INFLUENCE OF FORMULATION COMPONENTS ON AEROSOLIZATION PROPERTIES OF ISONIAZID LOADED CHITOSAN MICROSPHERES
Abstract
The objective of the present study was to prepare microspheres with small size and good sphericity by spray drying technology using Isoniazid (INH) as model drug, chitosan as encapsulating polymer; lactose and L Leucine as bulking and dispersing agent respectively. Influence of formulation components on physical properties and aerosol performance were studied. The spray dried powders obtained were characterized for morphological characteristics, compatibility using scanning electron microscopy and Differential Scanning calorimetery respectively. Tapped density; bulk density and aerosol properties like Fine particle fraction, mass median aerodynamic diameter etc were also evaluated. The smooth microspheres with particle size ranging between 4 to 6 µm were obtained. The drug content of chitosan microspheres loaded with Isoniazid were in the range of 88 % to 108 %. The drug release studies showed that more than 90% of drug released from the chitosan microsphere matrix within one hour. The fine particle fraction observed between 55 to 67 % which indicate good lung deposition. Results of Fine particle fraction also revealed addition of L Leucine found to enhance powder dispersibility.
Keywords:
Isoniazid, dry powder, L Leucine, Andersen cascade impactor, fin particle fraction.DOI
https://doi.org/10.25004/IJPSDR.2011.030405References
1. Lenzer J. Inhaled insulin is approved in Europe and United States. Br Med J. 2006; 332:21.
2. Chew YK and Chan HK. Use of solid corrugated particles to enhance powder aerosol performance. Pharm Res. 2001; 18:1570-1577.
3. Chan HK, Clark A, Gonda I, Mumenthaler M, Hsu C. Spray dried powders and powder blends of recombinant human deoxyribonuclease (rhDNase) for aerosol delivery. Pharm Res. 1997; 14:431-437.
4. Srichana T, Martin GP, Marriott C. On the relationship between drug and carrier deposition from dry powder inhalers in vitro. Int J Pharm. 1998; 167:13-23.
5. Lucas P, Andersen K, Potter UJ, Staniforth JN. Enhancement of small particle size dry powder aerosol formulations using an ultra low density additive. Pharm Res. 1999; 16:1643-1647.
6. Young PM, Cocconi D, Colombo P, Bettini R, Price R, Steele DF, Tobyn MJ. Characterization of a surface modified dry powder inhalation carrier prepared by ‘‘particle smoothing’’. J Pharm Pharmacol. 2002; 54:1339-1344.
7. Edwards DA, Hanes J, Caponetti G, Hrkach J, Ben-Jebria A, Eskew ML, Mintzes J, Deaver D, Lotan N, Langer R. Large porous particles for pulmonary drug delivery. Science 1997; 276:1868-1871.
8. Larhrib H, Martin GP, Marriott C, Prime D. The influence of carrier and drug morphology on drug delivery from dry powder formulations. Int J Pharm. 2003; 257: 283-296.
9. Giovagnoli, Blasi P, Schoubben A, Rossi C, Ricci M. Preparation of large porous biodegradable microspheres by using a simple double-emulsion method for capreomycin sulfate pulmonary delivery. Int J Pharm. 2007; 333:103-111.
10. Steckel H, Brandes HG. A novel spray-drying technique to produce low density particles for pulmonary delivery. Int J Pharm. 2004; 278:187-195.
11. Rasenack N, Muller BW. Micron-size drug particles: common and novel micronization techniques. Pharm Dev Technol. 2004; 9:1-13.
12. Li HY, Neill H, Innocent R, Seville P, Williamson I, Birchall JC. Enhanced dispersibility and deposition of spray-dried powders for pulmonary gene therapy. J Drug Target. 2003; 11:425-432.
13. Li HY, Seville PC, Williamson IJ, Birchall JC. The use of amino acids to enhance the aerosolisation of spray-dried powders for pulmonary gene therapy. J Gene Med. 2005; 7:343-353.
14. Rabbani NR, Seville PC. The influence of formulation components on the aerosolisation properties of spray-dried powders. J Control Rel. 2005; 110:130-140.
15. Surendrakumar K, Martyn GP, Hodgers EC, Jansen M, Blair JA. Sustained release of insulin from sodium hyaluronate based dry powder formulations after pulmonary delivery to beagle dogs. J Control Rel 2003; 91:385-394.
16. Cook RO, Pannu RK, Kellaway IW. Novel sustained release microspheres for pulmonary drug delivery. J Control Rel. 2005; 104:79-90.
