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135ADVANCEMENTS IN DRUG DELIVERY: A COMPREHENSIVE REVIEW OF BILAYER TABLETS VIA MICROSPHERE TECHNOLOGY
Dr. Harikiran Lingabathula
Professor, Department of Pharmacology, Princeton College of Pharmacy, Hyderabad, Telangana, India
Soorammagari Sunayana
Asst. Professor, Department of Pharmacology, Princeton College of Pharmacy, Hyderabad, Telangana, India
Abstract - The development of bilayer tablets with immediate release and sustained release microspheres on one layer is the goal of this work. The purpose of the proposed dosage form is to reduce the frequency with which an anti-diabetic medication is administered at the same time. For a variety of reasons, several pharmaceutical companies are currently developing bi-layer tablets: marketing, therapeutics, and patent extension, to name a few.
When developing and manufacturing such tablets, existing but modified tablet presses are frequently utilized to reduce capital expenditure. Utilizing microspheres, or microparticles, as drug carriers is one such strategy. It is the reliable method for maintaining the desired concentration at the site of interest and delivering the drug to the target site with specificity in the event that it is altered. Microspheres received a lot of attention for their extended release as well as their ability to target anti-diabetic medications. The microsphere-based bilayer tablet represents a new era in the successful development of controlled release formulations and includes a number of features that make it an effective drug delivery system. especially when a high output of production is also required. This review article aims to educate society about the most recent technological advancements in bilayer and floating drug delivery systems.
Keywords: Microsphere, anti-diabetic bilayer tablet, Floating drug delivery system.
1 INTRODUCTION
Diabetes mellitus, also known as diabetes, is a group of metabolic diseases in which a person has high blood sugar levels either because the body does not produce enough insulin or because the cells in the body do not respond to the insulin that is produced1. This condition is commonly referred to as diabetes mellitus. Diabetes is one of the significant reasons for death and handicap on the planet. In 2000, the World Health Organization estimated that 171 million people worldwide had diabetes. By 20302, that number is expected to rise to at least 366 million. Type 2 (non-insulin dependent) diabetes is a multifaceted condition marked by an underlying insulin deficiency.
A low dose combination of two different agents reduces the dose-related risk, the addition of one agent may
counteract some deleterious effects of the other, and using low dosage of two different agents minimizes the clinical and metabolic effects that occur with maximal dosage of individual component of the combined tablet4. This insufficiency results from defective insulin utilization and can be corrected by administration of one or more of the currently available oral hypoglycemic agents.
Sidney Walter Fox was a biochemist from Los Angeles who was born on March 24, 1912, and died on August 10, 1998. He was the one who discovered how life started. Fox created what he believed to be the first
"protocells" out of proteinoids and water and investigated the synthesis of amino acids from inorganic molecules, proteinous amino acids, and amino acid polymers known as "proteinoids" from
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136 inorganic molecules and thermal energy.He called these protocells "microspheres"
and they have now been named
"protobionts." Fox suggested that the conditions in his experiments were comparable to those found in the Earth's early days and that life could have formed naturally. He demonstrated in his experiments that using thermal energy and inorganic molecules, protein-like structures can be made. After creating microspheres that, according to Dr. Fox, were very similar to bacterial cells, he came to the conclusion that these could be the earliest forms of life.
Microspheres are tiny, spherical particles with diameters ranging from one micrometer to one thousand micrometers (1 mm). Microparticles are another name for microspheres. Natural and synthetic materials can be used to make microspheres. Ceramic, polymer, and glass microspheres can all be purchased commercially. The density of solid and hollow microspheres is very different, so they are used for different things.
Typically, hollow microspheres are added to materials to reduce their density.
Depending on the material they are made of and how big they are, solid microspheres can be used for a variety of things.
The most common kinds of polymer microspheres are polyethylene, polystyrene, and expandable microspheres. Due to their ability to facilitate processes like cell sorting and immunoprecipitation, polystyrene microspheres are typically utilized in biomedical applications. Polystyrene microspheres are suitable for use in biological laboratory experiments as well as medical research due to their ability to adsorb proteins and ligands on it quickly and permanently.
Polyethylene microspheres are frequently utilized as filler, either permanently or temporarily. Polyethylene microspheres can create porous structures in ceramics and other
materials thanks to their lower melting point. Polyethylene microspheres are highly desirable for numerous research applications, including flow visualization and fluid flow analysis, microscopy techniques, health sciences, process troubleshooting, and the availability of colored and fluorescent microspheres.
Electronic paper digital displays also use charged polyethylene microspheres.
Polymer microspheres called expandable microspheres are used as a blowing agent in things like puff ink, automotive underbody coatings, and thermoplastic injection molding. They can also be used as a light filler in waterborne paints, crack fillers, and joint compound, for example. When heated, expandable polymer microspheres can grow to more than 50 times their original size.
Each sphere has a thermoplastic shell on the outside that houses a hydrocarbon with a low boiling point inside. The hydrocarbon exerts pressure on the internal shell wall as the outside shell expands and softens when heated.
Glass microspheres are primarily utilized as a filler and volumizer for the purpose of reducing weight, a retroreflector for the purpose of improving highway safety, and an additive for cosmetics and adhesives. There are only a few applications for them in medical technology. Fired microspheres are utilized essentially as crushing media.
Quality, sphericity, uniformity, particle size, and distribution of particle size all vary greatly in microspheres. Each individual application necessitates the selection of the appropriate microsphere.
1.1 Advantages of Bi-layer Tablets 1. Execution with two layers and an
optional conversion kit for one layer 2. Low price when compared to other
dosage forms.
3. Compared to other oral dosage forms, it has the highest chemical and microbial stability.
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137 4. Coating technologies can cover upunpleasant tastes and odors.
