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Year : 2014  |  Volume : 5  |  Issue : 1  |  Page : 1-10  

Hollow microspheres as a drug carrier: An overview of fabrication and in vivo characterization techniques

University Institute of Pharmacy, Pandit Ravishankar Shukla University, Raipur, Chhattisgarh, India

Date of Web Publication25-Mar-2014

Correspondence Address:
Preeti Kumaran Suresh
University Institute of Pharmacy, Pandit Ravishankar Shukla University, Raipur - 492 010, Chhattisgarh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2229-5186.129327

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Oral controlled release dosage forms encounter several physiological constraints like inability to retain and locate the controlled drug delivery system within the desired region of the gastrointestinal tract (GIT) due to variation in gastric emptying. This leads to non - uniform absorption profile, insufficient drug release and shorter residence time of the dosage form in the stomach. As the fallout of this event, there is incomplete absorption of the drug having absorption window especially, in the upper part of GIT. These considerations have led to the development of oral controlled release dosage forms with gastroretentive properties. Hollow microspheres hold promise as one of the potential approaches for gastric retention. Hollow microspheres are spherical empty particles without core and can remain in the gastric region for prolonged periods. They significantly extend the gastric residence time of drugs, thereby improving bioavailability, reduced the drug waste and improved solubility for drugs that are less soluble at a higher pH environment. This review attempts to bring more insight into recent advances in methods of fabrication techniques and applications of hollow microspheres.

Keywords: Controlled release, floating microspheres, gastric retention, hollow microspheres, low density, oral

How to cite this article:
Kurrey A, Suresh PK, Singh MR. Hollow microspheres as a drug carrier: An overview of fabrication and in vivo characterization techniques. Chron Young Sci 2014;5:1-10

How to cite this URL:
Kurrey A, Suresh PK, Singh MR. Hollow microspheres as a drug carrier: An overview of fabrication and in vivo characterization techniques. Chron Young Sci [serial online] 2014 [cited 2020 Jan 27];5:1-10. Available from:

   Introduction Top

The oral route is the most acceptable mode for the administration of pharmacologically active substance to the systemic circulation. Some drugs have ideal characteristics for good absorption throughout the gastrointestinal tract (GIT), whereas others have difficulties. [1] To achieve the effective oral drug delivery, oral controlled release dosage form have been developed over many decades. They offer considerable therapeutic advantages in terms of ease of administration, reduced dosing frequency, better patient compliance and flexibility in formulation. [2] However, in this approach several physiological difficulties have been encountered due to inability to retain and locate the controlled drug delivery system within the desired region of GIT. These problems are manifested due to variation in gastric emptying, leading to non-uniform absorption profile, insufficient drug release and shorter residence time of the dosage form in the stomach. [3] This leads to incomplete absorption of the drug having absorption window, especially in the upper part of GIT. [4] These considerations have led to the development of oral controlled release dosage form with gastroretentive properties.

The ability of gastroretentive systems to remain in the gastric region for a longer period significantly prolong the gastric retention time of drugs. Improved bioavailability, reduction in drug waste and improvement in solubility of drugs that have limited solubility in high pH environment can be achieved by prolonging gastric retention of drugs. [5],[6]

   Approaches to Gastric Retention Top

Various approaches have been reported to achieve gastric retention of an oral dosage form. These include.

Hydrodynamically balanced systems

In hydrodynamically balanced systems, drug with gel-forming hydrocolloids are meant to remain buoyant over the stomach content. This prolongs gastric retention time and maximizes the amount of drug that reaches its absorption sites. These hydrocolloids on contact with gastric fluid, hydrates and forms a colloid gel barrier around its surface. [7]

Effervescent systems

The gas generating agents such as carbonates (e.g., sodium bicarbonate) and other organic acid (e.g., citric acid and tartaric acid) are utilized in the formation effervescent systems. The density of the present system is reduced due to the production of carbon dioxide by the reaction of gas generating agents with gastric acid, thus allowing the system to float on the gastric fluid. [8]

Low-density systems

Floating systems are based on low density approach. Floating drug delivery systems by virtue of their bulk density lower than gastric fluids (<1 g/ml), float over the gastric fluid and release the drug slowly for a longer period of time. They are prepared by incorporating low-density materials, entrapping oil or air. Most are multiple unit systems and are also called "microballoons" because of their low-density core. [9]

Raft systems

Raft systems upon contact with gastric fluid form a viscous cohesive gel, which swells to form a continuous layer called a raft. Generation of CO 2 by a gel forming solution (e.g. sodium alginate solution containing carbonates or bicarbonates) makes the raft float on gastric fluid. [10]

Bioadhesive or mucoadhesive systems

Bioadhesive systems bind to the gastric epithelial cell surface and extend the residence time of the dosage form in the stomach, thereby facilitating an intimate contact of drug with the biological membrane for prolonged duration. This approach involves the use of bioadhesive polymers such as polycarbophil, carbopol, lectins, chitosan and gliadin. [11]

