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Blood glucose control is necessary for the management of diabetes mellitus, and this frequently calls for taking many daily doses of antidiabetic medications. Offering enhanced bioavailability and extended drug release, floating microspheres have emerged as a viable gastroretentive drug delivery technology for antidiabetic medications. Among the most common types, floating microspheres have several advantages. To prevent the impulses of gastric emptying and release the medication for an extended amount of time, they disperse evenly throughout the gastric fluid. Because of their ability to float in gastric fluid, these microspheres can extend their stay in the stomach and improve the absorption of medications such as metformin, glipizide, glibenclamide, sitagliptin, pioglitazone and Empagliflozin. The formulation techniques, polymers, and mechanisms underlying the flotation and sustained release of antidiabetic medications are the main topics of this review. This review attempts to offer insights into the future prospects and breakthroughs in floating microspheres for antidiabetic therapy by a thorough analysis of recent advancements.
There has been a recent rise in the number of patients suffering from chronic illnesses. Therefore, it may be essential to take the medication for a longer amount of time or to take different dosages of the same medication at the same time, which may promote non-compliance. A variety of prolonged action formulations that offer continuous release of the active components at a determined rate and for a determined amount of time fall under the category of controlled release dosage forms.[1] The main goal of oral controlled drug delivery, which is the most effective methodof drug delivery, is to improve the drug's bioavailability and release from the system, which should be predictable and repeatable, simple to administer, patient compliance, and flexible in formulation for efficient therapy. It can also increase the drug's therapeutic efficiency by improving bioavailability. [2] The most prevalent endocrine condition, diabetes mellitus (DM) affects about 100 million people globally. It is brought on by the pancreas' inability to produce enough insulin, which causes variations in blood glucose levels.Diabetes mellitus type 1 and type 2 are caused by autoimmune attacks on the pancreas and insulin resistance, resulting in decreased insulin production. [3]When it comes to treating diabetes, oral medication distribution is still the most common method, particularly for medications like metformin, glipizide, and gliclazide. However, a lot of these medications have poor gastrointestinal absorption, which lowers their bioavailability and effectiveness.
Floating microspheres present a promising method for enhancing the therapeutic results of antidiabetic drugs because of their capacity to regulate drug release and extend the stomach residence period. Because of their reduced density, floating microspheres are a kind of multiparticulate system intended to float on stomach juices. These systems have a prolonged half-life in the stomach, which promotes better absorption, prolonged drug release, and fewer dose intervals. Drugs like antidiabetics, which need constant plasma concentration levels to maintain glycemic control, benefit greatly from floating microspheres. [4]
Gastro Retentive Drug Delivery Systems
This unique method improves medication absorption and boosts therapeutic efficiency by lengthening the period that pharmaceuticals remain in the stomach and increasing gastric residency time. Increased absorption, fewer dosage intervals, less variation in plasma drug concentration, improved therapeutic efficacy and decreased side effects, improved patient compliance, and increased bioavailability are just a few of its benefits.[5]
Approaches of Gastric Retension: There are several approaches to increase gastric retention time of adosage form in stomach. They are as follows:
Floating Systems: These systems can float on gastric fluids and remain in the stomach for an extended period of time due to their low density.
Mucoadhesive Systems: They adheres to the gastric mucosa, which extends their residence time in the stomach.
Swelling Systems:These systems enlarge in the stomach to avoid passageway over the pylorus, sustaining their retention in the stomach.
