[en] The controlled release of drugs for pulmonary, delivery is a research field which has been so far rather unexploited but is currently becoming increasingly attractive. The introduction part of this research article first details the potential advantages of solid lipid microparticles (SLMs) as drug carrier compared to liposomes and polymeric microspheres. The aim of this work is to use SLMs to impart a sustained release profile to a model drug, salbutamol acetonide (SA). SA was synthesized from salbutamol in order to increase the lipophilicity of this molecule and thereby to increase its incorporation efficiency into SLMs. SA-loaded SLMs were then produced by a hot emulsion technique followed by high-shear homogenisation and the manufacturing parameters were optimized using the experimental design methodology in order to reach a suitable particle size for pulmonary administration. Scanning electron micrographs showed that SLMs are spherical, have a smooth surface and that SA crystallises outside of the particles when the drug loading is higher than 20%. This was confirmed by X-ray diffraction. SA in vitro release study from SLMs showed that the release rate increased with SA loading but remained in every case lower than the dissolution rate of pure SA. (c) 2006 Elsevier B.V. All rights reserved.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Jaspart, Séverine ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique et magistrale
Bertholet, Pascal
Piel, Géraldine ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique et magistrale
Dogné, Jean-Michel ; Université de Liège - ULiège > Département de pharmacie > Département de pharmacie
Delattre, Luc ; Université de Liège - ULiège > Département de pharmacie > Département de pharmacie
Evrard, Brigitte ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique
Language :
English
Title :
Solid lipid microparticles as a sustained release system for pulmonary drug delivery
Publication date :
January 2007
Journal title :
European Journal of Pharmaceutics and Biopharmaceutics
Courrier H.M., Butz N., and Vandamme T.F. Pulmonary drug delivery systems: recent developments and prospects. Crit. Rev. Ther. Drug Carrier Syst. 19 (2002) 425-498
Groneberg D.A., Witt C., Wagner U., Chung K.F., and Fischer A. Fundamentals of pulmonary drug delivery. Respir. Med. 97 (2003) 382-387
Karathanasis E., Ayyagari A.L., Bhavane R., Bellamkonda R.V., and Annapragada A.V. Preparation of in vivo cleavable agglomerated liposomes suitable for modulated pulmonary drug delivery. J. Control. Release 103 (2005) 159-175
Labiris N.R., and Dolovich M.B. Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications. Br. J. Clin. Pharmacol. 56 (2003) 588-599
Hardy J.G., and Chadwick T.S. Sustained release drug delivery to the lungs: an option for the future. Clin. Pharmacokinet. 39 (2000) 1-4
Gupta P.K., and Adjei A.L. Modulated-release aerosol. In: Gupta P.K., and Adjei A.L. (Eds). Inhalation Delivery of Therapeutic Peptides and Proteins (2003), Marcel Dekker, New York 667-702
Finlay W.H., and Wong J.P. Regional lung deposition of nebulized liposome-encapsulated ciprofloxacin. Int. J. Pharm. 167 (1998) 121-127
Gonzalez-Rothi R.J., and Schreier H. Pulmonary delivery of liposome-encapsulated drugs in asthma therapy. Clin. Immunother. 4 (1995) 331-337
Schreier H., Gonzalez-Rothi R.J., and Stecenko A.A. Pulmonary delivery of liposomes. J. Control. Release 24 (1993) 209-223
Zeng X.M., Martin G.P., and Marriott C. The controlled delivery of drugs to the lung. Int. J. Pharm. 124 (1995) 149-164
Darwis Y., and Kellaway I.W. Nebulisation of rehydrated freeze-dried beclomethasone dipropionate liposomes. Int. J. Pharm. 215 (2001) 113-121
Kellaway I.W., and Farr S.J. Liposomes as drug delivery systems to the lung. Adv. Drug Deliv. Rev. 5 (1990) 149-161