High-density systems

High-density systems have a density (3 g/ml) far exceeding that of normal stomach contents (1 g/ml) and are thus retained in the fold of the stomach for a longer period of time. This is achieved by coating the drug with heavy inert materials such as barium sulfate, zinc oxide, titanium dioxide, iron powder, etc. [12]

   Hollow Microspheres Top

Hollow microspheres are gastroretentive drug delivery systems based on non-effervescent approach. They are spherical empty particles without core. They possess the unique advantages of multiple unit systems and their center hollow space imparts good floating properties making them promising buoyant systems. These microspheres are free flowing low density powders, having a size less than 200 μm, comprising of either proteins or synthetic polymers. [13] The sustained release of drug from the buoyant systems improves the gastric retention and reduces the fluctuations in plasma drug concentration. [14] The quantity of polymers, the plasticizer-polymer ratio and the solvent used for formulation modulates buoyancy and drug release from the dosage form. Commonly used polymers to develop hollow microspheres include polycarbonate, HPMC, cellulose acetate, calcium alginate, Eudragit S, chitosan and low methoxylated pectin. Several investigations have shown that the hollow microspheres are capable of floating continuously over the surface of an acidic dissolution media containing surfactant for >12 h. [9] [Figure 1] is a schematic representation of the floating microspheres.
Figure 1: Schematic representation of floating microspheres

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Hollow microspheres offer various advantages including:

  1. Improves patient compliance by reducing dosing frequency. [15]
  2. Enhanced bioavailability despite the first-pass effect because fluctuations in plasma drug concentration is avoided; a desirable plasma drug concentration is maintained by continuous drug release. [15]
  3. Increased gastric retention time due to buoyancy. [16]
  4. Enhanced absorption of drugs, which solubilize only in the stomach. [17]
  5. Controlled drug release for a prolonged period. [16]
  6. Site-specific drug delivery to stomach can be achieved. [16]
  7. Avoidance of gastric irritation due to sustained release effect. [17]
  8. Better therapeutic effect of short half-life drugs can be achieved. [18]


Although hollow microspheres have a number of potential advantages, their use can be limited due to the following:

  1. High level of fluids in the stomach is required for the hollow microspheres to float and work efficiently. [4]
  2. The dosage form should be administered with a full glass of water (200-250 ml). [19]
  3. Not suitable for drugs having solubility or stability problem in gastric fluids. [19]
  4. The drugs that undergo first-pass metabolism (nifedipine, propranolol, etc.) are not suitable candidates. [5]
  5. Irritant drugs to the gastric mucosa are not suitable for gastroretentive systems. [19]

   Techniques for Preparation of Hollow Microspheres Top

Various methods have been developed for the preparation of hollow microspheres. These include solvent evaporation, emulsion solvent diffusion, spray drying and miscellaneous methods. These techniques are discussed in detail in the following section.

Solvent evaporation method

Solvent evaporation technique is widely employed to obtain the controlled release of drug. In this method, the drug and polymer are dissolved in an organic phase (usually methylene chloride) and dispersed in an excess amount of aqueous continuous phase, with the aid of an agitator to form an emulsion [Figure 2]. Depending upon the hydrophilicity or the hydrophobicity of drugs, different methods are used to prepare microspheres by solvent evaporation technique [Table 1]. The oil-in-water method is frequently utilized for insoluble or poorly water-soluble drugs, whereas for hydrophilic drugs, this method is inappropriate due to dissolution and extensive loss of drug. Hence, for incorporation of hydrophilic drugs water in oil in water double emulsion method, oil in water co-solvent method and oil in oil non-aqueous solvent evaporation method can be employed. [20]
Figure 2: Schematic representation of solvent evaporation method

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Table 1: Various hollow microspheres prepared by solvent evaporation method

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Solvent evaporation is the simplest method for fabrication of microspheres where process can be controlled easily and the formed microspheres show good product yield and high encapsulation efficiency. [21] However, the limitation remains that the rate of solvent removal may affect the physicochemical properties of formed hollow microspheres and it requires additional processing for removal of residual solvent. [Table 1] lists the various hollow microspheres prepared by this method.

Emulsion solvent diffusion method

Kawashima et al. proposed hollow microspheres (so-called "microballoons") prepared by novel emulsion solvent diffusion method based on enteric acrylic polymers containing the drug in the polymeric shell. [9],[40] The preparation method and mechanism of microballoon formation is schematically illustrated in [Figure 3]. Typically, the method involves dispersion of solution of polymer and drug in a mixture of dichloromethane and ethanol into an agitated aqueous solution of surfactants. The ethanol rapidly partitions into the external aqueous phase and the polymer precipitates around dichloromethane droplets. The subsequent evaporation of the entrapped dichloromethane leads to the formation of internal cavities within the microspheres. [40],[41] The major advantages of emulsion solvent diffusion method include uniform and narrow size distribution of formed microspheres and the high efficiency of the process. However, it is relatively complex process, which cannot be controlled easily. [Table 2] summarizes the various drugs entrapped by this method.
Figure 3: Schematic illustration of hollow microsphere formation by emulsion solvent diffusion method

