-1085.

14. Anupam Sachan N and Ankita Gupta. Formulation and Evaluation of Bilayer Tablets of Nitazoxanide. Der Pharmacia Lettre [http://scholarsresearchlibrary.com/archive.html]. 2017; 9[7]:1-9.

15. S. Jayaprakash, S. Mohamed Halith, K. Kulathuran Pillai, et al; Formulation and evaluation of bilayer tablets of amlodipine besilate and metprolol succinate. Der Pharmacia Lettre. 2011; 3(4): 143-154

16. Pamu. Sandhya, Faheem Unnisa Begum, Afreen. Formulation and Evaluation of Bilayer Tablets of Glimepiride and Metformin HCL. IOSR-Journal of Pharmacy and Biological Sciences. 2014); 9(1) :38-45.

17. Vijaya Kuchana, Ayesha Farooqui, Peddireddy, et al; Development and characterization of bilayer tablets of candesartan cilexetil. Indo American Journal of Pharmacy. 2017; 3 (6): 338-346.

18. Lokesh Kumar, M. Vijay Kumar and Gaurav Tiwari, Combinational therapy of Rosuvastatin calcium and Fenofibrate as bilayer tablet: A potential approach to control hypolipidemia. International Journal of Pharmaceutical Sciences and Research. 2016; 7(1): 413-428.

19. Navesh Veer, Lal Ratnakar Singh and Lalit Kumar Tyagi. Formulation and evaluation of bilayer sustain release tablet of Allopurinol and Telmisartan for the treatment of hyperuricemia associated with hypertension. World Journal of Pharmacy and Pharmaceutical Sciences. 2018; 7(5): 1189-1209.

20. Chinamniranjan Patra, Arethibharani Kumar, Hemant Kumarpandit, et al; Design and evaluation of sustained release bilayer tablets of propranolol hydrochloride. Acta Pharm. 2007; 57: 479–489.

21. Metkar Vishal, Kumar Anuj, Pant Pankaj, etal; Formulation, development and evaluation of Bilayer tablets of Lornoxicam. International Journal of Drug Development & Research. 2012; 4(2): 173-179.

22. Momin Shahanoor, Khan Shadab, Ghadage D.M., Yadav et al; Formulation and evaluation of bilayer tablet of propranolol hydrochloride. Journal of Drug Delivery & Therapeutics. 2017; 7(2): 50-57.

23. Rajeev Sharma, Naresh Kalra, Rahul Gupta et al; Development and evaluation of sustained release bilayer matrix tablet of glipizide and metformin hydrochloride. International Journal of Drug Research and Technology. 2014; 4 (1): 1-13.

24. Surendra G. Gattani, Sohan S. Khabiya, Jitendra R. Amrutkar. Formulation and Evaluation of Bilayer Tablets of Metoclopramide Hydrochloride and Diclofenac Sodium. PDA Journal of Pharmaceutical Science and Technology. 2012; 66(2): 151-160.

25. Dhanish Joseph, Golda Maria Thomas, A Review on Current Applications of Bilayer Tablets, Research Journal of Pharmacy and Technology. 2019:12(5): 2539-2544.

26. Kulkarni, S. Novel decongestant bilayer tablets in modified release dosage form using HPMC. Indian Journal of Pharmaceutical Sciences. 2000; 5: 508-509.

27. Vogeleer, J. Bilayer tablets; why special technology is required The Courtoy R292F tablet press, designed for quality bilayer tablets. Niro Pharma Systems. 1997; 56: 76-82.

27.27. Kaushik SK, Easwari TS, Sharan G, Sharma A. Novel Approach of Bilayer Tablet Technology: A Review, International Journal for Pharmaceutical Research Scholars. 2014: 3(4).

28. Shirwalkar AA, Kumar SM and Jacob S. Recent developments in floating drug delivery systems for gastricretention of drugs, an overview. Indian Drugs. 2006; 43(9): 697-704.

29. Verma RK and Garg S. Drug delivery technologies and future directions. Pharmaceutical Technology. 2001; 25(2): 1-14.

30. Breech AJ, Lucisano L and Franz RM. Investigation into substrate cracking of a film coated bilayered tablet. Journal of Pharmacy and Pharmacology. 1998; 40: 282 – 283.

31. Varaiya C. Bi-layer neutraceutical tablets: Rewards and challenges. Journal of Pharmacy and Pharmacology. 2005; 40: 282 – 283.

32. Panchal HA and Tiwari AK. A Novel approach of bilayer tablet technology-A review, International Research Journal of Pharmacy. 2012; 3(5): 152-156

33. Sadhu Venkateswara Rao, Bopparaju Priyanka and Kantamneni Padmalatha, a Review on Bilayer tablet technology: A novel approach, GSC Biological and Pharmaceutical Sciences. 2019; 7(2): 22–28.

34. Kalam MA, Humayun M, Parvez N, Yadav S, Garg A, Amin S, Sultana Y, Ali A. Release kinetics of modified pharmaceutical dosage forms: a review. Cont J Pharm Sci. 2007; 1: 30-35.

35. Zamorano J, Edwards J. Combining antihypertensive and antihyperlipidemic agents–optimizing cardiovascular risk factor management. Integrated Blood Pressure Control. 2011; 4: 55-71.

36. Mr. Vivek M. Satpute, Dr. Punit R. Rachh, bi-layer tablet: a controlled release dosage form. International Journal of Research and Analytical Reviews. 2020; 7(1) 330-343.

36.

Received on 28.10.2023 Modified on 01.12.2023

Asian J. Pharm. Tech. 2024; 14(1):43-49.

DOI: 10.52711/2231-5713.2024.00009