17. Taylor MK, Hickey AJ, Vanoort M. Manufacture, characterization, and pharmacodynamic evaluation of engineered ipratropium bromide particles. Pharm Dev Technol. 2006; 11:321-336.
18. Pavanetto F, Genta I, Giunchedi P, Conti B, Conte U. Spray-dried albumin microspheres for the intra-articular delivery of dexamethasone. Journal of Microencapsulation. 1994; 11:445-454.
19. Okamoto H, Nishida S, Todo H, Sakakura Y, Iida K, Danjo K. Pulmonary gene delivery by chitosan-pDNA complex powder prepared by a supercritical carbon dioxide process. J Pharm Sci. 2003; 92:371-380.
20. Williams III RO, Barron MK, Alonso MJ, Remunan-Lopez C. Investigation of a pMDI system containing chitosan microspheres and P134a. Int J Pharm. 1998; 174 :209-222.
21. Lueben HL, Rentel CO, Kotze AF, Lehr CM, de Boer AG, Verhoel JC. Mucoadhesive polymers in peroral peptide drug delivery. IV. Polycarbophil and chitosan are potent enhancers of peptide transport across intestinal mucosae in vitro. Int J Pharm. 1997; 45:15-23.
22. Sinha VR, Singla AK, Wadhawan S, Kaushik R, Kumaria R, Bansal K, Dhawan S. Chitosan microspheres as a potential carrier for drugs. Int J Pharm. 2004; 274:1-33.
23. De Villiers MM. Powder flow and compressibility, in: TK Ghosh, BR Jasti (Eds.), Theory and Practice of Contemporary Pharmaceutics, CRC Press, Boca Raton, Florida, USA, 2005.
24. Bosquillon C, Preat V, Vanbever R. Pulmonary delivery of growth hormone using dry powders and visualization of its local fate in rats. J. Control Release. 2004; 96:233-244.
25. He P, Davis SS, Illum L. Chitosan microspheres prepared by spray drying Int J Pharm. 1999; 187:53–65.
26. Giunchedi P, Genta I, Conti B, Muzzarelli RA, Conte U. Preparation and characterization of ampicillin loaded methylpyrrolidinone chitosan and chitosan microspheres. Biomaterials. 1998; 19:157-161.
27. Russo P, Sacchetti C, Pasquali I, Bettini R, Massimo G, Colombo P, Rossi A. Primary microparticles and agglomerates of morphine for nasal insufflation. J Pharm Sci. 2006; 95:2553-2561.
28. Hardy JG, Chadwick TS. Sustained release drug delivery to the lungs: an option for the future. Clin Pharmacokinet. 2000; 39:1-4.
29. Filipovic-Grcic J, Perissutti B, Moneghini M, Voinovich D, Martinac A, Jalsenjak I. Spray-dried carbamazepine-loaded chitosan and HPMC microspheres: preparation and characterization. J Pharm Pharmacol. 2003; 55:921-931.
30. Corrigan DO, Healy AM, Corrigan OI. Preparation and release of salbutamol from chitosan and chitosan co-spray dried compacts and multiparticulates. Eur J Pharm Biopharm. 2006; 62:295-305.
31. Li HY, Neill H, Innocent R, Seville P, Williamson I, Birchall JC. Enhanced dispersibility and deposition of spray-dried powders for pulmonary gene therapy. J. Drug Target. 2003; 11:425-432.
32. Li HY, Seville PC, Williamson IJ, Birchall JC. The use of amino acids to enhance the aerosolisation of spray-dried powders for pulmonary gene therapy. J Gene Med. 2005; 7: 343-353.
33. Rabbani NR, Seville PC. The influence of formulation components on the aerosolisation properties of spray-dried powders. J Control Rel. 2005; 110:130-140.
34. Bosquillon C, Preat V, Vanbever R. Pulmonary delivery of growth hormone using dry powders and visualization of its local fate in rats. J Control Rel. 2004; 96:233-244.
35. Wolfenden R, Andersson L, Cullis P, Southgate C. Affinities of amino acid side chains for solvent water. Biochemistry. 1981; 20:849-855.
36. Black SD, Mould DR. Amino acid scale: hydrophobicity of physiological L-alpha amino acids. Anal Biochem. 1991; 193:72-82.
37. Gliniski J, Chavepeyer G, Platten JK. Surface properties of aqueous solutions of L-L Leucine. Biophys. Chem. 2000; 84:99-103.
