ROLE OF MICROSPHERES IN NOVEL DRUG DELIVERY SYSTEMS: PREPARATION METHODS AND APPLICATIONS
DOI:
https://doi.org/10.22159/ijcpr.2020v12i3.38326Keywords:
Microspheres, Drug delivery, Polymeric, Improved stabilityAbstract
Microsphere based drug delivery system has gained substantial attention in the modern era. Microspheres are normally free-flowing powders that can be made with both natural and synthetic polymers. The sizes of the microspheres ranges from 1 to 1000 µm. Microspheres are matrix systems in which the drug is uniformly dispersed, dissolved or suspended. Microspheres contain solid or liquid drug dissolved or dispersed in a matrix system. The current review provides an inclusive outline of up to date and novel developments on formations of microspheres which have been reported to increase bioavailability, improves stability, enhances biological half-life and reduces the toxicity of the drug. Microsphere provides efficient delivery of various proteins and peptide molecules. There are different types of microspheres such as bio adhesive microsphere, magnetic microsphere, floating microsphere, and polymeric microspheres. Diverse kinds of methods are used in the formulation of microsphere e. g. Simple emulsion-based method, Double emulsion-based method, Interfacial deposition technique, Interfacial polymerization technique, Phase separation method, and Spray drying. Microspheres deliver the drug in a controlled manner through different routes like oral, topical, naso-pulmonary and gene therapy. The Polymeric based microspheres are model carriers for numerous controlled delivery applications owing to their capacity to encapsulate a diversity of drugs, bio-compatibility, high bio-availability and continuous drug release character. Therefore, by developing newer techniques, it can give more therapeutic effects and improves the safety of drugs. The formation of microspheres has been reported to increase bioavailability, improves stability, enhances biological half-life and reduces the toxicity of the drug.
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References
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13. Singh I, Kamboj S, Rana V. Quality by design based fabrication of iron oxide induced mucoadhesive microspheres for enhanced bioavalibility of cinnarizine. Curr Drug Delivery 2017;14:1154–69.
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22. Wang SJ, Lin WY, Chen MN, Hsieh BT, Shen LH, Tsai ZT, et al. Rhenium-188 microspheres: a new radiation synovectomy agent. Nucl Med Commun 1998;19:427–33.
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24. Davis SS, Illum L. Polymeric microspheres as drug carriers. Biomaterials 1988;9:111-2, IN5, 113-5.
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26. Saralidze K, Koole LH, Knetsch MLW. Polymeric microspheres for medical applications. Materials (Basel) 2010;3:3537–64.
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28. Pavan KB, Chandiran IS, Bhavya B, Sindhuri M. Microparticulate drug delivery system: a review. Indian J Pharm Sci Res 2011;1:19-37.
29. Sinha VR, Singla AK, Wadhawan S. Chitosan microspheres as a potential carrier for drugs. Int J Pharm 2004;274:1–33.
30. Mokhtare B, Cetin M, Ozakar RS, Bayrakceken H. Preparation of metformin HCl-loaded chitosan microspheres and in vitro characterization studies. Hacettepe University J Faculty Pharm 2015;35:74-86.
31. Sinha VR, Bansal K, Kaushik R. Polycaprolactone microspheres and nanosphere’s. Int J Pharm 2004;278:1–23.
32. Jain NK. Controlled and novel drug delivery. 4th Ed. New Delhi: CBS Publishers; 2006. p. 236-7.
33. Gohel MC, Parikh RK, Nagori SA, Gandhi AV, Shroff MS, Patel PK, et al. A spray drying a review. Pharm Rev 2009;7;2-23.
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36. Sinha VR, Bansal K, Kaushik R. Polycaprolactone microspheres and nanosphere’s. Int J Pharm 2004;278:1–23.
37. He P, Davis SS, Illum L. Chitosan microspheres prepared by spray drying. Int J Pharm 1999;187:53–65.
38. Christina E. Prepration of microspheres of diclofenac sodium by ionotropic gelation technique. Int J Pharm Pharm Sci 2012;5:228-31.
