MICROSPONGES DRUG DELIVERY SYSTEM

MICROSPONGES DRUG DELIVERY SYSTEM

Tomar and S. Pahwa *

Lloyd Institute of Management and Technology, 11, Knowledge Park-II, Greater Noida, UP, India.

ABSTRACT: Microsponges are novel drug delivery systems made up of cross-linked spongy, polymeric, porous, spherical microspheres particles which vary in size from 5-300 μm. This delivery system as the advantage of producing controlled release formulations of poorly soluble drugs. It increases drug stability, reduces side effects and modifies drug release profiles making it a versatile drug delivery vehicle. These active micro sponges can entrap a wide variety of substances and be incorporated into formulations, such as capsules, gels, liquids, creams and powders and share a broad package of benefits. This article presents a broad review of Micro sponges delivery system (MDS), discussing its characteristics, benefits, different preparation methods (Liquid-Liquid Suspension Polymerization, Quasi-Emulsion Solvent Diffusion) and release mechanisms. It also covers different characterization parameters like particle size, size distribution, morphology, surface topography, loading efficiency, production yield, compatibility studies, true density, in-vitro release studies and MDS systems applications in oral, topical cosmetics bone and tissue.

Keywords: Microsponges, Controlled release, Liquid-Liquid Suspension Polymerization, Quasi-Emulsion Solvent Diffusion

INTRODUCTION: In conventional drug delivery systems, medication has many problems as it requires multi-dose therapy and the absorption of the drug across a biological membrane, whereas the targeted release system releases the drug in a dosage form. In traditional intravascular injection or oral ingestion, the medication is distributed throughout the body through the systemic blood circulation for most therapeutic agents and only a small portion of the medication reaches the organ to be affected. The newer approach, however, delivers the drug into the systemic circulation at a pre-determined rate, known as controlled release drug delivery system ^{1, 3}.

In today’s time, the main focus of pharmaceutical industry is to develop formulations which have controlled or sustained release drug delivery system. In this system the active ingredients resides in a carrier system, which allows changing the time duration of the drug and its therapeutic index ⁴. The micro-sponges technology was first developed by Won in 1987 and the original patent was assigned to advance polymer systems, Inc ^{5, 6}.

Micro-sponge drug delivery systems (MDS) are spherical, porous, polymeric and patented delivery systems that are used for prolonged topical administration. They are spongy tiny like spherical articles of 5 – 300 μm Fig. 1. ⁷ The surface and pore volume can be varied from 20 to 500 m²/g and 0.1 to 0.3 cm^-3/g, respectively. Due to their non-collapsible structure made of interconnecting voids, they are inert and stand in a high degree of shear and hence can be used in the manufacturing of powders, lotions, and creams ^{8, 9}. Micro sponges are designed to deliver a pharmaceutically active ingredient efficiently at a minimum dose and enhance stability, reduce side effects and modify drug release profiles ^{10, 11}. Release of the drug into the skin is facilitated by various factors like pressurizing or rubbing, changes in skin temperature, pH and solubility ⁹. The benefits and limitations of microsponges drug delivery system are mentioned in Table 1.

FIG. 1: IMAGE OF MICROSPONGE

Characteristics of Microsponges:

• MDS system is stable over range of pH 1 to 11 and temperature up to 130 °C.
• They are compatible with most ingredients and vehicles.
• Micro sponge formulations have small pore size of 0.25 µm which inhibit the entry of bacteria so they are self-sterilizing.
• Micro sponge formulations have higher payload (50 to 60%), still free flowing and can be cost effective ¹².

TABLE 1: BENEFITS AND LIMITATIONS OF MICROSPONGE DRUG DELIVERY SYSTEMS ^{13, 16}

Approaches for Formulation of Micro-sponges: Liquid-Liquid Suspension Polymerization (Bottom-up approach) this method of micro-sponges formation is a polymerization method that starts by mixing immiscible polymer (monomer) with the active ingredient in a suitable solvent forming a solution phase. This phase is then dispersed in an aqueous phase containing additives such as surfactants and suspending agents to form suspension. Once the suspension is formed, polymerization is increased by activating the monomers; it can be done by either increasing the temperature or by adding a catalyst ¹⁷. The polymerization process leads to forming a solid spherical structure that has an open-pore surface in reservoir type of system. The solvent is removed, and solid material is then washed and processed to get microsponges. 18Thereaction vessel for micro sponge preparation by liquid-liquid suspension polymerization is shown in Fig. 2.