High-Density Systems: These sink to the bottom of the stomach, where they stay lengthier than conventional forms.[6]
Fig 1: GRDDS Approaches
Floating drug delivery systems (FDDS)
Hydrodynamically balanced system (HBS) is another name for the floating medication delivery system. Davis originally used the term "floating systems" in 1968. FDDS is a kind of gastroretentive drug delivery system that is intended to float for an extended amount of time on the stomach's gastric juices. Because of its floating property, the medication can remain in the stomach for extended periods of time, releasing the active component in a more regulated and prolonged manner. [7]
Floating microspheres
A floating microsphere is a solid, roughly spherical particle with a size range of 1 to 1000 um. One kind of gastroretentive medication delivery device developed using a noneffervescent method is floating microspheres. Floating microspheres are also referred to as hollow microspheres, microballoons, or floating microparticles. Usually, the microspheres are free-flowing powders composed of artificial polymers or proteins that naturally biodegrade. They are intended to float on gastric fluid with a specific density of less than one. This property effects in extended transit over the stomach. Solid biodegradable microspheres with a drug dissolved or dispersed throughout the particle matrix have the potential for controlled release of drugs that remain in the stomach for an extended amount of time. The medication is released gradually at the desired rate, improving gastric retention with less fluctuations in plasma drug concentration.[8]
Fig 2: Floating Microspheres
Advantages of floating microspheres
Because continuous drug release maintains a desired plasma drug concentration and prevents fluctuations in plasma drug concentration, bioavailability increases despite the first pass effect.
Due to the uniform drug release and lack of dose dumping risk associated with microspheres, they are deemed superior than single-unit floating dosage forms.
Improved absorption of medications that only dissolve in the stomach.
It is possible to administer medication to the stomach at a specific site.
Avoiding gastrointestinal distress because of the prolonged release mechanism.
Drugs with a short half-life may have better therapeutic effects. [9]
Mechanism of floatation of microspheres
The gel formers, polysaccharides, and polymers hydrate to form a colloidal gel barrier that regulates the pace of fluid penetration into the device and the ensuing medication release when microspheres interact with gastric fluid. The hydration of the neighboring hydrocolloid layer helps to retain the gel layer when the dosage form's outer surface disintegrates. The air inside the expanded polymer decreases in density, giving the microspheres buoyancy. However, to enable correct buoyancy achievement, a minimal stomach content is required. [10]
Fig 3: Mechanism of floatation of microspheres
Drug release mechanism from the microspheres
The following techniques can be used to release drugs from microspheres
Erosion: Certain coatings have the ability to gradually dissolve over time, releasing the medication that is inside the particle.
Diffusion: Water diffuses into the interior of the particle when it is exposed to aqueous fluids in the GIT. Drug solutions distribute across the release coat and onto the outside as drug disintegration takes place.
Osmosis: A particle's interior can develop an osmotic pressure if water is permitted to enter under the correct circumstances. Via the coating, the medication is pushed from the particle and onto the outside.[11]
Polymers used in floating microspheres
Polymers are essential for the creation of floating microspheres because they offer the required characteristics such stability, buoyancy, and controlled medication release. Sodium Alginate, Chitosan, PCL, Carbopol, Ethylcellulose, PVA, Eudragit, PLGA, Gelatin, Xanthan Gum, HEC, PVP, Methylcellulose, Gellan Gum, etc.[12]
Antidiabetic drugs used in floating microspheres
Metformin : The first-line oral antidiabetic medication for type 2 diabetes is metformin.It functions by raising insulin sensitivity and reducing the amount of glucose produced by the liver. Metformin has better absorption and solubility in the upper gastrointestinal tract when it is synthesized into floating microspheres. It also has a controlled release profile that can lower dosage frequency and increase patient compliance.
Glibenclamide :glibenclamide is a sulfonylurea that motivates insulin secretion, gains from a prolonged release when added to microspheres that float. By lowering peak medication concentrations, this not only helps to maintain stable blood glucose levels but also reduces the risk of hypoglycemia.
Gliclazide : Another sulfonylurea that is frequently used to treat type 2 diabetes is gliclazide. Gliclazide floating microspheres have been demonstrated to reduce blood glucose variations by delivering a more regulated medication release.
Sitagliptin : The DPP-4 inhibitor sitagliptin, which raises incretin levels, also gains from floating microsphere technology. The drug's pharmacokinetic profile and bioavailability are improved by this formulation's capacity to release the medication steadily, which is especially helpful for patients whose absorption is inconsistent.