39. McGinity JW, O'Donnell PB. Preparation of microspheres by the solvent evaporation technique. Adv Drug Delivery Rev 1997;28:25-42.
40. Sudhamani T, Reddy N, Ravi Kumar V, Revathi R, Ganesan V. Preparation and evaluation of ethyl cellulose microspheres of ibuprofen for sustained drug delivery. Int J Pharm Res Dev 2010;2:119-25.
41. Merkel HP, Speister P. Preparation and in vitro evaluation of microspheres using cellulose acetate phthalate. J Pharm Sci 1973;62:1444-8.
42. Rahman M, Islam M, Sharmin N, Chowdhury J, Jalil R. Preparation and evaluation of cellulose acetate phthalate and ethyl cellulose-based microcapsules of diclofenac sodium using emulsification and solvent evaporation method. Dhaka University J Pharm Sci 2010;9:39-46.
43. Chaturvedi K, Kulkarni AR, Aminabhavi TM. Blend microspheres of poly(3-hydroxybutyrate) and cellulose acetate phthalate for colon delivery of 5-fluorouracil. Ind Eng Chem Res 2011;50:10414-23.
44. Beyger JW, Nair JG. Some factors affecting the microencapsulation of pharmaceuticals with cellulose acetate phthalate. J Pharm Sci 1986;75:573-8.
45. Farid DJ, Nokhodchi A. Dissolution of compacted aspirin microcapsules. Ind J Pharm Sci 1991;53:222-3.
46. Maharaji I, Nairn JG, Cambell JB. Simple rapid method for the preparation of enteric-coated microcapsules. J Pharm Sci 1984;73:39-42.
47. Lin CY, Lin SJ, Yang YC, Wang DY, Cheng HF, Yeh MK. Biodegradable polymeric microsphere-based vaccines and their applications in infectious diseases. Hum Vaccin Immunother 2015;11:650-6.
48. Kohn J, Niemi SM, Albert EC, Murphy JC, Langer RS, Fox JG. Single-step immunization using a controlled release, biodegradable polymer with sustained adjuvant activity. J Immunol Methods 1986;95:31-7.
49. Gupta RK, Singh M, O'Hagan DT. Poly(lactide-co-glycolide) microparticles for the development of single-dose controlled-release vaccines. Adv Drug Delivery Rev 1998;32:225-46.
50. Nellore RV, Pande PG, Young D, Bhagat HR. Evaluation of biodegradable microspheres as vaccine adjuvant for Hepatitis B surface antigen. J Parenteral Sci Tech 1992;46:176-80.
51. Desai KG, Schwendeman SP. Active self-healing encapsulation of vaccine antigens in PLGA microspheres. J Controlled Release 2013;165:62-74.
52. Cui Y, Cui P, Chen B, Li S, Guan H. Monoclonal antibodies: formulations of marketed products and recent advances in novel delivery system. Drug Dev Ind Pharm 2017;43:519-30
53. Sailaja AK, Anusha K, Jyothika M. Biomedical applications of microspheres. J Modern Drug Discovery Drug Delivery Res 2015;4:1-5.
54. Adamson P, Wilde T, Dobrzynski E, Sychterz C, Polsky R, Kurali E, et al. Single ocular injection of a sustained-release anti-VEGF delivers 6 mo pharmacokinetics and efficacy in a primate laser CNV model. J Controlled Release 2016;244:1–13.
55. Stern M, Ulrich K, Geddes DM, Alton EWFW. Poly (D, L-lactide-co-glycolide)/DNA microspheres to facilitate prolonged transgene expression in airway epithelium in vitro, ex vivo and in vivo. Gene Ther 2003;10:1282-8.
56. Liu W, Borrell MA, Venerus DC, Mieler WF, Kang Mieler JJ. Characterization of biodegradable microsphere-hydrogel ocular drug delivery system for controlled and extended-release of ranibizumab. Curr Eye Res 2018;44:264-74.