The Various Steps Involved In the Preparation of Microspongesare ^{17, 21}:

• Picking of monomer and merging of the monomers.
• Chain monomers are formed as polymerization starts.
• Monomer ladder is formed due to cross-linking between chain monomer
• Formation of spherical particles by folding monomer ladder.
• Microsphere bunches are formed by the agglomeration of the microsphere.
• The binding of these bunches leads to the formation of a microsponge.

FIG. 2: REACTION VESSEL FOR MICROSPONGE PREPARATION BY LIQUID-LIQUID SUSPENSION POLYMERIZATION

FIG. 3: METHOD OF QUASI-EMULSION SOLVENT DIFFUSION.

Quasi-Emulsion Solvent Diffusion: ^22-24

• This method is a two-step process known as top-down approach as it starts with preformed polymer, as shown in 3.
• The first step involves the preparation of the inner phase: polymer (Eudragit RS 100) dissolved in solvent (ethyl alcohol). Then the drug is added to the solution and dissolved under ultrasonication at 35 ºC.
• A plasticizer can be added to this solution, such as triethyl citrate (TEC), to enhance plasticity.
• Preparation of external phase: the polyvinyl alcohol solution in distilled water.
• The inner phase is poured into the external phase.
• This mixture is stirred for 60 min and filtered to separate the microsponges.
• The microsponges are then dried in an air-heated oven at 40 °C for 12 h. and weighed to determine production yield.
• Ingredients can be entrapped in micro-sponge polymers at the time of synthesis. They can be post-loaded after the microsphere structure has been pre-formed. The latter process is the preferred mode since many pharmaceuticals, and cosmetic ingredients would decompose at the temperature used for polymerization

Release Mechanism of Microsponge: In micro sponge drug delivery system, the active ingredients are free to move in and out from the particles into the vehicle due to their open structure. This process continues till equilibrium is reached. When the final product is applied to the skin surface, the vehicle starts depleting due to unsaturation disturbing the equilibrium. This causes the flow of the active ingredients from the microspheres into a vehicle and then into the skin surface. In MDS formulations, the sustained release effect can be achieved by altering the release rate of the active ingredients. This can be achieved by modifying the diameter of the pores, the extent of cross-linking of the polymers, the difference in concentration of the active ingredient between the microspheres and the vehicle in which these spheres are entrapped. The release of active ingredients from the microsponges is triggered by external factors, which include pressure, temperature, pH and solubility ^{25, 26}.

Pressure: MDS releases the active ingredient when it is pressurized or rubbed into the skin surface. The released amount of active ingredient depends on the features of microsponges. We can get optimized microsponges for a particular application by varying in different process variables and types of material ^{27, 29}.

Temperature Change: The change in skin temperature affects the release of active ingredients from microsponges onto the skin surface, especially for those MDS formulations which have viscous active ingredients at room temperature and needs high temperature for the sudden flow of active ingredients onto the skin. For example, viscous sunscreens were found to show a higher release from micro-sponges when exposed to higher temperatures; thus, sunscreen would be released from a micro-sponge only upon exposure to heat from the sun ^{30, 31}.

Solubility: The solubility of an active ingredient in MDS depends on dissolving medium, concentration gradient diffusion in consideration with the partition coefficient of the ingredient between the microsponges and the outside system. The antiseptics and antiperspirants are water-miscible active ingredients, and release of these active ingredients will occur only in water medium. The release can also be activated by diffusion, taking into consideration the partition coefficient of the ingredients between the microsponges and the outside system ^{30, 32}.

pH: By applying a pH-specific coating on the microsponges, we can trigger the release of active ingredients at a particular pH ²⁷.

Characterization of Micro-sponges:

Particle Size and Size Distribution: Particle size and size distribution of microsponges affect the texture and stability of the formulation and affect drug release. So, it is a very crucial step for microsponge formulation. Particle size and size distribution of loaded and unloaded microsponges are evaluated by using laser light diffract geometry. To study the effect of particle size on drug release, a graph of cumulative percentage drug release vs. particle size will be plotted against time ^{26, 33}.