Pioglitazone : It improves insulin sensitivity and controls glucose metabolism. Because of its floating microsphere formulation, which enhances stomach retention and absorption in the gastrointestinal tract, blood glucose swings are more steadily controlled over an extended period of time. [13]
Formulation Techniques for floating Microspheres:
The floating microspheres are prepared using the following techniques.
Solvent EvaporationMethod: Using an organic solvent extraction process, the organic phase is eliminated in this microparticle preparation approach. The microspheres' hardening time is shortened by the procedure. Direct addition of the medication is one method variant. The water's temperature, the emulsion volume to water ratio, and the polymer's solubility profile all affect how quickly solvent is removed from a solution. [14]
Fig 4: Solvent EvaporationMethod
Spray Drying:The polymer must first dissolve in an appropriate volatile organic solvent before using the spray drying process. Next, using high-speed homogenization, the medication in its solid form is distributed throughout the polymer solution. A hot air stream is then used to atomize this dispersion. Small droplets or fine mist are formed as a result of atomization, and when the solvent instantly evaporates, microspheres with sizes between one and 100 μm are formed.[15]
Fig 5: Spray Drying
Ionic gelation method:The method involves dispersing cross-linking agents and polymers in purified water to create a homogeneous polymer mixture. The drug is added to the polymer and mixed thoroughly. A gelation medium is prepared by dissolving calcium chloride in glacial acetic acid. The homogenous alginate solution is extruded, and the microspheres are collected, washed, and dried for 24 hours.[16]
Fig 6: Ionotropic gelation
Wax Coating and Hot Melt:To create the microspheres, the polymer is dissolved in an appropriate dispersion medium and chilled gradually. This technology makes it easy to synthesize low melting point polymers into microspheres. The most common coatingingredients are beeswax and carnauba wax, which can be combined to produce the required properties.[17]
Characterization of Floating Microspheres
Characterization of floating microspheres is an significant phenomenon which supports in the estimation of suitable drug delivery systems. Floating microspheres are categorized by following parameters:
Particle size: Using an optical microscopic technique, the microspheres' particle sizes were determined, and the mean microsphere size was determined by counting 100 particles using an ocular micromter that had been calibrated. [18]
Bulk density:The mass of the powder divided by the bulk volume is known as bulk density. precisely weighed ten grams A 25 milliliter measuring cylinder was filled with a sample of granules. Without moving the cylinder, the volume occupied by the granules was measured, and bulk density was computed using the following formula.[19]
Bulk density = Weight of Sample/ Volume of Sample
Tapped density:Tapped densities can be computed by the tapping method. Using a tapped density device, the volume of the weighed quantity of microspheres was calculated after 100 and 1000 taps.[20]
Tapped density = Weight of Sample/ Tapped Volume
Compressibility Index and Hausner Ratio:Using the following calculations, the compressibility index and hausner ratio were determined from the bulk density and tapped density values:
Compressibility Index = (Tapped density-Bulk density)/Tapped Density × 100
Hausner ratio =Tapped Density/ Bulk Density
Angle of Repose:The microspheres' angle of repose (σ), which gauges their resistance to particle flow, was computed as? = Tan-1 h/r
Where r is the pile's radius, h is its height, and σ is its angle of repose.
