STAVUDINE LOADED BIODEGRADABLE POLYMERIC MICROSPHERES AS A DEPOT SYSTEM FOR PARENTERAL DELIVERY
Abstract
Injectable biodegradable polymeric microspheres of Stavudine were prepared using different viscosity grades of PLGA 50:50 (RESOMER® 504H and RESOMER® 502H) by solvent evaporation technique with different drug/polymer ratios. Tailored release of Stavudine facilitates reduction in symptoms of HIV infection and delay AIDS progression by reducing viral load to undetectable levels for extended period of time. The influence of formulation variables on microparticle characteristics like polymer type and concentration, vehicle type, polymer solution/vehicle volume ratio, surfactant concentration and drug to polymer ratios were evaluated. Microspheres were evaluated for yield, entrapment efficiency, particle size and in-vitro release behavior as well as characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), residual solvent analysis and confocal laser scanning microscopy (CLSM). Microspheres showed excellent surface topography with uniform distribution and structural integrity of the drug having the entrapment efficiency of 90.96 ± 1.09 and mean particle diameter below 65μm. Drug release kinetics data were obtained from various kinetic models and best explained by “Korsmeyer-Peppas equation” for both the polymers which depicted that drug release mechanism is anomalous transport, i.e. diffusion as well as polymer relaxation. Drug release from microspheres exhibited the characteristic release pattern of a monolithic matrix system with 90-100% drug release in 6-8 weeks demonstrating the feasibility of prolonged delivery of Stavudine using biodegradable microspheres for parenteral depot system.
Keywords:
HIV, Microspheres, Stavudine, Biodegradable Polymer, Prolonged Release, Parenteral deliveryDOI
https://doi.org/10.25004/IJPSDR.2013.050101References
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24. Dinarvand R, Moghadam SH, Mohammadyari-Fard L, Atyabi F. Preparation of Biodegradable Microspheres and Mtrix Devices Containing Naltrexone. AAPS Pharm Sci Tech. 2003; 4: 1-10.
25. Kim BK, Hwang SJ, Park JB, Park HJ. Characteristics of felodipine loaded poly (ε-caprolactone) microspheres. J. Microencapsul. 2005; 22: 193-203.
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27. Amy G, Schwendeman SP. Acidic Microclimate pH Distribution in PLGA Microspheres Monitored by Confocal Laser Scanning Microscopy. Pharm. Res. 2008; 25: 2041-2052.
28. Pygall SR, Whetstone J, Timmins P, Melia CD. Pharmaceutical applications of confocal laser scanning microscopy: The physical characterisation of pharmaceutical systems. Ad Drug Del Reviews. 2007; 59: 1434–1452.
29. Sinha VR, Trehan A. Biodegradable microspheres for protein delivery. J Control Release. 2003; 90: 261-280.
30. Burgess DJ, Hickey AJ. Microsphere technology and applications. In: J Swarbrick, JC Boylan, eds. Encyclopedia of Pharmaceutical Technology. New York, NY: Marcel Dekker, 1994, pp. 1-29.
31. Gandhi RB, Bogardus JB, Bugay DE, Perrone RK, Kaplan MA. Pharmaceutical relationships of three solid state forms of stavudine. International J. Pharm. 2000; 201: 221-237.
32. D'Souza SS, DeLuca PP. Methods to Assess in-vitro drug release from injectable polymeric particulate systems. Pharm Res. 2006; 23: 460–74.
33. D’Souza SS, Faraj JA, DeLuca PP. A model-dependent approach to correlate accelerated with real-time release from biodegradable microspheres. AAPS Pharm Sci Tech 2005; 6: 553-564.
2. Huthoff H, Malim MH. Identification of amino acid residues in apobec3g required for regulation by human immunodeficiency virus type 1 vif and virion encapsidation. J Virol. 2007; 81: 3807-3815.
3. Broder S. The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic. Antiviral Res. 2010; 85: 1-18.
4. Greenberg M, Cammack N, Salgo M, Smiley L. HIV fusion and its inhibition in antiretroviral therapy. Rev Med Virol. 2004; 14: 321-337.
5. Chinen J, Shearer WT. Secondary immunodeficiency, including HIV infection. J. Allergy Clin. Immunol. 2008; 388-392.
6. Jamjian MC, McNicholl IR. Enfuvirtide: first fusion inhibitor for treatment of HIV infection. Am J Health Syst Pharm. 2004; 61: 1242.
7. Naidoo P. Barriers to HIV care and treatment by doctors: a review of the literature, SA Fam. Pract. 2006; 48: 53.
8. Girard MP, Osmanov SK, Kieny MP. A review of vaccine research and development: the human immunodeficiency virus (HIV). Vaccine 2006; 24: 4062-4081.
9. Stebbing J, Nelson M, Orkin C, Mandalia S, Bower M, Pozniak A, Gazzard BA. Randomized trial to investigate the recycling of stavudine and didanosine with and without hydroxyurea in salvage therapy. J. Antimicrobial Chemotherapy. 2004; 53: 501-505.
10. Wallace MR, Miller LK, Haze B, Olson PE. Clinical Experience with Stavudine as Salvage Therapy in Patients with Advanced HIV Disease. J. Acquired Immune Deficiency Syndromes and Human Retrovirology 1996; 13: 96-97.
11. Tamilvanan S, Babu VR, Kannan K, Basu SK. Manufacturing techniques and excipients used during the design of biodegradable polymer-based microspheres containing therapeutic peptide/protein for parenteral controlled drug delivery. PDA J Pharm Sci Technol. 2008; 62: 125-54.