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Table 2: Various hollow microspheres prepared by emulsion solvent diffusion method

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Spray drying

Spray drying is the most widely employed industrial process for particle formation and drying. It is an ideal process where the required particle size distribution, bulk density and particle shape can be obtained in a single step. [68]

In this technique polymer is first dissolved in a suitable volatile organic solvent (e.g., dichloromethane, acetone) to form a slurry. The slurry is then sprayed into the drying chamber, concentration gradient of the solute forms inside the small droplet with the highest concentration being at the droplet surface. This is because the time of the solute diffusion is longer than that of the solvent in the droplets evaporating during the drying process. Subsequently, a solid shell appears leading to the formation of microspheres. Separation of the solid products from the gases is usually accomplished by means of a cyclone separator while the traces of solvent are removed by vacuum drying and the products are saved for later use [69] [Figure 4].
Figure 4: Schematic presentation of spray drying method

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Spray drying method has advantages of being an easily controlled simple process with ease of scale-up. In addition, narrow particle size distribution and required particle size can be obtained in a single step. The limitations include that the product morphology is affected by various processing variables and the high cost of the process. [Table 3] presents the various hollow microspheres prepared by spray drying method.
Table 3: Various hollow microspheres prepared by spray drying method

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Apart from the above mentioned techniques, several modifications in the fabrication of hollow microspheres have been attempted to achieve the various objectives. Some of these approaches are summarized in [Table 4].
Table 4: Hollow microspheres prepared by miscellaneous techniques

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   In vivo Profiling of Hollow Microspheres Top

In vivo investigations are an integral part for the evaluation of hollow microspheres. Some of these studies are discussed in the following section and summarized in [Table 5].
Table 5: In-vivo evaluations of hollow microspheres

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Gamma scintigraphy

Gamma scintigraphy has become one of the most popular method to investigate the gastrointestinal performance of the product. [84] Gamma scintigraphy is a technique by which the transit of a dosage form through its intended site of delivery can be noninvasively imaged in vivo by the introduction of a radiolabelled drug formulation. The gamma radiations emitted by the incorporated radionuclide with energies between 100 and 250 KeV are captured by external detectors such as gamma cameras coupled to a sophisticated data processing system and used to quantify the formulation in vivo. [85] Radiopharmaceuticals labeled with (99 mTc) technetium are most commonly used, however, other sources of radionuclides such as (111In) indium, (175Yb) ytterbium, (68Sm) Samarium, etc., can also be employed. [86] The prime advantages of gamma scintigraphy include modest radiation exposure to the participating subjects compared with roentgenography (i.e., X-ray methods), both qualitative and quantitative observations can be recorded that are not feasible with other techniques. It also offers total non-invasiveness and in vivo evaluation of dosage forms is possible under normal physiological conditions.


Radiography has been used for many years for the assessment of gastric transit of dosage forms throughout the GIT. It involves the inclusion of a radio-opaque material into an oral drug delivery system to evaluate its in vivo behavior by radiological procedures. [87] Its major advantages over gamma scintigraphy are the simplicity and cost. However, the major drawbacks are repeated exposure to X-rays, necessity to modify the physical state of the dosage form in order to make it radioopaque and qualitative nature of the data collected. A commonly used contrast agent for radiography is barium sulphate. [88]


Ultrasonic imaging can be employed for visualizing internal body structures. An ultrasonic image is formed when beam of very high frequency sound impulse (1.5-10 MHz) is sent into a subject and is reflected back to a varying degree depending upon the density of the medium through which it is passing. [84] It is a noninvasive and safe technique. [89] Most of the dosage forms do not have sharp acoustic mismatches across their interface with the physiological milieu, thereby limiting the use of ultrasonography for the evaluation of floating drug delivery systems. The characterization includes assessment of intragastric location of the hydrogels and interactions between gastric wall and floating microspheres during peristalsis.

Alternating current biosusceptometry

Alternate current biosusceptometry (ACB) is an innovative, non-invasive and radiation free biomagnetic technique used to evaluate floating systems in the GIT. In this technique, variation of magnetic flux from an ingested magnetic material is recorded by a set of induction coils. The material (ferrites like MgFe 2 O 3 ) does not need to be premagnetized as it is continuously magnetized by an alternating field with a frequency of 10 kHz and a magnetic field of 20G generated by the excitation coils. [90] The magnetic signals detected by the ACB sensors depend on the surface area of the detection coil, number of turns, rate of change of the magnetic flux, amount of ferromagnetic material and distance among the sensors. [91]

Magnetic resonance imaging

Magnetic resonance imaging is a noninvasive imaging technique that is based on the principle of nuclear magnetic resonance. The high spatial resolution in combination with very good contrast resolution makes MRI an admirable tool in gastrointestinal research for the analysis of gastric emptying, motility and intra gastric distribution of macronutrients and drug models. The advantages of MRI include avoidance of ionization radiation, excellent anatomical imaging, high scan volumes and use of harmless MR imaging contrast agents. However, the magnetic resonance imaging encounters the problems of acquisition time and the signal to noise ratio. In order to solve these problems different strategies can be followed. [91] Use of either paramagnetic or ferromagnetic contrast agents (ferromagnetic iron oxides) for the labeling of the delivery system is very common. A combination of materials with very different contrast properties can also be used to specifically enhance or suppress signal of fluids and tissues of interest and thus permit better delineation and study of organs. [92]

[Table 5] enlists the various in vivo investigations performed with hollow microspheres.

