PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
 
AAPS PharmSciTech. 2006 March; 7(1): E79–E88.
Published online 2006 February 10. doi:  10.1208/pt070112
PMCID: PMC2750719

Spray-dried mucoadhesive microspheres: Preparation and transport through nasal cell monolayer

Abstract

The purpose of this research was to prepare spray-dried mucoadhesive microspheres for nasal delivery. Microspheres composed of hydroxypropyl methylcellulose (H), chitosan (CS), carbopol 934P (CP) and various combinations of these mucoadhesive polymers, and maltodextrin (M), colloidal silicon dioxide (A), and propylene glycol (P) as filler and shaper, were prepared by spray-drying technique. Using propranolol HCl as a model drug, microspheres were prepared at loadings exceedings 80% and yields between 24% and 74%. Bulky, free flowing microspheres that had median particle size between 15 and 23 μm were obtained. Their zeta potential was according to the charge of polymer. Adhesion time of mucoadhesive microspheres on isolated pig intestine was ranked, CS>CP: H>CP>H, while the rank order of swelling was CP>CS>H. Increasing the amount of CP in CP[ratio]H formulations increased the percentage of swelling. Infrared (IR) spectra showed no interaction between excipients used except CS with acetic acid. The release of drug from CP and CP[ratio]H microspheres was slower than the release from H and CS microspheres, correlated to their viscosity and swelling. Long lag time from the CP microspheres could be shortened when combined with H. The permeation of drug through nasal cell monolayer corresponded to their release profiles. These microspheres affected the integrity of tight junctions, relative to their swelling and charge of polymer. Cell viability was not affected except from CS microspheres, but recovery could be obtained. In conclusion, spray-dried microspheres of H, CS, CP, and CP[ratio]H could be prepared to deliver drug through nasal cell monolayer via the opening of tight junction without cell damaging.

Keywords: mucoadhesive polymers, spray-dried microspheres, nasal cell monolayer, permeation, cell viability