12. Hickey T, Kreutzer D, Burgess DJ, Moussy F. Dexamethasone/PLGA microspheres for continuous delivery of an anti-inflammatory drug for implantable medical devices. Biomaterials. 2002; 23: 1649-1656.
13. Burgess DJ, Hussain AS, Ingallinera TS, Chen ML. Assuring quality and performance of sustained and controlled release parenterals: workshop report. AAPS Pharm Sci. 2002; 4: 7.
14. Okada H, Doken Y, Ogawa Y, Toguchi H. Preparation of three-month injectable microspheres of leuprorelin acetate using biodegradable polymers. Pharm Res. 1994; 11:1143-1147.
15. Kane JM, Eerdekens M, Lindenmayer JP, Keith SJ, Lesem M, Karcher K. Long-acting injectable Risperidone: efficacy and safety of the first long-acting atypical antipsychotic. Am J Psychiatry. 2003; 160:1125-1132.
16. Woo BH, Dani BA, Jiang G, Thanoo BC, DeLuca PP. In-vitro characterization and in-vivo testosterone suppression of 6-month release poly (D, L-lactide) leuprolide microspheres. Pharm Res. 2002; 19: 546-550.
17. Kostanski JW, Thanoo BC, DeLuca PP. Preparation, characterization, and in vitro evaluation of 1- and 4-month controlled release orntide PLA and PLGA microspheres. Pharm Dev Technol. 2000; 5: 585-596.
18. Srivastava S, Sinha VR. Development and Evaluation of Stavudine Loaded Injectable Polymeric Particulate Systems, Current drug delivery. 2011; 8: 436-447.
19. Sinha VR, Trehan A. Formulation, Characterization, and Evaluation of Ketorolac Tromethamine-Loaded Biodegradable Microspheres. Drug Delivery. 2005; 12: 133-139.
20. Lee JH, Park TG, Choi HK. Effect of formulation and processing variables on the characteristics of microspheres for water soluble drugs prepared by w/o/o double emulsion solvent diffusion method. Int. J. Pharm. 2000; 196: 75-83.
21. Ito F, Fujimori H, Makino K. Factors affecting the loading efficiency of water-soluble drugs in PLGA microspheres. Colloids and Surfaces B: Biointerfaces. 2008; 61: 25-29.
22. Jain SA, Chauk DS, Mahajan HS, Tekade AR, Gattani SG. Formulation and evaluation of nasal Mucoadhesive microspheres of Sumatriptan succinate. J. Microencapsul. 2009; 1: 1-11.
23. Cui F, Cun D, Tao A, Yang M, Zhao M, Guan Y. Preparation and characterization of melittin-loaded poly (dl-lactic acid) or poly (dl-lactic-co-glycolic acid) microspheres made by the double emulsion method. J. Control Rel. 2005; 107: 310-319.
24. Dinarvand R, Moghadam SH, Mohammadyari-Fard L, Atyabi F. Preparation of Biodegradable Microspheres and Mtrix Devices Containing Naltrexone. AAPS Pharm Sci Tech. 2003; 4: 1-10.
25. Kim BK, Hwang SJ, Park JB, Park HJ. Characteristics of felodipine loaded poly (ε-caprolactone) microspheres. J. Microencapsul. 2005; 22: 193-203.
26. Peltonen L, Aitta J, Hyvonen S, Karjalainen M, Hirvonen J. Improved entrapment efficiency of hydrophilic drug substance during nanoprecipitation of poly (l) lactide nanoparticles. AAPS Pharm. Sci. Tech. 2004; 5: 16-21.
27. Amy G, Schwendeman SP. Acidic Microclimate pH Distribution in PLGA Microspheres Monitored by Confocal Laser Scanning Microscopy. Pharm. Res. 2008; 25: 2041-2052.
28. Pygall SR, Whetstone J, Timmins P, Melia CD. Pharmaceutical applications of confocal laser scanning microscopy: The physical characterisation of pharmaceutical systems. Ad Drug Del Reviews. 2007; 59: 1434–1452.
29. Sinha VR, Trehan A. Biodegradable microspheres for protein delivery. J Control Release. 2003; 90: 261-280.
30. Burgess DJ, Hickey AJ. Microsphere technology and applications. In: J Swarbrick, JC Boylan, eds. Encyclopedia of Pharmaceutical Technology. New York, NY: Marcel Dekker, 1994, pp. 1-29.
31. Gandhi RB, Bogardus JB, Bugay DE, Perrone RK, Kaplan MA. Pharmaceutical relationships of three solid state forms of stavudine. International J. Pharm. 2000; 201: 221-237.
32. D'Souza SS, DeLuca PP. Methods to Assess in-vitro drug release from injectable polymeric particulate systems. Pharm Res. 2006; 23: 460–74.
33. D’Souza SS, Faraj JA, DeLuca PP. A model-dependent approach to correlate accelerated with real-time release from biodegradable microspheres. AAPS Pharm Sci Tech 2005; 6: 553-564.
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01-01-2013
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“STAVUDINE LOADED BIODEGRADABLE POLYMERIC MICROSPHERES AS A DEPOT SYSTEM FOR PARENTERAL DELIVERY”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 5, no. 1, Jan. 2013, pp. 01-13, https://doi.org/10.25004/IJPSDR.2013.050101.
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How to Cite
“STAVUDINE LOADED BIODEGRADABLE POLYMERIC MICROSPHERES AS A DEPOT SYSTEM FOR PARENTERAL DELIVERY”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 5, no. 1, Jan. 2013, pp. 01-13, https://doi.org/10.25004/IJPSDR.2013.050101.