   Conclusion Top

The process of gastrointestinal drug absorption is highly variable. Among the drugs currently in clinical use are several narrow absorption window drugs. Drugs that possess a narrow absorption window in the upper parts of the gastrointestinal tract are ideal candidates for a gastroretentive drug delivery system as prolonging gastric retention of the dosage form extends the time for the drug absorption. In spite of extensive research conducted to develop controlled or sustained release delivery systems, very few systems have been developed, which are retained in the stomach for a long time.

A wide variety of active agents of different therapeutic functions such as anti-inflammatory, antibiotics, anti-ulcer, anti-diabetic, have been formulated into hollow microspheres with promising in vitro and in vivo results. Hollow microspheres are expected to provide an economical, safe and more bioavailable formulation for the effective management of diverse diseases. Some of the hollow microsphere-related patents have been listed in [Table 6].
Table 6: Patents for some hollow microspheres based gastroretentive drug delivery systems

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It is expected that extension of applications of imaging techniques and recently developed methods may yield a deeper insight into the mechanisms of gastroretentivity. This will ensure the successful advancements in the area of gastroretentive microspheres therapy so as to optimize the delivery of molecules in a more efficient manner. Furthermore, recent innovations in pharmaceutical investigation will surely provide real prospects for the establishment of novel and effective means in the development of this promising drug delivery system.[102]