38. Columbano A, Buckton G, Wikeley P. Characterization of surface modified salbutamol sulphate –alkylpolyglycoside microparticles prepared by spray drying. Int. J. Pharm. 2003; 253:61-70.
39. Li H-Y, Birchall J. Chitosan-modified dry powder formulations for pulmonary gene delivery. Pharm Res. 2006; 23:941-950.
2. Chew YK and Chan HK. Use of solid corrugated particles to enhance powder aerosol performance. Pharm Res. 2001; 18:1570-1577.
3. Chan HK, Clark A, Gonda I, Mumenthaler M, Hsu C. Spray dried powders and powder blends of recombinant human deoxyribonuclease (rhDNase) for aerosol delivery. Pharm Res. 1997; 14:431-437.
4. Srichana T, Martin GP, Marriott C. On the relationship between drug and carrier deposition from dry powder inhalers in vitro. Int J Pharm. 1998; 167:13-23.
5. Lucas P, Andersen K, Potter UJ, Staniforth JN. Enhancement of small particle size dry powder aerosol formulations using an ultra low density additive. Pharm Res. 1999; 16:1643-1647.
6. Young PM, Cocconi D, Colombo P, Bettini R, Price R, Steele DF, Tobyn MJ. Characterization of a surface modified dry powder inhalation carrier prepared by ‘‘particle smoothing’’. J Pharm Pharmacol. 2002; 54:1339-1344.
7. Edwards DA, Hanes J, Caponetti G, Hrkach J, Ben-Jebria A, Eskew ML, Mintzes J, Deaver D, Lotan N, Langer R. Large porous particles for pulmonary drug delivery. Science 1997; 276:1868-1871.
8. Larhrib H, Martin GP, Marriott C, Prime D. The influence of carrier and drug morphology on drug delivery from dry powder formulations. Int J Pharm. 2003; 257: 283-296.
9. Giovagnoli, Blasi P, Schoubben A, Rossi C, Ricci M. Preparation of large porous biodegradable microspheres by using a simple double-emulsion method for capreomycin sulfate pulmonary delivery. Int J Pharm. 2007; 333:103-111.
10. Steckel H, Brandes HG. A novel spray-drying technique to produce low density particles for pulmonary delivery. Int J Pharm. 2004; 278:187-195.
11. Rasenack N, Muller BW. Micron-size drug particles: common and novel micronization techniques. Pharm Dev Technol. 2004; 9:1-13.
12. Li HY, Neill H, Innocent R, Seville P, Williamson I, Birchall JC. Enhanced dispersibility and deposition of spray-dried powders for pulmonary gene therapy. J Drug Target. 2003; 11:425-432.
13. Li HY, Seville PC, Williamson IJ, Birchall JC. The use of amino acids to enhance the aerosolisation of spray-dried powders for pulmonary gene therapy. J Gene Med. 2005; 7:343-353.
14. Rabbani NR, Seville PC. The influence of formulation components on the aerosolisation properties of spray-dried powders. J Control Rel. 2005; 110:130-140.
15. Surendrakumar K, Martyn GP, Hodgers EC, Jansen M, Blair JA. Sustained release of insulin from sodium hyaluronate based dry powder formulations after pulmonary delivery to beagle dogs. J Control Rel 2003; 91:385-394.
16. Cook RO, Pannu RK, Kellaway IW. Novel sustained release microspheres for pulmonary drug delivery. J Control Rel. 2005; 104:79-90.
17. Taylor MK, Hickey AJ, Vanoort M. Manufacture, characterization, and pharmacodynamic evaluation of engineered ipratropium bromide particles. Pharm Dev Technol. 2006; 11:321-336.
18. Pavanetto F, Genta I, Giunchedi P, Conti B, Conte U. Spray-dried albumin microspheres for the intra-articular delivery of dexamethasone. Journal of Microencapsulation. 1994; 11:445-454.
19. Okamoto H, Nishida S, Todo H, Sakakura Y, Iida K, Danjo K. Pulmonary gene delivery by chitosan-pDNA complex powder prepared by a supercritical carbon dioxide process. J Pharm Sci. 2003; 92:371-380.
20. Williams III RO, Barron MK, Alonso MJ, Remunan-Lopez C. Investigation of a pMDI system containing chitosan microspheres and P134a. Int J Pharm. 1998; 174 :209-222.