57. Lubben IMVD, Kersten G, Fretz MM, Beuvery C, Verhoef JC, Junginger HE. Chitosan microparticles for mucosal vaccination against diphtheria: oral and nasal efficacy studies in mice. Vaccine 2003;21:1400-8.
58. Rathananand M, Kumar DS, Shirwaikar A, Kumar R, Kumar S, Prasad RS. Preparation of mucoadhesive microspheres for nasal delivery by spray drying. Indian J Pharm Sci 2007;69:651-7.
59. Pereswetoff Morath L. Microspheres as nasal drug delivery systems. Adv Drug Delivery Rev Adv Drug Delivery Rev 1998;29:185-94.
60. Nigam J, Pandey P, Mishra MK. Formulation and evaluation of anti-emetic microspheres for nasal drug delivery system. Indian J Novel Drug Delivery 2017;9:44-53.
61. Saez VC, Hernandez JR, Peniche C. Microspheres as delivery systems for the controlled release of peptides and proteins. Biotecnol Aplicada 2007;24:108-16.
62. Ma G. Microencapsulation of protein drugs for drug delivery: strategy, preparation, and applications. J Controlled Release 2014;193:324-40.
63. Thundimadathil J. Peptide therapeutics: strategy and tactics for chemistry manufacturing and controls. In: Srivastava V. editor. Formulations of microspheres and nanoparticles for peptide delivery. 1st edition. Cryodon: Royal Society of Chemistry; 2019. p. 503-30.
64. Rajput MS, Agrawal P. Microspheres in cancer therapy. Indian J Cancer 2010;47:458-68.
65. Midha K, Nagpal M, Arora S. Microspheres: a recent update. Int J Recent Sci Res 2015;6:5859-67.
66. Singh A, Sharma PK, Malviya R. Sustained drug delivery using mucoadhesive microspheres: the basic concept, preparation methods and recent patents. Recent Patents Nanomed 2012;2:62-77.
67. Mishra N, Goyal AK, Khatri K, Vaidya B. Biodegradable polymer based particulate carrier(s) for the delivery of proteins and peptides. Anti-Inflammatory Anti-Allergy Agents Med Chem 2008;7:240-51.
68. Jin T, Hu Z, Yuan W. Microspheres for controlled-or sustained-release delivery of therapeutics. U. S. Patent number-US9381159B2; 2016.
69. Lewis AL, Tang Y, Stratford PW. Microspheres for treatment of brain tumors, US 8,691,791 B2; 2014.
70. Singh A, Singh S, Puthli S, Tandale R. Programmable buoyant delivery technology. U. S. Patent number US 8,277,843 B2; 2012.
71. Chandler DJ, Austin Bedre J. Magnetic microspheres for use in fluorescence-based applications. U. S. Patent Number US 7,718,262 B2; 2010.
72. Ilum L, Ping H. Gastroretentive controlled-release microspheres for improved drug delivery. U. S. Patent number US 6,207,197 B1; 2001.
73. Margel S. Metal-coated polyaldehyde microspheres, U. S. Patent Number US 4,624,923; 1986.
74. Li S, Dynan WS, Wicks G, Serkiz S. Porous wall hollow glass microspheres as carrier for biomolecules. U. S. Patent Number US 8,535,725 B2; 2013.
75. Mathiowitz E, Chickering D, Jacob JS. Bioadhesive microspheres and their use as drug delivery and imaging, Patent number US 6,235,313 B1; 2001.
76. Walt DR, Mandal TK, Fleming MS. Polymeric microspheres, U. S. Patent Number US 6,720,007 B2; 2004.
77. Billot GB, Teichner MM. Process for preparing microspheres for prolonged release of the LHRH hormone and its analogues, microspheres and formulations obtained, U. S. Patent number US 5,540,937; 1996.