   References Top

1.Davis SS. Formulation strategies for absorption windows. Drug Discov Today 2005;10:249-57.  Back to cited text no. 1
2.Streubel A, Siepmann J, Bodmeier R. Drug delivery to the upper small intestine window using gastroretentive technologies. Curr Opin Pharmacol 2006;6:501-8.  Back to cited text no. 2
3.Garg R, Gupta GD. Progress in controlled gastroretentive systems. Trop J Pharm Res 2008;7:1055-66.  Back to cited text no. 3
4.Rouge N, Buri P, Doelke E. Drug absorption sites in the gastrointestinal tract and dosage forms for site specific delivery. Int J Pharm 1996;136:117-39.  Back to cited text no. 4
5.Arora S, Ali J, Ahuja A, Khar RK, Baboota S. Floating drug delivery systems: A review. AAPS PharmSciTech 2005;6:E372-90.  Back to cited text no. 5
6.Chein YW. Novel Drug Delivery System. 2 nd ed. New York: Marcel Dekker Inc.; 1992.  Back to cited text no. 6
7.Seth PR, Tossounian J. The hydrodynamically balanced system, a novel drug delivery system for oral use. Drug Dev Ind Pharm 1984;10:313-39.  Back to cited text no. 7
8.Vinod KR, Vasa S, Anbuazaghan S, David B, Padmasri A, Sandhya S. Approaches for gastroretentive drug delivery systems. Int J Appl Biol Pharm Technol 2010;1:589-601.  Back to cited text no. 8
9.Kawashima Y, Niwa T, Takeuchi H, Hino T, Itoh Y. Hollow microspheres for use as a floating controlled drug delivery system in the stomach. J Pharm Sci 1992;81:135-40.  Back to cited text no. 9
10.Deshpande AA, Shah NH, Rhodes CT, Malick W. Development of a novel controlled-release system for gastric retention. Pharm Res 1997;14:815-9.  Back to cited text no. 10
11.Washington N. Investigation into the barrier action of an alginate gastric reflux suppressant. Liquid gaviscon. Drug Investig 1987;2:23-30.  Back to cited text no. 11
12.Dehghan M, Khan FN. Gastroretentive drug delivery systems: A patent perspective. Int J Health Res 2009;2:23-44.   Back to cited text no. 12
13.Vyas SP, Khar RK. Targeted and Controlled Drug Delivery Novel Carrier System. New Delhi: CBS Publishers and Distributors; 2002. p. 417-54.  Back to cited text no. 13
14.Gholap SB, Banarjee SK, Gaikwad DD, Jadhav SL, Thorat RM. Hollow microspheres: A review. Int J Pharm Sci Rev Res 2010;1:74-9.  Back to cited text no. 14
15.Hoffman A, Stepensky D, Lavy E, Eyal S, Klausner E, Friedman M. Pharmacokinetic and pharmacodynamic aspects of gastroretentive dosage forms. Int J Pharm 2004;277:141-53.  Back to cited text no. 15
16.Gaba P, Gaba M, Garg R, Gupta GD. Floating microspheres: A review, 2008. Available from: [Accessed on 31 st January 2012].  Back to cited text no. 16
17.Mathur P, Saroha K, Navneet SN, Verma S, Kumar V. Floating drug delivery system: An innovative acceptable approach in gastroretentive drug delivery. Sch Res Libr 2010;2:257-70.  Back to cited text no. 17
18.Somwanshi SB, Dolas RT, Nikam VK, Gaware VM, Kotadde KB, Dhamak KB, et al. Floating multiparticulate oral sustained release drug delivery system. J Chem Pharm Res 2011;3:536-47.  Back to cited text no. 18
19.Mathur P, Saroha K, Syan N, Verma S, Kumar V. Floating drug delivery system: An innovative acceptable approach in gastroretentive drug delivery. Arch Appl Sci Res 2010;2:257-70.  Back to cited text no. 19
20.Li M, Rouaud O, Poncelet D. Microencapsulation by solvent evaporation: State of the art for process engineering approaches. Int J Pharm 2008;363:26-39.  Back to cited text no. 20
21.Rawat M, Saraf S, Saraf S. Influence of selected formulation variables on the preparation of enzyme-entrapped Eudragit S100 microspheres. AAPS PharmSciTech 2007;8:E116.  Back to cited text no. 21
22.Goswami N, Joshi G, Sawant K. Floating microspheres of valacyclovir HCl: Formulation, optimization, characterization, in vitro and in vivo floatability studies. J Pharm Bioallied Sci 2012;4:S8-9.  Back to cited text no. 22
23.Gadad A, Naval C, Patel K, Dandagi P, Mastiholimath V. Formulation and evaluation of floating microspheres of captopril for prolonged gastric residence time. Indian J Nov Drug Deliv 2011;3:17-23.  Back to cited text no. 23
24.Tanvi R, Diwan A. Novel polymeric combinations for gastroretentive microspheres of stavudine. Int J Drug Dev Res 2011;3:211-6.  Back to cited text no. 24
25.Yadav A, Jain DK. Gastroretentive microballoons of metformin: Formulation development and characterization. J Adv Pharm Technol Res 2011;2:51-5.  Back to cited text no. 25
26.Rajyalakshmi D, Ramareddy J, Rajalakshmi G, Damodharan N. Formulation and evaluation of floating microspheres of metformin hydrochloride. Available at:, 0 [Accessed on 5 th March 2012].  Back to cited text no. 26
27.Fartyal S, Jha SK, Karchuli MS, Gupta R, Vajpayee A. Formulation and evaluation of floating microspheres of boswellic acid. Int J PharmTech Res 2011;3:76-81.  Back to cited text no. 27
28.Kumar DB, Sundaramoorthy K, Vetrichelvan T. Formulation and in vitro evaluation of gastroretentive floating microspheres of ranitidine hydrochloride. Res J Pharm Biol Chem Sci 2011;2:789-801.  Back to cited text no. 28