5. Flexible idea.
6. provide the lowest content uniformity while the highest precision.
7. The least amount of hangup issues and easy to swallow.
8. Suitable for mass production.
9. Bi-layer tablet is reasonable for forestalling direct contact of two medications and hence to amplify the adequacy of blend of two medications.
10. Because one of the layers can be kept as extended and the other as immediate release, bi-layer tablets can be designed to modify release.
11. Expansion of an established technology.
12. The use of feed granules with only one entity as a potential option.
13. Separation of components that are incompatible.
14. Patient consistence is worked on prompting further develop drug routine effectiveness.
1.2 Disadvantages of Bi-layer Tablets 1. Adds complexity and costs a lot for
bi-layer rotary presses.
2. Reduced yield, layer separation, and insufficient hardness
3. Individual layer weight control that is not precise.
4. There is cross-contamination among the layers.
5. Difficult to swallow in children and patients who are unconscious.
6. Due to their amorphous and low- density nature, some drugs resist being compacted.
7. Drugs with unfortunate wetting, slow disintegration properties, ideal retention high in GIT may challenging to fabricate as a tablet that will in any case give adequate medication bio accessibility.
2 VARIOUS TECHNIQUES FOR BILAYER TABLETS
Oros ® Push Pull Technology: This system is mostly made up of two or three layers, one or more of which are necessary for the drug and the other is the push layer. The drug and two or more distinct agents make up the majority of the drug layer. As a result, the drugs in this drug layer are poorly soluble.
Osmotic and suspending agents are additionally added. The tablet's core is surrounded by a semi-permeable membrane.
L-OROS Technology : Alza invented the L-OROS system, which addresses the issue of solubility. It begins with the production of a lipid soft gel product containing the drug in a dissolved state before coating it with a barrier membrane, an osmotic push layer, a semi-permeable membrane, and an exit orifice.
DUROS Technology: An outer cylindrical titanium alloy reservoir makes up the system. This reservoir protects the drug molecules from enzymes and has a high impact strength. The minuscule drug dispensing system known as DUROS technology resembles a miniature syringe and delivers a minute amount of concentrated form.
2.1 Evaluation of Bilayer Tablets
Thickness of Tablets: Using a dial caliper that has been calibrated, thickness and diameter are measured.
The formulation's three tablets are selected at random, and each one's thickness is measured.
Hardness of Tablets: The Monsanto hardness tester is used to measure hardness. Three tablets from each batch are tested.
Friability: After weighing twenty tablets, the Roche friabilator is turned for four minutes at 25 rpm. The tablets are deducted and weighed once more after each revolution. The formula will be used to determine the percentage of friability,
% F = {1-(Wt. /W)} x 100
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138 Where, % F = Friability in percentageW = Initial weight of tablet Wt. = Weight of tablets after revolution Weight Variation: Each batch contains twenty tablets, each of which is individually weighed. Twenty tablets' average weight and standard deviation are calculated. If not more than two of the individual tablet weights deviate from the average weight by more than the percentage shown in, and if none deviate by more than twice the percentage, then the batch has passed the weight variation test.
Drug Content: The assay of the drug content is carried by weighing ten tablets and calculated the average weight. Then the tablets are triturated to get a fine powder. From the resulting weighed accurately about 155 mg of the powder (equivalent to 100 mg) of metformin hcl is taken, shake with 70 ml of water for 15 minutes, dilute to 100 ml with water and filter. Dilute 10 ml of the filtrate to 100 ml with water. Further dilute 10 ml to 100 ml with water and measure the absorbance at the maximum at about 233nm.
Buoyancy Determination: One tablet from each formulation batch is placed in a USP type II dissolution apparatus containing 900 ml 0.1 N HCl dissolution medium using a paddle at a rotational speed of 75 rpm. The time it takes for the dosage form to emerge on the surface of the medium is referred to as floating lag time, and the time it takes for the dosage form to continuously emerge on the surface of the medium is referred to as total floating time (TFT). The medium is kept at a temperature of 37° 2°C. The time taken for tablet to arise on surface of medium and the term of time by which the tablet continually stay on surface of medium will be noted.
Swelling Study: The singular tablets are weighed precisely and kept in 50ml of water. After 60 minutes, the tablets are carefully removed, blotted with filter paper to remove any water on the surface,
and accurately weighed. Rate enlarging is determined by utilizing equation; The swelling study is as follows: 100 x wet weight x dry weight
In-Vitro Drug Release Study: Each batch's tablet is broken down using a paddle-operated USP type II apparatus. A dissolution vessel contains 900 milliliters of dissolution media at a temperature of 37° 2°C. Each dissolution vessel contains one tablet, and the paddle's rotational speed is set at 50 rpm. The 10 ml of test is removed at foreordained time span for 12 hours and same volume of new medium is supplanted. Using a double beam UV visible spectrophotometer, the drug content of the samples is compared to dissolution media as a blank at 233 nm.
3 CONCLUSION
The quality of bilayer tablets and GMPrerequisites can vary significantly.
Metformin and pioglitazone bilayer tablets were made in this study using modified direct compression techniques, and the drug release study yielded significant results. As a result, the formulations might be a good candidate for multiple unit administration, opening up new therapeutic options that would be extremely beneficial to the patient. These bilayer tablets are mostly made to reduce lag time, but they may also increase the drug's bioavailability by making full use of the drug and avoiding excessive plasma levels. This explains why bi-layer tablets are produced using a wide variety of presses, from straightforward single-sided presses to highly sophisticated machines.
The use of an "air compensator" in conjunction with displacement control appears to be the best option whenever high-speed production of high-quality bi- layer tablets is required.
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