Morphology and Surface Topography: To study morphology and surface topography, micro sponges are coated with gold-palladium under an argon atmosphere at room temperature, then examined using Scanning electron microscopy (SEM) or Transmission electron microscopy (TEM) ³⁴.

Determination of Loading Efficiency and Production Yield: The loading efficiency percentage of microsponges can be calculated by using the following equation ³⁵:

Loading Efficiency (%) = (Actual Drug Content in Microsponges) / (Theoretical Drug Content) × 100

The production yield of microsponges can be determined by accurately calculating the initial weight of the raw materials and the final weight of the microsponge obtained.

Production yield = (Practical mass of microsponges) / (Theoretical mass (polymer + drug) × 100

Compatibility Studies: Compatibility study of drugs with excipients can be studied by Fourier Transform Infra-red spectroscopy (FT-IR). Differential scanning colorimetry (DSC) and powder X-ray diffraction (XRD) are used to study the effect of polymerization on the crystallinity of the drug. For DSC, approximately weigh and seal 5 mg of sample in an aluminum pan and then run it at a heating rate of 15 °C/min over a temperature range 25-430 °C in nitrogen atmosphere ³⁶.

Characterization of Pore Structure: Pore volume and diameter of microsponges are crucial in controlling the intensity and duration of action of active ingredients. Pore diameter of microsponges also shows the effect in the movement of active ingredients into the vehicle in which the material is dispersed.

The effect of pore diameter and volume on release rate of drug can be studied by Mercury intrusion porosime try. It also helps in determining total pore surface area, average pore diameters, pore size distribution, shape, morphology, bulk and apparent density of the pores ³⁴.

Determination of True Density: The true density of micro-spherical particles can be determined using an ultra-pycnometer under helium gas and is calculated from a mean of repeated determinations ³⁷.

Resiliency Viscoelastic Properties: Micro sponges can be made softer or rigid according to the needs of formulation by modifying its Resiliency viscoelastic properties. Increased cross-linking leads to a slow drug release rate.

Hence resiliency of Micro sponges is studied and optimized as per the need by considering release as a function of cross-linking with time ³⁸.

In-vitro Release Studies: USP XXIII dissolution apparatus equipped with a modified basket consisted of 5 µm stainless steel mesh is used to perform the In-vitro release studies of mico sponges. The apparatus is run at 150 rpm at37 °C to measure dissolution rate. The selection of dissolution medium depends upon the solubility of active ingredients to maintain sink conditions. The samples are withdrawn at regular time intervals and analyzed by suitable analytical methods (UV spectrophotometer ³⁹.

Polymer / Monomer Composition: The selection of monomer is done depending on the characteristics of the drug which reside inside it and the vehicle in which the drug gets dispersed. The partition coefficient between the vehicle and the microsponge system and the release rate of the drug depends on polymer composition. The drug release also depends on several factors such as particle size, drug loading, and polymer composition. The release of drugs from micro-sponge systems of different polymer compositions can be studied by plotting cumulative percentage drug release against time. To check the compatibility of drug with the polymer, different drug-polymer combinations are made, and their drug release profile is studied ^{40, 41}.

Stability Studies: Stability studies are performed to ensure that there is no change in the physical, chemical, microbiological, therapeutic, and toxicological properties of formulation during its storage in a particular container or closure system. The prepared formulation os tested for stability on storing them at 4 ± 1 ºC, 25 ± 2 ºC and 37 ± 5 ºC & RH (Relative Humidity) 75%. After one month and three months, they are evaluated for the following parameters-appearance, pH, drug content analysis, drug release profiles, rheological properties, etc. ^{42, 43}

Applications of Microsponges Drug Delivery System: MDS are used to modify drug release; they deliver the drug efficiently in low dose with enhanced stability and low side effects. This system is used to prepare oral, topical and bio-pharmaceutical formulations. It also offers the formulator a range of alternatives to develop drug and cosmetic products.  This is due to the high loading capacity and sustained release ability of micro sponges ^{44, 45}. The applications of different active ingredients in a microsponge formulation is given in Table 2. Its marketed formulations are mentioned in Table 3; examples of microsponge drug delivery with their formulations are given in Table 4 and Patents filed in Table 5.