29.Kavitha K, Mehaboob Y, Ashvini V, Sandeep DS. Formulation and in vitro evaluation of floating microbaloons of rosiglitazone maleate. Res J Pharm Biol Chem Sci 2011;2:833-42.  Back to cited text no. 29
30.Vasava K, Rajesh KS, Jha LL. Formulation and evaluation of floating microspheres of cephalexin. Int J Pharm Sci Rev Res 2011;11:69-75.  Back to cited text no. 30
31.Pandey M, Singh B, Kanoujia J, Saraf S. Formulation and evaluation of floating microspheres of famotidine. Int J PharmTech Res 2010;2:1415-20.  Back to cited text no. 31
32.Pande AV, Vaidya PD, Arora A, Dhoka MV. In vitro and in vivo evaluation of ethyl cellulose based floating microspheres of cefpodoxime proxetil. Int J Pharm Biomed Res 2010;1:122-8.  Back to cited text no. 32
33.Senthilkumar SK, Jaykar B, Kavimani S. Formulation, characterization and in vitro evaluation of floating microsphere containing rabeprazole sodium. JITPS 2010;1:274-82.  Back to cited text no. 33
34.Karthikeyan D, Karthikeyan M, Ramasamy C. Development of floating microspheres to improve oral bioavalibity of cefpodoxime proxetil. Acta Pharm Sci 2010;52:101-4.  Back to cited text no. 34
35.Najmuddin M, Ahmed A, Shelar S, Patel V, Khan T. Floating microspheres of ketoprofen: Formulation and evaluation. Int J Pharm Pharm Sci 2010;2:164-8.  Back to cited text no. 35
36.Tanwar YS, Naruka PS, Jain AK, Jain CP. Formulation, characterization and in vitro evaluation of floating microspheres of famotidine as a gastroretentive dosage form. Asian J Pharm 2009;3:222-6.  Back to cited text no. 36
  Medknow Journal  
37.Chudiwal PD, Pawar PL, Nagaras MA, Mandlik SK, Pandya SV, Wakte P. Statistical evaluation and optimization of influence of viscosity and content of polymer on floating microspheres of clarithromycin. Int J PharmTech Res 2009;1:1366-72.  Back to cited text no. 37
38.Jain AK, Jain CP, Gaur K, Kakde A, Meena M, Nema RK. Effect of natural biodegradable and synthetic polymer for gastric disease by floating microspheres. Cont J Pharm Sci 2009;3:1-6.  Back to cited text no. 38
39.Srivastava AK, Ridhurkar DN, Wadhwa S. Floating microspheres of cimetidine: Formulation, characterization and in vitro evaluation. Acta Pharm 2005;55:277-85.  Back to cited text no. 39
40.Sato Y, Kawashima Y, Takeuchi H, Yamamoto H. In vitro evaluation of floating and drug releasing behaviors of hollow microspheres (microballoons) prepared by the emulsion solvent diffusion method. Eur J Pharm Biopharm 2004;57:235-43.  Back to cited text no. 40
41.Sato Y, Kawashima Y, Takeuchi H, Yamamoto H. In vitro and in vivo evaluation of riboflavin-containing microballoons for a floating controlled drug delivery system in healthy humans. Int J Pharm 2004;275:97-107.  Back to cited text no. 41
42.Shaji J, Shindhe A. Formulation and optimization of pulsatile accelofenac microspheres using response surface methodology. Int Res J Pharm 2012;3:166-9.  Back to cited text no. 42
43.Kumar K, Rai AK. Evaluation of anti-inflammatory and anti-arthritic activities of floating microspheres of herbal drugs. Int Res J Pharm 2012;3:186-93.  Back to cited text no. 43
44.Pandya N, Pandya M, Bhaskar VH. Preparation and in vitro characterization of porous carrier-based glipizide floating microspheres for gastric delivery. J Young Pharm 2011;3:97-104.  Back to cited text no. 44
45.Josephine LJ, Mehul RT, Wilson B, Shanaz B, Bincy R. Formulation and in vitro evaluation of floating microspheres of anti-retroviral drugs as a gastroretentive dosage form. Int J Res Pharm Chem 2011;1:519-27.  Back to cited text no. 45
46.Sanjivani A, Swapnila S, Shalaka D, Uddhav B, Jagdish D. Development and evaluation of hollow microspheres of clarithromycin as gastroretentive drug delivery system using eudragit polymers. Int J Pharma Bio Sci 2011;2:344-58.  Back to cited text no. 46
47.Rao KM, Gnanaprakash K, Chandra SK, Chety CM. Formulation and in vitro characterization of floating microspheres of amoxycillin trihydrate agaist H. pylori. J Pharm Res 2011;4:836-40.  Back to cited text no. 47
48.Samal SB, Dey S, Kumar D, Kumar DS, Sreenivas SA, Rahul V. Formulation, characterization and in vitro evaluation of floating microspheres of nateglinide. Int J Pharma Bio Sci 2011;2:147-56.  Back to cited text no. 48
49.Goyal MK, Mehta SC. Preparation and evaluation of calcium silicate based floating microspheres of amoxicillin. J Appl Pharm Sci 2011;01:137-41.  Back to cited text no. 49
50.Kumar S, Nagpal K, Singh S, Mishra D. Improved bioavailability through floating microspheres of lovastatin. Daru 2011;19:57-64.  Back to cited text no. 50
51.Patel AR, Mahajan AN, Shah DA. Preparation and in vitro characterization of porous carrier-based floating microspheres of model drug for gastric delivery. Sch Res Libr 2011;3:432-42.  Back to cited text no. 51