Percentage yield: This is computed by dividing the actual weight of product by the total amount of all nonvolatile components that are used in the preparation of floating microspheres. [21]
% yield = actual weight of floating microsphere / total weight of excipient and drug * 100
Surface morphology:Scanning electron microscopy is used to analyze the surface features of floating microspheres. Before observation, samples are vacuum-coated with gold dust. To view the microspheres' interior structure and core, cross sections must be created. These studies are important in the assessment of internal and exterior morphology of floating microspheres. [22]
Swelling ratioTo investigate the swelling property of floating microspheres, immerse a known weight of microspheres in 0.1 N HCl or phosphate buffer pH 6.8 for the necessary amount of time in a glass beaker at 37 ± 0.5°C. The microspheres are taken out at various times after being given opportunity to inflate. [23]
Buoyancy studiesBy dispersing floating microspheres over simulated stomach fluid with surfactant, in vitro floating tests can be carried out using USP type II dissolving test equipment. At 100 revolutions per minute, the medium is agitated to ascertain the floating microspheres' buoyancy. [24]
Buoyancy % = Qf / Qf + Qs * 100
Where, Qf and Qs are the masses of floating and settled hollow microspheres, respectively.
In vitro drug release studiesThe drug release rate from hollow floating microspheres is determined using a USP dissolution apparatus at 37± 0.5°C. The test uses 900 mL of 0.1 N HCl dissolution medium at 100 rpm. Sample solutions are filtered and analyzed using a UV spectrophotometer. The medium is maintained by reintroducing new aliquots at intervals. [25]
Applications of floating microspheres of antidiabetic drugs
Regulats Drug release
Sustains stable blood glucose levels.
Improved absorption in the gastrointestinal tract.
Release at targeted sites in the GI tract.
Decrease of Gastrointestinal Side Effects.
Higher Patient Compliance
Defends drugs from environmental degradation.
Combination Therapy
The possibility of synergistic effects.
Less Fluctuations in Blood Sugar Levels.
CONCLUSION
Floating microspheres offer a potential development in antidiabetic drug delivery methods, successfully resolving the issues of bioavailability and stomach retention. These formulations have the potential to greatly increase therapeutic results and patient compliance by improving the solubility and extending the release of medications including metformin, glibenclamide, pioglitazone, acarbose, and sitagliptin. The clinical significance of floating microspheres in the therapy of diabetes is highlighted by their capacity to maintain stable blood glucose levels while reducing adverse effects like hypoglycemia. There may be more widespread uses for these microspheres in the treatment of diabetes and other chronic illnesses as research into their formulation methods and qualities proceeds. In the end, using floating microsphere technology in clinical settings may result in therapeutic approaches that are both more patient-friendly and successful, which would have a big influence on diabetes management as a whole.
REFERENCES
Sahil K, Akanksha M, Premjeet S, Bilandi A, Kapoor B. Microsphere: A review. Int. J. Res. Pharm. Chem. 2011; 1(4):1184- 98.
Virmani T, Gupta J. Pharmaceutical application of microspheres: an approach for the treatment of various diseases. Int J Pharm Sci Res. 2017; 8(8):3253-60.
Patel NR, Patel DA, Bharadia PD, Pandya V, Modi D. Microsphere as a novel drug delivery. International Journal of Pharmacy & Life Sciences. 2011 Aug 1; 2(8):2334-2345.
Prasad BS, Gupta VR, Devanna N, Jayasurya K. Microspheres as drug delivery system-a review. J Glob Trends Pharm Sci. 2014; 5(3):1961-72.
Mukund JY, Kantilal BR, Sudhakar RN. Floating microspheres: a review. Brazilian Journal of Pharmaceutical Sciences. 2012; 48:17-30.
Kawatra M, Jain U, Ramana J. Recent advances in floating microspheres as gastro-retentive drug delivery system: A review. Int J Recent Adv Pharm Res. 2012; 2(3):5-23.
Rastogi V, Shukla SS, Singh R, Lal N, Yadav P. Microspheres: a promising drug carrier. Journal of Drug Delivery and Therapeutics. 2016 May 15; 6(3):18-26.
Kumar A, Mahajan S, & Bhandari N. Microspheres: a review. World J Pharm Sci. 2017; 14(6):724-40.
Dutta P, Sruti J, Niranajan P, Bhanoji MER. Floating Microspheres: Recent trends in the development of gastroretentive floating drug delivery system. Int J of Pharm Sci and Nanotech. 2011; 4(1): 1296-1306.