78. Brown LR. Production of microspheres, patent number US 7,374,782 B2; 2008.
79. Barrow WW, Barrow EL, Quenelle DC, Winchester GA, Staas JK. Compositions and methods for treating intracellular infections. U. S. Patent number-US 6,264,991 B1; 2001.
80. Wani SUD, Gangadharappa HV, Ashish NP. Formulation, development and characterization of drug delivery systems based telmisartan encapsulated in silk fibroin nanosphere’s. Int J Appl Pharm 2019;11:247-54.
81. Wani SUD, Gangadharappa HV. Silk fibroin based drug delivery applications: promises and challenge. Curr Drug Targets 2018;19:1177-90.
2. Ganesan P, Jonson AJD. Review on microspheres. Am J Drug Discovery Dev 2014;4:153-79.
3. Whelehan M, Marison IW. Microencapsulation using vibrating technology. J Microencapsul 2011;28:669–88.
4. Yang Q, Forrest L. Drug delivery to the lymphatic system. In: Wang B, Hu L, Siahaan TJ. editors. Drug Delivery Principles and Applications. 2nd ed. Hoboken: John Wiley and Sons Inc; 2016. p. 503-48.
5. Desai T, Shea LD. Advances in islet encapsulation technologies. Nat Publ Gr 2016;16:338–50.
6. Virmani T, Gupta J. Pharmaceutical application of microspheres: an approach for the treatment of various diseases. Int J Pharm Sci Res 2017;8:3252-60.
7. Prajapati VD, Jani GK, Kapadia JR. Current knowledge on biodegradable microspheres in drug delivery. Expert Opin Drug Delivery 2015;12:1283–99.
8. Doty AC. Mechanistic analysis of in vivo and in vitro drug release from PLGA Microspheres. Ph. D. Thesis, University of Michigan, Ann Arbor, ML, USA; 2015.
9. Lengyel M, Kallai Sazabo, N Microparticles. Microspheres and microcapsules for advanced drug delivery. Sci Pharm 2019;87:1-31.
10. Senthil A. Mucoadhesive microspheres. Int J Pharm Res Ayurveda Pharm 2011;2:55-9.
11. Lohani A, Chaudhary GP. Mucoadhesive microspheres: a novel approach to increase gastroretention. Chron Young Sci 2012;3:121-8.
12. Deshmukh MT, Mohite SK. Preparation and evaluation of mucoadhesive microsphere of fluoxitine HCL. Int J Pharm Sci Res 2017;8:3776-85.
13. Singh I, Kamboj S, Rana V. Quality by design based fabrication of iron oxide induced mucoadhesive microspheres for enhanced bioavalibility of cinnarizine. Curr Drug Delivery 2017;14:1154–69.
14. Farah FH. Magnetic microsphers: a noval drug delivery system. J Anal Pharm Res 2016;3:00067.
15. Kakar S, Batra D, Singh R, Nautiyal U. Magnetic microspheres as magical novel drug delivery system: a review. J Acute Disease 2013;2:1-12.
16. Kawatra M, Jain U, Ramana J. Recent advances in floating microspheres as gastroretentive drug delivery system: a review. Int J Recent Adv Pharm Res 2012;2:5-23.
17. Mukund JY, Kantilal BR, Sudhakar RN. Floating microspheres: a review. Braz J Pharm Sci 2012;48:17-30.
18. Bhadouriya P, Kumar M, Pathak K. Floating microspheres: to prolong the gastric retention time in stomach. Curr Drug Delivery 2012;9:315-24.
19. Negi M, Shukla VK, Easwari TS. Overview on recent researches on floating microspheres. J Pharm Biosci 2014;2:25-33.
20. Sinha VR, Goyel V, Trehan A. Radioactive microspheres in therapeutics. Pharmazie 2004;59:419-26.
21. Hafeli U. Radioactive microspheres for medical applications. In: De Cuyper M, Bulte JWM. editors. Physics and Chemistry Basis of Biotechnology. Focus on Biotechnology. Netherlands: Kluwer Academic Publisher; 2001. p. 213-48.