52.Tamizharasi S, Sivakumar T, Chandra RJ. Formulation and evaluation of floating drug delivery system of aceclofenac. Int J Drug Dev Res 2011;3:242-51.  Back to cited text no. 52
53.Sarode SM, Mittal M, Magar RM, Shelke AD, Shrivastava B, Vidyasagar G. Formulation and evaluation of floating microspheres of Glipizide. J Chem Pharm Res 2011;3:775-83.  Back to cited text no. 53
54.Hu LD, Liu W, Yang JX, Li L. Optimization of gastric floating microspheres of dextromethorphan hydrobromide using a central composite design. Indian J Nov Drug Deliv 2011;3:185-91.  Back to cited text no. 54
55.Bhise SB, More AB, Malayandi R. Formulation and in vitro evaluation of rifampicin loaded porous microspheres. Sci Pharm 2010;78:291-302.  Back to cited text no. 55
56.Phutane P, Shidhaye S, Lotlikar V, Ghule A, Sutar S, Kadam V. In vitro evaluation of novel sustained release microspheres of glipizide prepared by the emulsion solvent diffusion-evaporation method. J Young Pharm 2010;2:35-41.  Back to cited text no. 56
57.Rajkumar M, Bhise S. Carbamazepine-loaded porous microspheres for short-term sustained drug delivery. J Young Pharm 2010;2:7-14.  Back to cited text no. 57
58.Zhao L, Wei YM, Yu Y, Zheng WW. Polymer blends used to prepare nifedipine loaded hollow microspheres for a floating-type oral drug delivery system: In vitro evaluation. Arch Pharm Res 2010;33:443-50.  Back to cited text no. 58
59.Garg R, Gupta GD. Gastroretentive floating microspheres of silymarin: Preparation and in vitro evaluation. Trop J Pharm Res 2010;9:59-66.  Back to cited text no. 59
60.Reddy AB, Karunanidhi M, Karna KS, Rani BS. Effect of SLS on ethyl cellulose containing cyclobenzaprine HCl floating microspheres. Res J Pharm Biol Chem Sci 2010;1:898-909.  Back to cited text no. 60
61.Najmuddin M, Ahmed A, Shelar S, Patel V, Khan T. Formulation and in vitro evaluation of floating microspheres of ketoprofen prepared by emulsion solvent diffusion method. Int J Pharm Pharm Sci 2010;2:13-7.  Back to cited text no. 61
62.Ghodake JD, Vidhate JS, Shinde DA, Kadam AN. Formulation and evaluation of floating microsphere containing anti-diabetic (metformin hydrochloride) drug. Int J PharmTech Res 2010;2:378-84.  Back to cited text no. 62
63.Rahman MH, Chungath TT, Kuppusamy K. Comparative evaluation of HPMC K100 and poloxamer 188-influence on release kinetics of curcumin in floating microspheres. Res J Pharm Biol Chem Sci 2010;1:28-34.  Back to cited text no. 63
64.Barhate SD, Rupnar YS, Sonvane RM, Pawar KR, Rahane RD. formulation and evaluation of floating microspheres of ketorolac trometamol. Int J Pharm Res Dev 2009;1:1-8.  Back to cited text no. 64
65.Wei YM, Zhao L. In vitro and in vivo evaluation of ranitidine hydrochloride loaded hollow microspheres in rabbits. Arch Pharm Res 2008;31:1369-77.  Back to cited text no. 65
66.Jain SK, Agrawal GP, Jain NK. Evaluation of porous carrier-based floating orlistat microspheres for gastric delivery. AAPS PharmSciTech 2006;7:90.  Back to cited text no. 66
67.Jain SK, Awasthi AM, Jain NK, Agrawal GP. Calcium silicate based microspheres of repaglinide for gastroretentive floating drug delivery: Preparation and in vitro characterization. J Control Release 2005;107:300-9.  Back to cited text no. 67
68.Bansal H, Kaur SP, Gupta AK. Microspheres: methods of preparation and applications: A comparative study. Int J Pharm Sci Rev Res 2011;10:69-78.  Back to cited text no. 68
69.Wang A, Lu Y, Sun R. Recent progress on the fabrication of hollow microspheres. Mater Sci Eng A 2007;460-1:1-6.  Back to cited text no. 69
70.Reddy KA, Prathyusha P, Reddy KP, Kumar VN, Prashad NS. Design and evaluation of floating drug delivery systems of cephalexin. J Pharm Biomed Sci 2011;10:1-4.  Back to cited text no. 70
71.Guerrero S, Teijón C, Muñiz E, Teijón JM, Blanco MD. Characterization and in vivo evaluation of ketotifen-loaded chitosan microspheres. Carbohydr Polym 2010;79:1006-13.  Back to cited text no. 71
72.Sun R, Lu Y, Chen K. Preparation and characterization of hollow hydroxyapatite microspheres by spray drying method. Mater Sci Eng C 2009;29:1088-92.  Back to cited text no. 72
73.Naikwade S, Bajaj A. Preparation and in vitro evaluation of budesonide spray dried microparticles for pulmonary delivery. Sci Pharm 2009;77:419-41.  Back to cited text no. 73
74.Motlekar N. Optimization of experimental parameters for the production of LMWH-loaded polymeric microspheres. Drug Des Devel Ther 2009;2:39-47.  Back to cited text no. 74
75.Fu H, Rahaman MN, Day DE, Brown RF. Hollow hydroxyapatite microspheres as a device for controlled delivery of proteins. J Mater Sci Mater Med 2011;22:579-91.  Back to cited text no. 75
76.Fu H, Rahaman MN, Day DE. Effect of process variables on the microstructure of hollow hydroxyapatite microspheres prepared by a glass conversion method. J Am Ceram Soc 2010;93:3116-23.  Back to cited text no. 76