Faraz J, Sunil K, Saurabh S, Prabhakar V, Lalit S. Review on stomach specific drug delivery systems: Development and Evaluation. Int J of Res in Pharm and Biomed Sci. 2011; 2(4):1427-33.
Jagtap YM, Bhujbal RK, Ranpise NS. Floating microspheres: A Review. Braz J Pharm Sci. 2012; 48(1):18-30.
Manjusha AG, Archana KG. A Review on Floating Microspheres as Gastroretentive Drug Delivery System. Am. J. Pharm Health Res. 2013; 1(9):2-21.
Abhishek C, Kapil C, Bharat P, Hitesh K, Sonia A. Floating drug delivery systems: A better approach. Int Curr Pharm J. 2012; 1(5):110-18.
Mayavanshi AV, Gajjar SS. Floating drug delivery systems to increase gastric retention of drugs: A Review. Res J of Phar and Tech. 2008; 1(4):345-48.
Sharma S, Pawar A. Low density multiparticulate system for pulsatile release of meloxicam. Int J Pharm. 2006; 313:150-58.
Deshpande AA, Shah NH, Rhodes CT, Malik W. Development of a novel controlled release system for gastric retention. Pharm. Res. 1997; 14(1):815-19.
Rajput S, Agrawal P, Pathak A, Shrivasatava N, Baghel SS, Baghel RS. A review on microspheres: methods of preparation and evaluation. World journal of pharmacy and pharmaceutical sciences. 2012; 1:422-38.
Saini S, Kumar S, Choudhary M, Nitesh, Budhwar V. Microspheres as controlled drug delivery system: an updated review. International journal of pharmaceutical sciences and research. 2018; 9(5):1760-8.
Patel KS, Patel MB. Preparation and evaluation of chitosan microspheres containing nicorandil. International journal of pharmaceutical investigation. 2014; 4(1):32.
Kadam N. R. and Suvarna V, Microspheres: A Brief Review. Asian Journal of Biomedical and Pharmaceutical Sciences. 2015; 3(4):13-15.
Gurung BD, Kakar S. An overview on microspheres. Int J Health Clin Res. 2020; 3(1):11-24.
Lachman LA, Liberman HA, Kanig JL. The Theory and Practice of Industrial Pharmacy. Varghese Publishing House, Mumbai, India. 1991, 3:414-415.
Bansal H, Kaur SP, Gupta AK. Microspheres: methods of preparation and applications: A comparative study. Int J Pharm Sci Rev Res. 2011; 10(1):69-78.
Suvarna V. Microspheres: a brief review. Asian Journal of Biomedical and Pharmaceutical Sciences. 2015; 5(47):13-19.
Yadav R, Bhowmick M, Rathi V, Rathi J. Design and characterization of floating microspheres for rheumatoid arthritis. Journal of Drug Delivery and Therapeutics. 2019; 9(2):76-81
Reference
Sahil K, Akanksha M, Premjeet S, Bilandi A, Kapoor B. Microsphere: A review. Int. J. Res. Pharm. Chem. 2011; 1(4):1184- 98.
Virmani T, Gupta J. Pharmaceutical application of microspheres: an approach for the treatment of various diseases. Int J Pharm Sci Res. 2017; 8(8):3253-60.
Patel NR, Patel DA, Bharadia PD, Pandya V, Modi D. Microsphere as a novel drug delivery. International Journal of Pharmacy & Life Sciences. 2011 Aug 1; 2(8):2334-2345.
Prasad BS, Gupta VR, Devanna N, Jayasurya K. Microspheres as drug delivery system-a review. J Glob Trends Pharm Sci. 2014; 5(3):1961-72.
Mukund JY, Kantilal BR, Sudhakar RN. Floating microspheres: a review. Brazilian Journal of Pharmaceutical Sciences. 2012; 48:17-30.