Cook R.O., Pannu R.K., and Kellaway I.W. Novel sustained release microspheres for pulmonary drug delivery. J. Control. Release 104 (2005) 79-90
Taylor K.M.G., Taylor G., Kellaway I.W., and Stevens J. The stability of liposomes to nebulisation. Int. J. Pharm. 58 (1990) 57-61
El-Baseir M.M., and Kellaway I.W. Poly(l-lactic acid) microspheres for pulmonary drug delivery: release kinetics and aerosolization studies. Int. J. Pharm. 175 (1998) 135-145
Wichert B., and Rohdewald P. Low molecular weight PLA: a suitable polymer for pulmonary administered microparticles?. J. Microencapsul. 10 (1993) 195-207
Lai Y.L., Mehta R.C., Thacker A.A., Yoo S.D., McNamara P.J., and DeLuca P.P. Sustained bronchodilation with isoproterenol poly(glycolide-co-lactide) microspheres. Pharm. Res. 10 (1993) 119-125
Poyner E.A., Alpar H.O., Almeida A.J., Gamble M.D., and Brown M.R.W. A comparative study on the pulmonary delivery of tobramycin encapsulated into liposomes and PLA microspheres following intravenous and endotracheal delivery. J. Control. Release 35 (1995) 41-48
Edwards D.A., Hanes J., Caponetti G., Hrkach J., Ben Jebria A., Eskew M.L., Mintzes J., Deaver D., Lotan N., and Langer R. Large porous particles for pulmonary drug delivery. Science 276 (1997) 1868-1871
Armstrong D.J., Elliott P.N., Ford J.L., Gadsdon D., McCarthy G.P., Rostron C., and Worsley M.D. Poly-(d,l-lactic acid) microspheres incorporating histological dyes for intra-pulmonary histopathological investigations. J. Pharm. Pharmacol. 48 (1996) 258-262
Ben Jebria A., Chen D., Eskew M.L., Vanbever R., Langer R., and Edwards D.A. Large porous particles for sustained protection from carbachol-induced bronchoconstriction in guinea pigs. Pharm. Res. 16 (1999) 555-561
Cortesi R., Esposito E., Luca G., and Nastruzzi C. Production of lipospheres as carriers for bioactive compounds. Biomaterials 23 (2002) 2283-2294
Jaspart S., Piel G., Delattre L., and Evrard B. Solid lipid microparticles: formulation, preparation, characterisation, drug release and applications. Expert Opin. Drug Deliv. 2 (2005) 75-87
Trotta M., Cavalli R., Carlotti M.E., Battaglia L., and Debernardi F. Solid lipid micro-particles carrying insulin formed by solvent-in-water emulsion-diffusion technique. Int. J. Pharm. 288 (2005) 281-288
Sanna V., Kirschvink N., Gustin P., Gavini E., Roland I., Delattre L., and Evrard B. Preparation and in vivo toxicity study of solid lipid microparticles as carrier for pulmonary administration. AAPS PharmSciTech 5 (2003) Article 27
European Pharmacopoeia, fifth ed., 2005.
Caira M.R., Hunter R., Nassimbeni L.R., and Stevens A.T. Resolution of albuterol acetonide. Tetrahedron 10 (1999) 2175-2189
Bosquillon C., Lombry C., Preat V., and Vanbever R. Influence of formulation excipients and physical characteristics of inhalation dry powders on their aerosolization performance. J. Control. Release 70 (2000) 329-339
Passerini N., Perissuti B., Moneghini M., Voinovich D., Albertini B., Cavallari C., and Rodriguez L. Characterization of carbamazepine-Gelucire 50/13 microparticles prepared by a spray-congealing process using ultrasounds. J. Pharm. Sci. 91 (2002) 699-707
Passerini N., Perissuti B., Albertini B., Voinovich D., Moneghini M., and Rodriguez L. Controlled release of verapamil hydrochloride from waxy microparticles prepared by spray congealing. J. Control. Release 88 (2003) 263-275
Vippagunta S.R., Maul K.A., Tallavajhala S., and Grant D.J.W. Solid-state characterization of nifedipine solid dispersions. Int. J. Pharm. 236 (2002) 111-123
Venkateswarlu V., and Manjunath K. Preparation, characterization and in vitro release kinetics of clozapine solid lipid nanoparticles. J. Control. Release 95 (2004) 627-638
Jenning V., Thunemann A.F., and Gohla S.H. Characterisation of a novel solid lipid nanoparticle carrier system based on binary mixtures of liquid and solid lipids. Int. J. Pharm. 199 (2000) 167-177