77.Wei W, Ma GH, Wang LY, Wu J, Su ZG. Hollow quaternized chitosan microspheres increase the therapeutic effect of orally administered insulin. Acta Biomater 2010;6:205-9.  Back to cited text no. 77
78.Tzvetkov G, Paradossi G, Tortora M, Fernandes P, Fery A, Graf-Zeiler B, et al. Water-dispersible PVA-based dry microballoons with potential for biomedical applications. Mater Sci Eng C Mater Biol Appl 2010;30:412-6.  Back to cited text no. 78
79.Zhang C, Hou T, Chen J, Wen L. Preparation of mesoporous silica microspheres with multi-hollow cores and their application in sustained drug release. Particuology 2010;8:447-52.  Back to cited text no. 79
80.Li S, Nguyen L, Xiong H, Wang M, Hu TC, She JX, et al. Porous-wall hollow glass microspheres as novel potential nanocarriers for biomedical applications. Nanomedicine 2010;6:127-36.  Back to cited text no. 80
81.Liu G, Wang H, Yang X. Synthesis of pH-sensitive hollow polymer microspheres with movable magnetic core. Polymer 2009;50:2578-86.  Back to cited text no. 81
82.Shen S, Wu W, Guo K, Meng H, Chena J. A novel process to synthesize magnetic hollow silica microspheres. Colloids Surf A Physicochem Eng Asp 2007;311:99-105.  Back to cited text no. 82
83.Yoo HS. Preparation of biodegradable polymeric hollow microspheres using O/O/W emulsion stabilized by labrafil. Colloids Surf B Biointerfaces 2006;52:47-51.  Back to cited text no. 83
84.Wilding IR, Coupe AJ, Davis SS. The role of gamma-scintigraphy in oral drug delivery. Adv Drug Deliv Rev 2001;46:103-24.  Back to cited text no. 84
85.Digenis GA, Sandefer EP, Page RC, Doll WJ. Gamma scintigraphy: An evolving technology in pharmaceutical formulation development-Part 1. Pharm Sci Technol Today 1998;1:100-7.  Back to cited text no. 85
86.Newman SP, Wilding IR. Gamma scintigraphy: An in vivo technique for assessing the equivalence of inhaled products. Int J Pharm 1998;170:1-9.  Back to cited text no. 86
87.Sato Y, Kawashima Y, Takeuchi H, Niva T, Ito Y. Preparation of multiple unit hollow microspheres (microballoons) with acrylic resin containing tranilast and their drug release characteristics (in vitro) and floating behavior (in vivo). J Control Release 1991;16:279-90.  Back to cited text no. 87
88.Harvey CJ, Blomley MJ. Principles and precautions of conventional radiography. Surgery 2005;23:158-161.  Back to cited text no. 88
89.Patil JM, Hirlekar RS, Gide PS, Kadam VJ. Trends in floating drug delivery systems. J Sci Ind Res 2006;65:11-21.  Back to cited text no. 89
90.Miranda JR, Corá LA, Fonseca PR, Stelzer M, Paixão FC, Romeiro FG, et al. Magnetic multiparticulate colonic delivery systems evaluated by AC biosusceptometry. Int Congr Ser 2007;1300:303-6.  Back to cited text no. 90
91.Weitschies W, Wilson CG. In vivo imaging of drug delivery systems in the gastrointestinal tract. Int J Pharm 2011;417:216-26.  Back to cited text no. 91
92.Steingoetter A, Weishaupt D, Kunz P, Mäder K, Lengsfeld H, Thumshirn M, et al. Magnetic resonance imaging for the in vivo evaluation of gastric-retentive tablets. Pharm Res 2003;20:2001-7.  Back to cited text no. 92
93.Pund S, Joshi A, Vasu K, Nivsarkar M, Shishoo C. Gastroretentive delivery of rifampicin: In vitro mucoadhesion and in vivo gamma scintigraphy. Int J Pharm 2011;411:106-12.  Back to cited text no. 93
94.Gangadharappa HV, Biswas S, Getyala A, Gupta V. Development, in vitro and in vivo evaluation of novel floating hollow microspheres of rosiglitazone maleate. Der Pharm Lett 2011;3:299-316.  Back to cited text no. 94
95.Jain SK, Agrawal GP, Jain NK. A novel calcium silicate based microspheres of repaglinide: In vivo investigations. J Control Release 2006;113:111-6.  Back to cited text no. 95
96.Sato Y, Kawashima Y, Takeuchi H, Yamamoto H, Fujibayashi Y. Pharmacoscintigraphic evaluation of riboflavin-containing microballoons for a floating controlled drug delivery system in healthy humans. J Control Release 2004;98:75-85.  Back to cited text no. 96
97.Illum I, Ping H. Gastroretentive controlled release microspheres for improved drug delivery. U.S. Patent 006207197B1. 2001.  Back to cited text no. 97
98.Lohray BB, Lohray BT, Mehta RP, Pai MR, Tiwari SB. Novel floating dosage form. U.S. Patent 0013876. 2006.  Back to cited text no. 98
99.Singh A, Singh S, Puthli S, Tandale R. Programmable buoyant delivery technology. U.S. Patent 0015224A1. 2010.  Back to cited text no. 99
100.Jiang Q. Gastric retention drug delivery system, preparation method and use thereof. European Patent 2329810A1. 2011.  Back to cited text no. 100
101.Li S, Dynan WS, Wicks G, Steven S. Porous wall hollow glass microspheres as carrier for biomolecules. U.S. Patent 0201892A1. 2012.  Back to cited text no. 101
102.Sylvain J, Kirkorian M. Process for making multiparticulate gastroretentive dosage forms. European Patent 2444064A1. 2012.  Back to cited text no. 102


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]


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