Kawatra M, Jain U, Ramana J. Recent advances in floating microspheres as gastro-retentive drug delivery system: A review. Int J Recent Adv Pharm Res. 2012; 2(3):5-23.
Rastogi V, Shukla SS, Singh R, Lal N, Yadav P. Microspheres: a promising drug carrier. Journal of Drug Delivery and Therapeutics. 2016 May 15; 6(3):18-26.
Kumar A, Mahajan S, & Bhandari N. Microspheres: a review. World J Pharm Sci. 2017; 14(6):724-40.
Dutta P, Sruti J, Niranajan P, Bhanoji MER. Floating Microspheres: Recent trends in the development of gastroretentive floating drug delivery system. Int J of Pharm Sci and Nanotech. 2011; 4(1): 1296-1306.
Faraz J, Sunil K, Saurabh S, Prabhakar V, Lalit S. Review on stomach specific drug delivery systems: Development and Evaluation. Int J of Res in Pharm and Biomed Sci. 2011; 2(4):1427-33.
Jagtap YM, Bhujbal RK, Ranpise NS. Floating microspheres: A Review. Braz J Pharm Sci. 2012; 48(1):18-30.
Manjusha AG, Archana KG. A Review on Floating Microspheres as Gastroretentive Drug Delivery System. Am. J. Pharm Health Res. 2013; 1(9):2-21.
Abhishek C, Kapil C, Bharat P, Hitesh K, Sonia A. Floating drug delivery systems: A better approach. Int Curr Pharm J. 2012; 1(5):110-18.
Mayavanshi AV, Gajjar SS. Floating drug delivery systems to increase gastric retention of drugs: A Review. Res J of Phar and Tech. 2008; 1(4):345-48.
Sharma S, Pawar A. Low density multiparticulate system for pulsatile release of meloxicam. Int J Pharm. 2006; 313:150-58.
Deshpande AA, Shah NH, Rhodes CT, Malik W. Development of a novel controlled release system for gastric retention. Pharm. Res. 1997; 14(1):815-19.
Rajput S, Agrawal P, Pathak A, Shrivasatava N, Baghel SS, Baghel RS. A review on microspheres: methods of preparation and evaluation. World journal of pharmacy and pharmaceutical sciences. 2012; 1:422-38.
Saini S, Kumar S, Choudhary M, Nitesh, Budhwar V. Microspheres as controlled drug delivery system: an updated review. International journal of pharmaceutical sciences and research. 2018; 9(5):1760-8.
Patel KS, Patel MB. Preparation and evaluation of chitosan microspheres containing nicorandil. International journal of pharmaceutical investigation. 2014; 4(1):32.
Kadam N. R. and Suvarna V, Microspheres: A Brief Review. Asian Journal of Biomedical and Pharmaceutical Sciences. 2015; 3(4):13-15.
Gurung BD, Kakar S. An overview on microspheres. Int J Health Clin Res. 2020; 3(1):11-24.
Lachman LA, Liberman HA, Kanig JL. The Theory and Practice of Industrial Pharmacy. Varghese Publishing House, Mumbai, India. 1991, 3:414-415.
Bansal H, Kaur SP, Gupta AK. Microspheres: methods of preparation and applications: A comparative study. Int J Pharm Sci Rev Res. 2011; 10(1):69-78.
Suvarna V. Microspheres: a brief review. Asian Journal of Biomedical and Pharmaceutical Sciences. 2015; 5(47):13-19.
Yadav R, Bhowmick M, Rathi V, Rathi J. Design and characterization of floating microspheres for rheumatoid arthritis. Journal of Drug Delivery and Therapeutics. 2019; 9(2):76-81
Janhavi Chaudhari*, Dr. Prashant Malpure, Rahul Arote, Dr. Gokul Talele, Floating Microspheres in Diabetes Treatment: A Comprehensive Review, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 3, 1709-1717. https://doi.org/10.5281/zenodo.15046943
10.5281/zenodo.15046943