Full Text

The Full Text of this article is available as a PDF (400K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Vasir JK, Tambwekar K, Garg S. Bioadhesive microspheres as a controlled drug delivery system. Int J Pharm. 2003;255:13–32. doi: 10.1016/S0378-5173(03)00087-5. [PubMed] [Cross Ref]
2. Lim ST, Martin GP, Berry DJ, Brown MB. Preparation and evaluation of the in vitro drug release properties and mucoadhesion of novel microspheres of hyaluronic acid and chitosan. J Control Release. 2000;66:281–292. doi: 10.1016/S0168-3659(99)00285-0. [PubMed] [Cross Ref]
3. Morimoto K, Katsumata H, Yabuta T, et al. Evaluation of gelatin microspheres for nasal and intramuscular administrations of salmon calcitonin. Eur J Pharm Sci. 2001;13:179–185. doi: 10.1016/S0928-0987(01)00094-X. [PubMed] [Cross Ref]
4. Van Der Lubben IM, Van Opdorp FAC, Hengeveld MR, et al. Transport of chitosan microspheres for mucosal vaccine delivery in a human intestinal M-cell model. J Drug Target. 2000;10:449–456. doi: 10.1080/1061186021000038319. [PubMed] [Cross Ref]
5. Ozbas-Turan S, Akbuga J, Aral C. Controlled release of interleukin-2 from chitosan microspheres. J Pharm Sci. 2002;91:1245–1251. doi: 10.1002/jps.10122. [PubMed] [Cross Ref]
6. Hasçiçek C, Gönül N, Erk N. Mucoadhesive microspheres containing gentamicin sulfate for nasal administration: preparation and in vitro characterization. Farmaco. 2003;58:11–16. doi: 10.1016/S0014-827X(02)00004-6. [PubMed] [Cross Ref]
7. He P, Davis SS, Illum L. In vitro evaluation of the mucoadhesive properties of chitosan microspheres. Int J Pharm. 1998;166:75–88. doi: 10.1016/S0378-5173(98)00027-1. [Cross Ref]
8. Bruschi ML, Cardoso MLC, Lucchesi MB, Gremião MPD. Gelatin microparticles containing propolis obtained by spray-drying technique: preparation and characterization. Int J Pharm. 2003;264:45–55. doi: 10.1016/S0378-5173(03)00386-7. [PubMed] [Cross Ref]
9. Jones N. The nose and paranasal sinuses physiology and anatomy. Adv Drug Deliv Rev. 2001;51:5–19. doi: 10.1016/S0169-409X(01)00172-7. [PubMed] [Cross Ref]
10. Vidgren P, Vidgren M, Arppe J, Hakuli T. In vitro evaluation of spray-dried mucoadhesive microspheres for nasal administration. Drug Dev Ind Pharm. 1992;18:581–597. doi: 10.3109/03639049209043712. [Cross Ref]
11. Huang Y, Yeh M, Chiang C. Formulation factors in preparing BTM-chitosan microspheres by spray-drying method. Int J Pharm. 2002;242:239–242. doi: 10.1016/S0378-5173(02)00164-3. [PubMed] [Cross Ref]
12. Sacchetti C, Artusi M, Santi P, Colombo P. Caffeine microparticles for nasal administration obtained by spray-drying. Int J Pharm. 2002;242:335–339. doi: 10.1016/S0378-5173(02)00177-1. [PubMed] [Cross Ref]
13. Bhandari BR, Datta N, Howes T. Problems associated with spray-drying of sugar-rich foods. Dry Technol. 1997;15:671–684. doi: 10.1080/07373939708917253. [Cross Ref]
14. Miyazaki Y, Ogihara K, Yakou S, Nagai T, Takayama K. In vitro and in vivo evaluation of mucoadhesive microspheres consisting of dextran derivatives and cellulose acetate butyrate. Int J Pharm. 2003;258:21–29. doi: 10.1016/S0378-5173(03)00159-5. [PubMed] [Cross Ref]
15. Borchard G, Lueßen HL, de Boer AG, Verhoef JC, Lehr CM, Junginger HE. The potential of mucoadhesive polymers in enhancing intestinal peptide drug absorption. III. Effects of chitosan-glutamate and carbomer on epithelial tight junctions in vitro. J Control Release. 1996;39:131–138. doi: 10.1016/0168-3659(95)00146-8. [Cross Ref]
16. Bromberg L, Alakhov V. Effects of polyether-modified poly(acrylic acid) microgels on doxorubicin transport in human intestinal epithelial Caco-2 cell. J Control Release. 2003;88:11–22. doi: 10.1016/S0168-3659(02)00419-4. [PubMed] [Cross Ref]
17. Kissel T, Werner U. Nasal delivery of peptides: an in vitro cell culture model for the investigation of transport and metabolism in human nasal epithelium. J Control Release. 1998;53:195–203. doi: 10.1016/S0168-3659(97)00253-8. [PubMed] [Cross Ref]
18. Hoang VD, Uchenna AR, Mark J, Renaat K, Norbert V. Characterization of human nasal primary culture systems to investigate peptide metabolism. Int J Pharm. 2002;238:247–256. doi: 10.1016/S0378-5173(02)00077-7. [PubMed] [Cross Ref]
19. Kubo H, Hosoya K, Natsume H, Sugibayashi K, Morimoto Y. In vitro permeation of several model drugs across rabbit nasal mucosa. Int J Pharm. 1994;103:27–36. doi: 10.1016/0378-5173(94)90200-3. [Cross Ref]
20. Vyas SP, Talwar N, Karajgi JS, Jain NK. An erythrocyte based bioadhesive system for nasal delivery of propranolol. J Control Release. 1993;23:231–237. doi: 10.1016/0168-3659(93)90004-O. [Cross Ref]
21. Anderberg EK, Lindmark T, Artursson P. Sodium caprate elicits dilatations in human intestinal tight junctions and enhances drug absorption by the paracellular route. Pharm Res. 1993;10:857–864. doi: 10.1023/A:1018909210879. [PubMed] [Cross Ref]
22. Adhikari B, Howes T, Bhandari BR, Troung V. Effect of addition of maltodextrin on drying kinetics and stickiness of sugar and acid-rich foods during convective drying: experiments and modeling. J Food Eng. 2004;62:53–68. doi: 10.1016/S0260-8774(03)00171-7. [Cross Ref]
23. Ting TY, Gonda I, Gipps EM. Microspheres of polyvinyl alcohol for nasal delivery. I. Generation by spray-drying and spray-desolvation. Pharm Res. 1992;9:1330–1335. doi: 10.1023/A:1015869704171. [PubMed] [Cross Ref]
24. Chien YW, Su SK, Chang FS. Nasal Systemic Drug Delivery. New York, NY: Marcel Dekker; 1989. pp. 63–67.
25. Callens C, Ceulemans J, Ludwig A, Foreman P, Remon JP. Rheological study on mucoadhesivity of some nasal powder formulations. Eur J Pharm Biopharm. 2003;55:323–328. doi: 10.1016/S0939-6411(03)00024-9. [PubMed] [Cross Ref]
26. Agarwal V, Mishra B. Design, development, and biopharmaceutical properties of buccoadhesive compacts of pentazocine. Drug Dev Ind Pharm. 1999;25:701–709. doi: 10.1081/DDC-100102229. [PubMed] [Cross Ref]
27. Ritthidej GC, Phaechamud T, Koizumi T. Moist heat treatment on physicochemical change of chitosan salt films. Int J Pharm. 2002;232:11–22. doi: 10.1016/S0378-5173(01)00894-8. [PubMed] [Cross Ref]
28. Dodane V, Khan MA, Merwin JR. Effect of chitosan on epithelial permeability and structure. Int J Pharm. 1999;182:21–23. doi: 10.1016/S0378-5173(99)00030-7. [PubMed] [Cross Ref]
29. Artursson P, Lindmark T, Davis SS, Illum L. Effect of chitosan on the permeability of monolayers of intestinal epithelial cells (Caco-2) Pharm Res. 1994;11:1358–1361. doi: 10.1023/A:1018967116988. [PubMed] [Cross Ref]
30. Ryden L, Edman P. Effect of polymers and microspheres on the nasal absorption of insulin in rats. Int J Pharm. 1982;83:1–10. doi: 10.1016/0378-5173(82)90002-3. [Cross Ref]
31. Kotzé AF, Lueßen HL, de Leeuw BJ, de Boer ABG, Verhoef JC, Junginger HE. N-trimethyl chitosan chloride as a potential absorption enhancer across mucosal surface: in vitro evaluation in intestinal epithelial cells (Caco-2) Pharm Res. 1997;14:1197–1202. doi: 10.1023/A:1012106907708. [PubMed] [Cross Ref]
32. Schipper NGM, Vrum KM, Artursson P. Chitosan as absorption enhancers for poorly absorbable drugs. I. Influence of molecular weight and degree of acetylation on drug transport across human intestinal epithelial (Caco-2) cells. Pharm Res. 1996;13:1686–1691. doi: 10.1023/A:1016444808000. [PubMed] [Cross Ref]

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists