Search tips
Search criteria 


Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
AAPS PharmSciTech. 2002 February; 3(4): 52.
Published online 2002 November 7. doi:  10.1208/pt030432
PMCID: PMC2751340

The effect of cosolvents on the formulation of nanoparticles from low-molecular-weight poly(I)lactide


The aim of this study was to formulate nanoparticles from poly(I)lactide by a modified nanoprecipitation method. The main focus was to study the effect of cosolvent selection on the shape, size, formation efficiency, degree of crystallinity, x-ray diffraction (XRD) reflection pattern, and zeta potential value of the particles. Low-molecular-weight (2000 g/mol) poly(I)lactide was used as a polymer, and sodium cromoglycate was used as a drug. Acetone, ethanol, and methanol were selected as cosolvents. Optimal nanoparticles were achieved with ethanol as a cosolvent, and the formation efficiency of the particles was also higher with ethanol as compared with acetone or methanol. The particles formulated by ethanol and acetone appeared round and smooth, while with methanol they were slightly angular. When the volume of the inner phase was decreased during the nanoprecipitation process, the mean particle size was also decreased with all the solvents, but the particles were more prone to aggregate. The XRD reflection pattern and the degree of crystallinity were more dependent were more prone to aggregate. The XRD reflection pattern and the degree of crystallinity were more dependent on the amount of the solvents in the inner phase than on the properties of the individual cosolvents. The zeta potential values of all the particle batches were slightly negative, which partially explains the increased tendency toward particle aggregation.

Keywords: nanoparticles, nanoprecipitation, poly(I)lactide, sodium cromoglycate, XRD, zeta potential

Full Text

The Full Text of this article is available as a PDF (445K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Masinde LE, Hickey AJ. Aerosolized aqueous suspensions of poly(l-lactic acid) microspheres. Int J Pharm. 1993;100:123–131. doi: 10.1016/0378-5173(93)90083-R. [Cross Ref]
2. Zhang Q, Shen Z, Nagai T. Prolonged hypoglycemic effect of insulin-loaded polybutylcyanoacrylate nanoparticles after pulmonary administration to normal rats. Int J Pharm. 2001;218:75–80. doi: 10.1016/S0378-5173(01)00614-7. [PubMed] [Cross Ref]
3. Kostanski JW, DeLuca PP. A novel in vitro release technique for peptide-containing biodegradable microspheres. AAPS PharmSciTech. 2000;1(1):article 4. [PMC free article] [PubMed]
4. Martin TM, Bandi N, Shulz R, Roberts CB, Kompella UB. Preparation of budesonide and budesonide-PLA microparticles using super-critical fluid precipitation technology. AAPS PharmSciTech. 2002;3(3):article 18. [PMC free article] [PubMed]
5. Perugini P, Genta I, Conti B, Modena T, Pavanetto F. Long-term release of clodronate from biodegradable microspheres. AAPS PharmSciTech. 2001;2(3):article 10. [PMC free article] [PubMed]
6. Jonnalagadda S, Robinson DH. A bioresorbable, polylactide reservoir for diffusional and osmotically controlled drug delivery. 00AAPS PharmSciTech. 2000;1(4):article 29. [PMC free article] [PubMed]
7. Lescure F, Seguin C, Breton P, Roy D, Couvreur P. Preparation and characterization of novel poly(methylidene malonate 2.1.2)-made nanoparticles. Pharm Res. 1994;11:1270–1277. doi: 10.1023/A:1018986226557. [PubMed] [Cross Ref]
8. Fessi H, Puisieux F, Devissaguet JP, Ammoury N, Benita S. Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm. 1989;55:R1–R4. doi: 10.1016/0378-5173(89)90281-0. [Cross Ref]
9. Ammoury N, Fessi H, Devissaguet JP, Dubrasquet M, Benita S. Jejunal absorption, pharmacological activity, and pharmacokinetic evaluation of indomethacin-loaded poly(d,l-lactide) and poly(isobutylcyanoacrylate) nanocapsules in rats. Pharm Res. 1991;8:101–105. doi: 10.1023/A:1015846810474. [PubMed] [Cross Ref]
10. Verger ML-L, Fluckiger L, Kim Y-I, Hoffman M, Maincent P. Preparation and characterization of nanoparticles containing an antihypertensive agent. Eur J Pharm Biopharm. 1998;46:137–143. doi: 10.1016/S0939-6411(98)00015-0. [PubMed] [Cross Ref]
11. Niwa T, Takeuchi H, Hino T, Kunou N, Kawashima Y. Preparations of biodegradable nanospheres of water-soluble and insoluble drugs with d,l-lactide/glycolide copolymer by a novel spontaneous emulsification solvent diffusion method, and the drug release behavior. J Control Release. 1993;25:89–98. doi: 10.1016/0168-3659(93)90097-O. [Cross Ref]
12. Wichert B, Rohdewald P. A new method for the preparation of drug containing polylactic acid microparticles without using organic solvents. J Control Release. 1990;14:269–283. doi: 10.1016/0168-3659(90)90167-R. [Cross Ref]
13. Wichert B, Rohdewald P. Low molecular weight PLA: a suitable polymer for pulmonary administered microparticles? J Microencapsul. 1993;10:195–207. doi: 10.3109/02652049309104385. [PubMed] [Cross Ref]
14. Thioune O, Fessi H, Devissaguet JP, Puisieux F. Preparation of pseudolatex by nanoprecipitation: influence of the solvent nature on intrinsic viscosity and interaction constant. Int J Pharm. 1997;146:233–238. doi: 10.1016/S0378-5173(96)04830-2. [Cross Ref]
15. Jeffery H, Davis SS, OHagan DT. The preparation and characterisation of poly(lactide-co-glycolide) microparticles. I: Oil-in-water emulsion solvent evaporation. Int J Pharm. 1991;77:169–175. doi: 10.1016/0378-5173(91)90314-E. [Cross Ref]
16. Wehrle P, Magenheim B, Benita S. The influence of process parameters on the PLA nanoparticle size distribution, evaluated by means of factorial design. Eur J Pharm Biopharm. 1995;41:19–26.
17. Molpeceres J, Guzman M, Aberturas MR, Chacon M, Berges L. Application of central composite designs to the preparation of polycaprolactone nanoparticles by solvent displacement. J Pharm Sci. 1996;85:206–213. doi: 10.1021/js950164r. [PubMed] [Cross Ref]
18. Murakami H, Kobayashi M, Takeuchi H, Kawashima Y. Preparation of poly(dl-lactide-co-glycolide) nanoparticles by modified spontaneous emulsification solvent diffusion method. Int J Pharm. 1999;187:143–152. doi: 10.1016/S0378-5173(99)00187-8. [PubMed] [Cross Ref]
19. Herrmann J, Bodmeier R. Biodegradable, somatostatin acetate containing microspheres prepared by various aqueous and non-aqueous solvent evaporation methods. Eur J Pharm Biopharm. 1998;45:75–82. doi: 10.1016/S0939-6411(97)00125-2. [PubMed] [Cross Ref]
20. Devissaguet J-P, Fessi H, Puisieux F. Process for the preparation of dispersible colloidal systems of a substance in the form of nanocapsules. US Patent 5 049 322. September 17, 1991.
21. Mehta RC, Thanoo BC, DeLuca PP. Peptide containing microspheres from low molecular weight and hydrophilic poly(d,l-lactide-coglycolide) J Control Release. 1996;41:249–257. doi: 10.1016/0168-3659(96)01332-6. [Cross Ref]
22. Ueda M, Kreuter J. Optimization of the preparation of loperamide-loaded poly(L-lactide) nanoparticles by high pressure emulsification-solvent evaporation. J Microencapsul. 1997;14:593–605. doi: 10.3109/02652049709006812. [PubMed] [Cross Ref]
23. Murakami H, Kobayashi M, Takeuchi H, Kawashima Y. Further application of a modified spontaneous emulsification solvent diffusion method to various types of PLGA and PLA polymers for preparation of nanoparticles. Powder Technol. 2000;107:137–143. doi: 10.1016/S0032-5910(99)00182-5. [Cross Ref]
24. Cox JSG, Woodard GD, McCrone WC. Solid-state chemistry of cromolyn sodium (disodium cromoglycate) J Pharm Sci. 1971;60:1458–1465. doi: 10.1002/jps.2600601003. [PubMed] [Cross Ref]
25. Chen LR, Young VG, Lechuga-Ballesteros D, Grant DJW. Solid-state behavior of cromolyn sodium hydrates. J Pharm Sci. 1999;88:1191–1200. doi: 10.1021/js9900710. [PubMed] [Cross Ref]
26. Müller RH, Kayser CJO. Nanosuspensions as particulate drug formulations in therapy: rationale for development and what we can expect for the future. Adv Drug Deliv Rev. 2001;47:3–19. doi: 10.1016/S0169-409X(00)00118-6. [PubMed] [Cross Ref]
27. Konno T, Kurita K, Iwasaki Y, Nakabayashi N, Ishihara K. Preparation of nanoparticles composed with bioinspired 2-methacryloyloxyethyl phosphorylcholine polymer. Biomaterials. 2001;22:1883–1889. doi: 10.1016/S0142-9612(00)00373-2. [PubMed] [Cross Ref]

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