TABLE 2: APPLICATIONS OF DIFFERENT ACTIVE INGREDIENTS IN MICROSPONGES FORMULATION ^{44, 45}.

For Topical Administration: Release of the drug into the skin is facilitated by a various factor like pressuring or rubbing, change in skin temperature, pH and solubility⁹. Genetically engineered melanin is incorporated in microsponges (sunscreens), melanosponge-α to spread it evenly hence providing protection against UV-A and UV-B radiation 46 Fluocinolone Acetonide (FA) is a corticosteroid primarily used in dermatology to reduce skin inflammation and relieve itching ¹⁶.

For Oral Administration: In the oral drug delivery system, MDS is used to increase the solubility of poorly water-soluble drugs by entrapping such drugs in its pores. Due to tiny pores of microsponges the drug is reduced to microscopic particles, hence increased surface area, thus greatly increasing the solubility. The drug in the microsponges resides in a protected environment, which provides controlled delivery of the drug to the lower gastrointestinal (GI) tract, where it is released upon exposure to specific enzymes in the colon. Additionally, the MDS system increases the GI retention time of the drug, thus increasing absorption ^{47, 48, 49, 50}.

Microsponge for Bone and Tissue Engineering: The microsponges for the bone substituted compound are prepared in pre-polymerized powders of polymethyl-methacrylate and liquid methylmethacrylate monomer with two aqueous dispersions of a-tri calcium phosphate (a-TCP) grains and calcium-deficient hydroxylapatite (CDHA) powders. The fibroblast growth factor (bFGF) incorporated in a collagen sponge sheet was sustained release in the mouse subcutis according to the biodegradation of the sponge matrix and exhibited local angiogenic activity in a dose-dependent manner 51 A biodegradable graft material containing the collagen micro sponge was developed for cardiovascular tissue grafting, as it would permit the regeneration of the autologous vessel tissue ⁵².

Long-Lasting Coloured Cosmetics: Coloured cosmetics formulated with micro-sponges entrapment are highly graceful due to uniform spreading and improved covering; it includes coloured cosmetic products such as rouge or lipsticks ^{53, 54}. Some marketed formulations of microsponges are given in Table 3.

Recent Advances in Microsponge Drug Delivery System: With the development of nanotechnology, the Pharmaceutical Industry has become very advanced; they shifted the formulation process from micro to nanosized particles. Nanosponges are hyper cross-linked polymer based colloidal structures, consisting of countless interconnecting voids within a collapsible structure with porous surface ⁷². These sponges are incorporated in cosmetics and sunscreens as antioxidants and antireflectants ⁷⁶. 77β - CD nanosponges were developed that can be used for hydrophilic as well as hydrophobic drugs like Flurbiprofen, dexamethasone, itraconazole, doxorubicin hydrochloride and serum albumins model drug. These nanosponges were developed by cross- linking the β CD molecule by reacting it with Biphenylcarbonate. Some researchers also observed nanosponges as a good carrier for the delivery of gases. Researchers also observed that incorporating a cytotoxic in a nanosponge carrier system can increase the potency of the drug, suggesting that these carriers can be potentially used for targeting the cancerous cells ⁷⁸. Swaminanthan et al., 2007 formulated cyclodextrin nanosponges for solubility enhancement of itraconazole, a poorly water-soluble drug ⁷⁹. Sharma and Pathak, 2011 fabricated ethyl cellulose nanosponges as an alternative system for targeting econazole nitrate to the skin through hydrogel formulation ⁸⁰. Improved stability of RNA and a relatively effective encapsulation process of siRNA was prepared. The approach could lead to novel therapeutic routes for siRNA delivery ⁸¹. The babchi oil-loaded cyclodextrin nanosponges were also fabricated by a research group for solubility and photostability enhancement of entrapped essential oils ⁸².