22. Wang SJ, Lin WY, Chen MN, Hsieh BT, Shen LH, Tsai ZT, et al. Rhenium-188 microspheres: a new radiation synovectomy agent. Nucl Med Commun 1998;19:427–33.
23. Kennedy AS. Radioactive microspheres for liver cancers. US Oncol Rev 2005;1:25-8.
24. Davis SS, Illum L. Polymeric microspheres as drug carriers. Biomaterials 1988;9:111-2, IN5, 113-5.
25. Prasanth VV, Moy AC, Mathew S, Rinku M. Microspheres-an overview. Int J Res Pharm Biomed Sci 2011;2:332-8.
26. Saralidze K, Koole LH, Knetsch MLW. Polymeric microspheres for medical applications. Materials (Basel) 2010;3:3537–64.
27. Patel NR, Patel DA, Bharadia PD, Pandya VM, Modi D. Microsphere as novel drug delivery. Int J Pharm Life Sci 2011;2:992-7.
28. Pavan KB, Chandiran IS, Bhavya B, Sindhuri M. Microparticulate drug delivery system: a review. Indian J Pharm Sci Res 2011;1:19-37.
29. Sinha VR, Singla AK, Wadhawan S. Chitosan microspheres as a potential carrier for drugs. Int J Pharm 2004;274:1–33.
30. Mokhtare B, Cetin M, Ozakar RS, Bayrakceken H. Preparation of metformin HCl-loaded chitosan microspheres and in vitro characterization studies. Hacettepe University J Faculty Pharm 2015;35:74-86.
31. Sinha VR, Bansal K, Kaushik R. Polycaprolactone microspheres and nanosphere’s. Int J Pharm 2004;278:1–23.
32. Jain NK. Controlled and novel drug delivery. 4th Ed. New Delhi: CBS Publishers; 2006. p. 236-7.
33. Gohel MC, Parikh RK, Nagori SA, Gandhi AV, Shroff MS, Patel PK, et al. A spray drying a review. Pharm Rev 2009;7;2-23.
34. Parikh D. Spray drying as a granulation technique. In: Handbook of Pharmaceutical Granulation Technology, Drugs and the Pharmaceutical Sciences. New York: Marcel Dekker; 1997. p. 75-96.
35. Swarbrick BJ. Spray drying and spray congealing of pharmaceuticals. In: Encyclopedia of Pharmaceutical Technology. New York Marcel Dekker; 1992. p. 207-21.
36. Sinha VR, Bansal K, Kaushik R. Polycaprolactone microspheres and nanosphere’s. Int J Pharm 2004;278:1–23.
37. He P, Davis SS, Illum L. Chitosan microspheres prepared by spray drying. Int J Pharm 1999;187:53–65.
38. Christina E. Prepration of microspheres of diclofenac sodium by ionotropic gelation technique. Int J Pharm Pharm Sci 2012;5:228-31.
39. McGinity JW, O'Donnell PB. Preparation of microspheres by the solvent evaporation technique. Adv Drug Delivery Rev 1997;28:25-42.
40. Sudhamani T, Reddy N, Ravi Kumar V, Revathi R, Ganesan V. Preparation and evaluation of ethyl cellulose microspheres of ibuprofen for sustained drug delivery. Int J Pharm Res Dev 2010;2:119-25.
41. Merkel HP, Speister P. Preparation and in vitro evaluation of microspheres using cellulose acetate phthalate. J Pharm Sci 1973;62:1444-8.
42. Rahman M, Islam M, Sharmin N, Chowdhury J, Jalil R. Preparation and evaluation of cellulose acetate phthalate and ethyl cellulose-based microcapsules of diclofenac sodium using emulsification and solvent evaporation method. Dhaka University J Pharm Sci 2010;9:39-46.
