PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
 
AAPS PharmSciTech. 2003 March; 4(1): 71–79.
Published online 2003 February 2. doi:  10.1208/pt040110
PMCID: PMC2750306

Study of isopropyl myristate microemulsion systems containing cyclodextrins to improve the solubility of 2 model hydrophobic drugs

Abstract

The objectives of this project were to evaluate the effect of alkanols and cyclodextrins on the phase behavior of an isopropyl myristate microemulsion system and to examine the solubility of model drugs. Triangular phase diagrams were developed for the microemulsion systems using the water titration method, and the solubility values of progesterone and indomethacin were determined using a conventional shake-flask method. The water assimilation capacities were determined to evaluate the effective microemulsion formation in different systems. The alkanols showed higher microemulsion formation rates at higher concentrations. A correlation between the carbon numbers of the alkanol and water assimilation capacity in the microemulsions studied was observed; isobutanol and isopentanol produced the best results. The addition of cyclodextrins showed no effect or had a negative effect on the microemulsion formation based on the type of cyclodextrin used. Isopropyl myristate-based microemulsion systems alone could increase the solubility values of progesterone and indomethacin up to 3300-fold and 500-fold, respectively, compared to those in water. However, the addition of cyclodextrins to the microemulsion systems did not show a synergistic effect in increasing the solubility values of the model drugs. In conclusion, microemulsion systems improve the solubility of progesterone and indomethacin. But the two types of cyclodextrins studied affected isopropyl myristatebased microemulsion systems negatively and did not improve the solubilization of 2 model drugs.

Keywords: phase diagram, microemulsion, solubilization, cyclodextrin, surfactant, progesterone, indomethacin

Full Text

The Full Text of this article is available as a PDF (101K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Ritschel WA, Adolph S, Ritschel GB, Schroeder T. Improvement of peroral absorption of cyclosporin A by microemulsions. Methods Find Exp Clin Pharmacol. 1990;12:127–134. [PubMed]
2. Kim CK, Ryuu SA, Park KM, Lim SL, Hwang SJ. Preparation and physiochemical characterization of phase inverted water/oil microemulsion containing cyclosporin. A Int J Pharm. 1996;147:131–134. doi: 10.1016/S0378-5173(96)04791-6. [Cross Ref]
3. Linn E.E. Microemulsion for intradermal delivery of cetyl alcohol and octyl dimethyl PABA. Drug Dev Ind Pharm. 1990;16:899–920. doi: 10.3109/03639049009114917. [Cross Ref]
4. Garcia-Celma MJ, Azemar N, Pes MA, Solans C. Solubilization of antifungal drugs in water/POE (20) sorbitan monooleate/oil systems. Int J Pharm. 1994;105:77–81. doi: 10.1016/0378-5173(94)90238-0. [Cross Ref]
5. Thevenin MA, Grossiord JL, Poelman MC. Sucrose esters/cosurfactant microemulsion systems for transdermal delivery: assessment of bicontinuous structures. Int J Pharm. 1996;137:177–186. doi: 10.1016/0378-5173(96)04518-8. [Cross Ref]
6. Corswant CV, Thoren P, Engstrom S. Triglyceride-based microemulsion for intravenous administration of sparingly soluble substances. J Pharm Sci. 1998;87:200–208. doi: 10.1021/js970258w. [PubMed] [Cross Ref]
7. D’ Cruz OJ, Yiv SH, Uckun FM. GM-144, a novel lipophilic vaginal contraceptive gel-microemulsion. AAPS Pharm Sci Tech. 2001;2(2):5–5. [PMC free article] [PubMed]
8. Rajewski RA, Stella VJ. Pharmaceutical applications of cyclodextrins, II: in vivo drug delivery. J Pharm Sci. 1996;85:1142–1169. doi: 10.1021/js960075u. [PubMed] [Cross Ref]
9. Piel G, Evrad B, Fillet M, Labres G, Dellatre L. Development of a non-surfactant parenteral formulation of miconazole by use of cyclodextrins. Int J Pharm. 1998;169:15–22. doi: 10.1016/S0378-5173(98)00103-3. [Cross Ref]
10. Loftsson T, Brewster ME. Pharmaceutical application of cyclodextrins, I: drug solubilization and stabilization. J Pharm Sci. 1996;85:1017–1025. doi: 10.1021/js950534b. [PubMed] [Cross Ref]
11. Stella VJ, Rajewski RA. Cyclodextrins: their future in drug formulation and delivery. Pharm Res. 1997;14:556–567. doi: 10.1023/A:1012136608249. [PubMed] [Cross Ref]
12. Szente L, Szejtli J. Highly soluble cyclodextrin derivatives: chemistry, properties and trends in development. Adv Drug Deliv Rev. 1999;36:17–28. doi: 10.1016/S0169-409X(98)00092-1. [PubMed] [Cross Ref]
13. Dalmora ME, Oliveria AG. Inclusion complex of piroxicam with β-cyclodextrin and incorporation in hexadecyltrimethylammonium bromide based microemulsion. Int J Pharm. 1999;184:157–164. doi: 10.1016/S0378-5173(99)00099-X. [PubMed] [Cross Ref]
14. Dalmora ME, Dalmora SL, Oliveria AG. Inclusion complex with piroxicam with β-cyclodextrin and incorporation in cationic microemulsion: in vitro drug release and in vivo topical anti-inflammatory effect. Int J Pharm. 2001;222:45–55. doi: 10.1016/S0378-5173(01)00692-5. [PubMed] [Cross Ref]
15. Attwood D, Mallon C, Kristis G, Taylor CJ. A study of factors influencing the droplet size in nonionic oil-in-water microemulsions. Int J Pharm. 1992;88:417–422. doi: 10.1016/0378-5173(92)90341-X. [Cross Ref]
16. Alany RG, Rades T, Agatonovic-Kustrin S, Davies NM, Tucker IG. Effects of alcohols and diols on phase behavior of quaternary systems. Int J Pharm. 2000;191:141–145. doi: 10.1016/S0378-5173(99)00408-1. [PubMed] [Cross Ref]
17. Pitha J, Milecki J, Fales H, Pannell L, Uekema K. Hydroxypropyl-β-cyclodextrin: preparation and characterization; effects on solubility of drugs. Int J Pharm. 1986;29:73–82. doi: 10.1016/0378-5173(86)90201-2. [Cross Ref]
18. Nandi I, Bateson M, Bari M, Joshi H. Synergistic effect of PEG-400 and cyclodextrin to enhance solubility of progesterone. AAPS PharmSciTech. 2003;4(1) article 1. [PMC free article] [PubMed]
19. Johnson KA, Shah DO. Effect of oil chain length and electrolytes on water solubilization in alcohol-free pharmaceutical microemulsions. J Colloid Interface Sci. 1985;107(1):269–271. doi: 10.1016/0021-9797(85)90172-9. [Cross Ref]

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