TABLE 3: MARKETED FORMULATIONS OF MICROSPONGES ^{55, 62}

TABLE 4: EXAMPLES OF MICROSPONGE DRUG DELIVERY WITH THEIR FORMULATIONS ^{63, 65}

TABLE 5: PATENTS FILED RELATED TO MICROSPONGES ^{66, 74}

CONCLUSION: MDS is a spherical, porous, polymeric, and patented delivery system used for prolonged topical administration. It is used to increase the solubility of poorly water-soluble drugs by entrapping such drugs in the micro sponges pores. Due to the tiny pores of microsponges, the drug is reduced to microscopic particles, hence increased surface area thus, this greatly increases the solubility. Micro sponges are designed to deliver a pharmaceutically active ingredient efficiently at a minimum dose with enhanced stability, reduced side effects and modified drug release profiles. In this system, the active ingredient resides in a carrier system, which allows us to change the time duration of the drug and its therapeutic index. With the help of MDS system, we can prepare the formulation of immiscible products and also improves material processing, e.g., liquid can be converted to powders. This system is used to prepare oral, topical and biopharmaceutical formulations. It also offers the formulator a range of alternatives to develop drug and cosmetic products.  This is due to the high loading capacity and sustained release ability of microsponges. Hence, microsponge-based formulations are control released and have better therapeutic effects than conventional formulation.

ACKNOWLEDGEMENT: Nil

CONFLICTS OF INTEREST: Nil

REFERENCES:

1. Saltzman WM and Torchilin VP: Drug delivery system. McGraw-Hill. Companies 2008.
2. Trafton A: Tumors targeted using tiny gold particles. MIT Tech Talk 2009.
3. Panchagnula R: Transdermal delivery of drugs. Indian Journal of Pharmacology 1997; 29: 140-56
4. Saxena S and Nacht S: Delivery system handbook for personal care and cosmetic products: technology, applications and formulations. William Andrew Publishing 2005.
5. Won R: Method for delivering an active ingredient by controlled time release utilizing a novel delivery vehicle which can be prepared by a process utilizing the active ingredients as a Porogen. US Patent No 4690825, 1987.
6. Kydonieus AF and Berner B: Transdermal delivery of drugs. CRC Press 1987.
7. Vyas SP and Khar RK: Targeted and controlled drug delivery-Novel carrier system. CBS Publication 2002.
8. Kumar JR, Muralidhara S and Ramasamy S: Microsponges enriched gel (megs): a novel strategy for ophthalmic drug delivery system containing ketotifen. Journal of Pharmaceutical Sciences & Research 2013; 5(4): 97-102.
9. Kumar SP: Micro spongesas the versatile tool for drug delivery system. International Journal of Research in Pharmacy and Chemistry 2011; 1(2): 243-58.
10. Charde MS, Ghanawat PB, Welankiwar AS, Kumar J and Chakole RD: Microsponge a novel new drug delivery system a review. International Journal of Advances in Pharmaceutics 2013; 2(6): 63-70.
11. Newton DW: Biotechnology frontier: targeted drug delivery. US Pharmacist 1991; 16: 38-39.
12. D’Souza JI, Masvekar RR, Pattekari PP, Pudi SR and More HN: Microspongic delivery of fluconazole for topical application. Indo-Japanese International Conference on Advance Pharmaceutical Research and Technology 2004; 7.
13. Sarika AN, Mayura SC, Sankaye A, Gaikwad VB and Mahaparale PR: Micro sponges for topical drug delivery system an overview. International Research Journal for Inventions in Pharmaceutical Sciences 2014; 2(5): 202-07.
14. Patidar K, Soni M, Saxena C, Soni P and Sharma DK: Microsponges versatile vesicular approach for transdermal drug delivery system. Journal of Global Pharma Technology 2010; 2(3): 154164.
15. Aloorkar NH, Kulkarni AS, Ingale DJ and Patil RA: Micro sponges as innovative drug delivery systems. International Journal of pharmaceutical Sciences and Nanotechnology 2012; 5(1): 1597-06.
16. D’Souza JI and More HN: Topical Anti-Inflammatory Gels of fluocinolone acetonide entrapped in eudragit based microsponge delivery system. Research Journal of Pharmacy and Technology 2008; 1(4): 502-06.
17. Tansel C¸ Omoglu G and Baykara T: The effects of pressure and direct compression on tableting of micro-sponges. Int Journal of Pharmaceutics 2002; 242: 191-95.
18. Anderson DL, Cheng CH and Nacht S: Flow characteristics of loosely compacted macroporous Micro sponge polymeric systems. Powder Tech 1994; 78: 15-18.
19. Panwar AS, Yadav CS, Yadav P, Darwhekar GN, Jain DK, Panwar MS and Agrawal A: Micro sponge a novel carrier for cosmetics. Journal of Global Pharma Technology 2011; 3(7): 15-24.
20. Vikrant K, Nikam RT, Somwanshi SB, Gaware VM, Kotade KB, Dhamak KB, Khadse AN and Kashid VA: Microparticles: a novel approach to enhance the drug delivery - a review. Intenational Journal of Pharmaceutical Research and Development 2011; 3(8): 170-83.
21. Brunton LL, Lazo JS and Parker KL: Goodman and gilman’s pharmacological basis of therapeutics. McGraw Hill Education, Eleventh Edition 2006
22. Orlu, Cevher M and Araman EA: Design and evaluation of colon specific drug delivery system containing flurbiprofen micro sponges. Int J Ph 2006; 318: 103-17.
23. Kawashima Y, Niwa T, Takeuchi H, Hino T and Ito Y: Control of prolonged drug release and compression properties of ibuprofen microsponges with acrylic polymer, eudragitby changing their intraparticleporosity. Chemical &Pharmaceutical bulletin 1992; 40: 196-01.
24. Embil K and Nacht S: The microsponge delivery system a topical delivery system with reduced irritancy incorporating multiple triggering mechanisms for the release of actives. Journal of Microencapsulation 1996; 13: 575-88.
25. Khopade AJ, Jain S and Jain NK: The microsponge. Eastern Pharmacist 1996; 49-53.
26. Patil SS, Dandekar V, Kale A and Barhate SD: Micro sponges drug delivery system An overview. European Journal of Pharmaceutical and Medical Research 2016; 3(8): 212-21.
27. Christensen MS, Hargens CW, Nacht S and Gans EH: Viscoelastic properties of intact human skin instrumentations, hydration effects and contribution of the stratum corneum. Journal of Investigative Dermatology 1977; 69: 282-86
28. Christensen MS and Natch SJ: Safety of Microsponges. Investigational Dermatology 1983; 69: 282.
29. Chadawar V and Shaji J: Microsponge delivery. Current Drug Delivery 2007; (4); 123-29.
30. Sato T, Kanke M, Schroeder G and Deluca P: Porous biodegradable microspheres for controlled drug delivery, assessment of processing conditions and solvent removal techniques. Pharmaceutical Research 1988; (5): 21-30.
31. Mandava SS and Thavva V: Novel approach micro sponges drug delivery system. International Journal of pharmaceutical Science and Research 2012; 3(4): 967-80.
32. Mishra MK, Shikhri M, Sharma R and Goojar MP: Optimization, formulation development and characterization of eudragit rs 100 loaded microsponges and subsequent colonic delivery. International Journal of Drug Discovery and Herbal Research 2011; 1(1): 8-13.
33. Martin A, Swarbrick J and Cammarrata A: Physical pharmacy: physical chemical principles in the pharmaceutical sciences. Lea & Febiger Third Edition 1991.
34. Emanuele AD and Dinarvand R: Preparation, characterization and drug release from thermo responsive microspheres. International Journal of Pharmaceutics 1995; 237-42
35. Kumar S, Tyagi LK and Singh D: Microsponge delivery system (MDS): A unique technology for delivery of active ingredients. International Journal of Pharmaceutical Science and Research 2011; 2(12): 3069-80.
36. D’Souza JI: Themicrosponge drug delivery system for delivering an active ingredient by controlled time release Pharmainfo. Net 2008; 6: 62.
37. Kapoor D, Vyas RB, Lad C, Patel M and Tyagi BL: A review on microsponge drug delivery system. Journal of Drug Delivery & Therapeutics 2014; 4(5): 29-35.
38. Barkai A, Pathak V and Benita S: Polyacrylate (Eudragit retard) microspheres for oral controlled release of nifedipine, formulation design and process optimization. Drug Develop and Industrial Pharmacy 1990; 16: 2057-75.
39. D’SouzaJ I: In-vitro antibacterial and skin irritation studies of microsponges of benzoyl peroxide. Indian Drugs 2001; 38: 361-62
40. Chowdary KPR and Rao YS: Mucoadhesive microspheres for controlled drug delivery. Biological and Pharmaceutical Bulletin 2004; 27(11): 1717-24.
41. Wakiyama N, Juni K and Nakano M: Preparation and evaluation in-vitro of polylactic acid microspheres containing local anesthetic. Chemical and Pharmaceutical Bulletin Tokyo 1981; 29: 3363-68.
42. Amrutiya N, Bajaj A and Madhu: Development of microsponges for topical delivery of mupirocin. AAPS Pharm Sci Tech 2009; 10(2): 402-09.
43. Jain V and Singh R: Dicyclomine loaded eudragit based microsponge with potential for colonic delivery: Preparation and characterization. Tropical Journal of Pharmaceutical Research 2010; 9: 67-72.
44. Mandava SS and Thavva V: Novel approach: microsponge drug delivery system. International Journal of Pharmaceutical Science and Research 2012; 3(4): 967-80
45. Jadhav N, Patel V, Mungekar S, Bhamare G, Karpe M and Vilasrao K: Microsponge Delivery System: An updated review, current status and future prospects. Journal of Scientific and Innovative Research 2013; 2(6): 1097-10.
46. Patravale VB and Mandawgade SD: Novel cosmetic delivery systems: an application update. International Journal of Cosmetic Science 2008; 30: 19-33.
47. Kawashima Y, Niawa T, Takeuchi H, Hino T and Itoh Y: Hollow macrospheres for use as a Floating controlled drug effect system in the stomach. Journal of Pharmaceutical Science 1992; 82(2): 135-40.
48. Yang M, Cui F and You B: Preparation of sustained release nitrendipine microspheres with Eudragit RS and Aerosil using quasi-emulsion solvent diffusion method. Internationl Journal of Pharmaceutics 2003; 259: 103-13.
49. Jain V and Singh R: Development and characterization of eudragit RS 100 loaded micro sponges and its colonic delivery using natural polysaccharides. Acta Poloniae Pharmaceutical-Drug Research 2010; 67: 407-15.
50. Mishra MK, Shikhri M, Sharma R and Goojar MP: Optimization formulation development and characterization of Eudragit RS 100 loaded micro sponges and subsequent colonic delivery. International Journal of Drug Discovery and Herbal Research 2011; 1(1): 8-13.
51. Berutoa DT, Bottera R and Fini M: The effect of water in inorganic micro sponges of calcium phosphates on the porosity and permeability of composites made with poly methyl methacrylate. Biomaterials 2002; 23: 2509-17.
52. Chen G, Ushida T and Tateishi T: A biodegradable hybrid sponge nested with collagen microsponges. J Biomed Mater Res 2000; 51: 273-79.
53. Kanematsu A, Marui A, Yamamoto S, Ozeki K, Hirano Y, Yamamoto M, Ogawa O, Komeda M and Tabata Y: Type 1 collagen can function as a reservoir of basic fibroblast growth factor. Journal of Control Rele 2004; 99: 281-92.
54. Iwai S, Sawa Y, Ichikawa H, Taketani S, Uchimura E, Chen G, Hara M, Miyake J and Matsuda H: Biodegradable polymer with collagen micro sponge serves as a new bioengineered cardiovascular prosthesis. Journal of Thoracic and Cardio Vascular surgery 2004; 128; 472-79
55. Shyam SM and Vedavathi T: Novel approach micro sponge drug delivery system. International Journal of Pharmaceutical Science and Research 2012; 1(3): 967-80
56. Srivastava R and Pathak K: Microsponges a futuristic approach for oral drug delivery. Expert Open Drug Delivery 2012; 9(7): 863-78.
57. Rossi S and Buckley N: Australian Medicines Handbook. Adelaide 2006.
58. Baselt R: Disposition of toxic drugs and chemicals in man. Biomedical Publications, Eight Edition 2008.
59. Jones DS and Pearce KJ: Investigation of the effects of some process variables on, microencapsulation of propranolol HCl by solvent evaporation method. International Journal of Pharmaceutics 1995; 118: 99-205.
60. Talisuna AO, Bloland PD and Alessandro U: History, dynamics & public health importance of malaria parasite resistance. Clinical Micro Review 2004; 17: 235-54.
61. Patel SB, Patel HJ and Seth AK: Microsponge drug delivery system: an overview. Journal of Global Pharma Technology 2010; 2: 1-9
62. Delattre L and Delneuville I: Biopharmaceutical aspects of the formulation of dermatological vehicles. Journal of the European Academy of Dermatology Venereology 1995; 5: 70-71.
63. Peppas NA: Analysis of Fickian and Non-Fickian drug release from polymers. Pharmaceutica Acta Helvetiae 1985; 60: 110-11.
64. Guyot M andFawaz, F: “Microspheres- Preparation and physical characteristics”. International Journal of Pharmaceutics1998; 175: 61-74.
65. Gangadharappa HV, Gupta V, Sarat CPM and Kumar SHG: Current trends in microsponge drug delivery system. Current Drug Delivery 2013; 10: 453-65.
66. Won AJ and Min CS: Micro sponges having controlled solubility and improved redissolution property. J 2016.
67. Tamarkin D: Non surface-active agent non polymeric agent hydro-alcoholic foamable compositions, breakable foams and their uses. 2015; 2.
68. Paula T: Nucleic acid particles, methods and use thereof. 2015; US9737557B2.
69. Eugenia P and Kharlampieva: Biodegradable Photo-catalytic Nanocomposite Microsponges of Polylactic acid. 2014; US20140102991 A1.
70. Chari K: Surfactant responsive micro-gels. 2012; US9096755B2.
71. Love FS: Nonwoven towel with micro sponges. 2008; US7426776B2.
72. Mcdaniel DH: Method and apparatus for acne treatment using low intensity light. Therapy 2007; CA2644219C.
73. Tamarkin D: Foamable vehicle and vitamin and flavonoid pharmaceutical compositions thereof. 1997; US20080069779A1.
74. Gangadharappa HV, Gupta NV, Prasad MS and Shivakumar HG: Current trends in micro sponge drug delivery system. Curr Drug Delivery 2013; 10(4): 453-65.
75. Tejashri G, Amrita B and Darshana J. Cyclodextrin based nanosponges for pharmaceutical use: a review. Acta Pharm 2013; 63(3): 335-58.
76. Xiao L, Takada H, Maeda K, Haramoto M and Miwa N: Antioxidant effects of water-soluble fullerene derivatives against ultraviolet ray or peroxylipidthrough their action of scavenging the reactive oxygen species in human skin keratinocytes. Biomedicine and Pharma 2005; 59: 351-58.
77. Monteiro-Riviere NA, Wiench K, Landsiedel R, Schulte S, Inman AO and Riviere JE: Safety evaluation of sunscreen formulations containing titanium dioxide and zinc oxide nanoparticles in uvb sunburned skin. An In-vitro and in-vivo Toxicological Sciences 2011; 123: 264-80.
78. Trotta F, Cavalli R and Tumiatti W: Cyclodextrin-based nanosponges for drugdelivery. Journal of Inclusion Phenomena Macrocyclic Chemistry 2006; 56: 209-13.
79. Swaminathan S, Vavia PR, Trotta F and Torne S: Formulation of beta cyclodextrin based nano sponges of itraconazole. J of Inclu Phenomena Macrocyclic Chemistry 2007; 57(14): 89-94.
80. Sharma R and Pathak K: Polymeric nanosponges as an alternative carrier for improved retention of econazole nitrate onto the skin through topical hydrogel formulation. Pharma Development and Technolo 2011; 16(4): 367-76.
81. Lee JB, Hong J and Bonner DK: Self-assembled RNA interference micro sponges for efficient siRNA delivery. Nat Materials 2012; 11: 316-22.
82. Kumar S, Pooja, Trotta F and Rao R: Encapsulation of babchi oil in cyclodextrin-based nanosponges: physicochemical characterization, photodegradation and in-vitro cytotoxicity studies. Pharmaceutics 2018; 10(4): 169.
    

    ---

    How to cite this article:

    Tomar M and Pahwa S: Microsponges drug delivery system. Int J Pharm Sci & Res 2021; 12(9): 4697-07. doi: 10.13040/IJPSR.0975-8232.12(9).4697-07.

    ---

    All © 2021 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.