43. Chaturvedi K, Kulkarni AR, Aminabhavi TM. Blend microspheres of poly(3-hydroxybutyrate) and cellulose acetate phthalate for colon delivery of 5-fluorouracil. Ind Eng Chem Res 2011;50:10414-23.
44. Beyger JW, Nair JG. Some factors affecting the microencapsulation of pharmaceuticals with cellulose acetate phthalate. J Pharm Sci 1986;75:573-8.
45. Farid DJ, Nokhodchi A. Dissolution of compacted aspirin microcapsules. Ind J Pharm Sci 1991;53:222-3.
46. Maharaji I, Nairn JG, Cambell JB. Simple rapid method for the preparation of enteric-coated microcapsules. J Pharm Sci 1984;73:39-42.
47. Lin CY, Lin SJ, Yang YC, Wang DY, Cheng HF, Yeh MK. Biodegradable polymeric microsphere-based vaccines and their applications in infectious diseases. Hum Vaccin Immunother 2015;11:650-6.
48. Kohn J, Niemi SM, Albert EC, Murphy JC, Langer RS, Fox JG. Single-step immunization using a controlled release, biodegradable polymer with sustained adjuvant activity. J Immunol Methods 1986;95:31-7.
49. Gupta RK, Singh M, O'Hagan DT. Poly(lactide-co-glycolide) microparticles for the development of single-dose controlled-release vaccines. Adv Drug Delivery Rev 1998;32:225-46.
50. Nellore RV, Pande PG, Young D, Bhagat HR. Evaluation of biodegradable microspheres as vaccine adjuvant for Hepatitis B surface antigen. J Parenteral Sci Tech 1992;46:176-80.
51. Desai KG, Schwendeman SP. Active self-healing encapsulation of vaccine antigens in PLGA microspheres. J Controlled Release 2013;165:62-74.
52. Cui Y, Cui P, Chen B, Li S, Guan H. Monoclonal antibodies: formulations of marketed products and recent advances in novel delivery system. Drug Dev Ind Pharm 2017;43:519-30
53. Sailaja AK, Anusha K, Jyothika M. Biomedical applications of microspheres. J Modern Drug Discovery Drug Delivery Res 2015;4:1-5.
54. Adamson P, Wilde T, Dobrzynski E, Sychterz C, Polsky R, Kurali E, et al. Single ocular injection of a sustained-release anti-VEGF delivers 6 mo pharmacokinetics and efficacy in a primate laser CNV model. J Controlled Release 2016;244:1–13.
55. Stern M, Ulrich K, Geddes DM, Alton EWFW. Poly (D, L-lactide-co-glycolide)/DNA microspheres to facilitate prolonged transgene expression in airway epithelium in vitro, ex vivo and in vivo. Gene Ther 2003;10:1282-8.
56. Liu W, Borrell MA, Venerus DC, Mieler WF, Kang Mieler JJ. Characterization of biodegradable microsphere-hydrogel ocular drug delivery system for controlled and extended-release of ranibizumab. Curr Eye Res 2018;44:264-74.
57. Lubben IMVD, Kersten G, Fretz MM, Beuvery C, Verhoef JC, Junginger HE. Chitosan microparticles for mucosal vaccination against diphtheria: oral and nasal efficacy studies in mice. Vaccine 2003;21:1400-8.
58. Rathananand M, Kumar DS, Shirwaikar A, Kumar R, Kumar S, Prasad RS. Preparation of mucoadhesive microspheres for nasal delivery by spray drying. Indian J Pharm Sci 2007;69:651-7.
59. Pereswetoff Morath L. Microspheres as nasal drug delivery systems. Adv Drug Delivery Rev Adv Drug Delivery Rev 1998;29:185-94.
60. Nigam J, Pandey P, Mishra MK. Formulation and evaluation of anti-emetic microspheres for nasal drug delivery system. Indian J Novel Drug Delivery 2017;9:44-53.
61. Saez VC, Hernandez JR, Peniche C. Microspheres as delivery systems for the controlled release of peptides and proteins. Biotecnol Aplicada 2007;24:108-16.