21. Lueben HL, Rentel CO, Kotze AF, Lehr CM, de Boer AG, Verhoel JC. Mucoadhesive polymers in peroral peptide drug delivery. IV. Polycarbophil and chitosan are potent enhancers of peptide transport across intestinal mucosae in vitro. Int J Pharm. 1997; 45:15-23.
22. Sinha VR, Singla AK, Wadhawan S, Kaushik R, Kumaria R, Bansal K, Dhawan S. Chitosan microspheres as a potential carrier for drugs. Int J Pharm. 2004; 274:1-33.
23. De Villiers MM. Powder flow and compressibility, in: TK Ghosh, BR Jasti (Eds.), Theory and Practice of Contemporary Pharmaceutics, CRC Press, Boca Raton, Florida, USA, 2005.
24. Bosquillon C, Preat V, Vanbever R. Pulmonary delivery of growth hormone using dry powders and visualization of its local fate in rats. J. Control Release. 2004; 96:233-244.
25. He P, Davis SS, Illum L. Chitosan microspheres prepared by spray drying Int J Pharm. 1999; 187:53–65.
26. Giunchedi P, Genta I, Conti B, Muzzarelli RA, Conte U. Preparation and characterization of ampicillin loaded methylpyrrolidinone chitosan and chitosan microspheres. Biomaterials. 1998; 19:157-161.
27. Russo P, Sacchetti C, Pasquali I, Bettini R, Massimo G, Colombo P, Rossi A. Primary microparticles and agglomerates of morphine for nasal insufflation. J Pharm Sci. 2006; 95:2553-2561.
28. Hardy JG, Chadwick TS. Sustained release drug delivery to the lungs: an option for the future. Clin Pharmacokinet. 2000; 39:1-4.
29. Filipovic-Grcic J, Perissutti B, Moneghini M, Voinovich D, Martinac A, Jalsenjak I. Spray-dried carbamazepine-loaded chitosan and HPMC microspheres: preparation and characterization. J Pharm Pharmacol. 2003; 55:921-931.
30. Corrigan DO, Healy AM, Corrigan OI. Preparation and release of salbutamol from chitosan and chitosan co-spray dried compacts and multiparticulates. Eur J Pharm Biopharm. 2006; 62:295-305.
31. Li HY, Neill H, Innocent R, Seville P, Williamson I, Birchall JC. Enhanced dispersibility and deposition of spray-dried powders for pulmonary gene therapy. J. Drug Target. 2003; 11:425-432.
32. Li HY, Seville PC, Williamson IJ, Birchall JC. The use of amino acids to enhance the aerosolisation of spray-dried powders for pulmonary gene therapy. J Gene Med. 2005; 7: 343-353.
33. Rabbani NR, Seville PC. The influence of formulation components on the aerosolisation properties of spray-dried powders. J Control Rel. 2005; 110:130-140.
34. Bosquillon C, Preat V, Vanbever R. Pulmonary delivery of growth hormone using dry powders and visualization of its local fate in rats. J Control Rel. 2004; 96:233-244.
35. Wolfenden R, Andersson L, Cullis P, Southgate C. Affinities of amino acid side chains for solvent water. Biochemistry. 1981; 20:849-855.
36. Black SD, Mould DR. Amino acid scale: hydrophobicity of physiological L-alpha amino acids. Anal Biochem. 1991; 193:72-82.
37. Gliniski J, Chavepeyer G, Platten JK. Surface properties of aqueous solutions of L-L Leucine. Biophys. Chem. 2000; 84:99-103.
38. Columbano A, Buckton G, Wikeley P. Characterization of surface modified salbutamol sulphate –alkylpolyglycoside microparticles prepared by spray drying. Int. J. Pharm. 2003; 253:61-70.
39. Li H-Y, Birchall J. Chitosan-modified dry powder formulations for pulmonary gene delivery. Pharm Res. 2006; 23:941-950.
Published
01-07-2018
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“INFLUENCE OF FORMULATION COMPONENTS ON AEROSOLIZATION PROPERTIES OF ISONIAZID LOADED CHITOSAN MICROSPHERES”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 3, no. 4, July 2018, pp. 297-02, https://doi.org/10.25004/IJPSDR.2011.030405.
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How to Cite
“INFLUENCE OF FORMULATION COMPONENTS ON AEROSOLIZATION PROPERTIES OF ISONIAZID LOADED CHITOSAN MICROSPHERES”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 3, no. 4, July 2018, pp. 297-02, https://doi.org/10.25004/IJPSDR.2011.030405.