62. Ma G. Microencapsulation of protein drugs for drug delivery: strategy, preparation, and applications. J Controlled Release 2014;193:324-40.
63. Thundimadathil J. Peptide therapeutics: strategy and tactics for chemistry manufacturing and controls. In: Srivastava V. editor. Formulations of microspheres and nanoparticles for peptide delivery. 1st edition. Cryodon: Royal Society of Chemistry; 2019. p. 503-30.
64. Rajput MS, Agrawal P. Microspheres in cancer therapy. Indian J Cancer 2010;47:458-68.
65. Midha K, Nagpal M, Arora S. Microspheres: a recent update. Int J Recent Sci Res 2015;6:5859-67.
66. Singh A, Sharma PK, Malviya R. Sustained drug delivery using mucoadhesive microspheres: the basic concept, preparation methods and recent patents. Recent Patents Nanomed 2012;2:62-77.
67. Mishra N, Goyal AK, Khatri K, Vaidya B. Biodegradable polymer based particulate carrier(s) for the delivery of proteins and peptides. Anti-Inflammatory Anti-Allergy Agents Med Chem 2008;7:240-51.
68. Jin T, Hu Z, Yuan W. Microspheres for controlled-or sustained-release delivery of therapeutics. U. S. Patent number-US9381159B2; 2016.
69. Lewis AL, Tang Y, Stratford PW. Microspheres for treatment of brain tumors, US 8,691,791 B2; 2014.
70. Singh A, Singh S, Puthli S, Tandale R. Programmable buoyant delivery technology. U. S. Patent number US 8,277,843 B2; 2012.
71. Chandler DJ, Austin Bedre J. Magnetic microspheres for use in fluorescence-based applications. U. S. Patent Number US 7,718,262 B2; 2010.
72. Ilum L, Ping H. Gastroretentive controlled-release microspheres for improved drug delivery. U. S. Patent number US 6,207,197 B1; 2001.
73. Margel S. Metal-coated polyaldehyde microspheres, U. S. Patent Number US 4,624,923; 1986.
74. Li S, Dynan WS, Wicks G, Serkiz S. Porous wall hollow glass microspheres as carrier for biomolecules. U. S. Patent Number US 8,535,725 B2; 2013.
75. Mathiowitz E, Chickering D, Jacob JS. Bioadhesive microspheres and their use as drug delivery and imaging, Patent number US 6,235,313 B1; 2001.
76. Walt DR, Mandal TK, Fleming MS. Polymeric microspheres, U. S. Patent Number US 6,720,007 B2; 2004.
77. Billot GB, Teichner MM. Process for preparing microspheres for prolonged release of the LHRH hormone and its analogues, microspheres and formulations obtained, U. S. Patent number US 5,540,937; 1996.
78. Brown LR. Production of microspheres, patent number US 7,374,782 B2; 2008.
79. Barrow WW, Barrow EL, Quenelle DC, Winchester GA, Staas JK. Compositions and methods for treating intracellular infections. U. S. Patent number-US 6,264,991 B1; 2001.
80. Wani SUD, Gangadharappa HV, Ashish NP. Formulation, development and characterization of drug delivery systems based telmisartan encapsulated in silk fibroin nanosphere’s. Int J Appl Pharm 2019;11:247-54.
81. Wani SUD, Gangadharappa HV. Silk fibroin based drug delivery applications: promises and challenge. Curr Drug Targets 2018;19:1177-90.
Published
15-05-2020
How to Cite
KAKKAR, V., S. U. D. WANI, S. P. GAUTAM, and Z. L. QADRIE. “ROLE OF MICROSPHERES IN NOVEL DRUG DELIVERY SYSTEMS: PREPARATION METHODS AND APPLICATIONS”. International Journal of Current Pharmaceutical Research, vol. 12, no. 3, May 2020, pp. 10-15, doi:10.22159/ijcpr.2020v12i3.38326.
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