Summary and Conclusion
Ramipril nanoemulsion formulations were successfully prepared by the spontaneous emulsification method (titration method). Sefsol 218 was selected as the oil phase for the development of the formulation on the basis of the solubility studies. The differences in the droplet size between the formulations selected from the phase diagram was not statistically significant, although the polydispersity was at a minimum for the formulation containing 20% oil, 27% Smix, and 53% vol/vol aqueous phase. The droplet size was found to be 34.5 nm. Therefore, nanoemulsion, a multipurpose technology, can be exploited in drug delivery for poorly soluble drugs. Nanoemulsions have a higher solubilization capacity than simple micellar solutions, and their thermodynamic stability offers advantages over unstable dispersions, such as emulsions and suspensions, because they can be manufactured with little energy input (heat or mixing) and have a long shelf life. This technical note explains the basis for calculation and construction of pseudoternary phase diagrams and, most important, explains selection of the formulations from the phase diagrams to avoid metastable formulations having minimum surfactant concentration in the least possible time.
Keywords: Ramipril, nanoemulsion, pseudoternary phase diagram, thermodynamic stability, solubility, droplet size
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References
- 1.Eccleston J. Microemulsions. In: Swarbrick J, Boylan JC, editors. Encyclopedia of Pharmaceutical Technology. New York, NY: Marcel Dekker; 1994. pp. 375–421. [Google Scholar]
- 2.Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Adv Drug Deliv Rev. 2000;45:89–121. doi: 10.1016/S0169-409X(00)00103-4. [DOI] [PubMed] [Google Scholar]
- 3.Rosano HL, Cavello JL, Lyons GB. Mechanism of formation of six microemulsion systems. In: Rosano HL, Clausse M, editors. Microemulsion Systems. New York, NY: Marcel Dekker; 1987. pp. 259–257. [Google Scholar]
- 4.Belal F, Al-Zaagi IA, Gadkariem MA, Abounassif MA. A stability-indicating LC method for the simultaneous determination of ramipril and hydrochloride in dosage forms. J Pharm Biomed Anal. 2001;24:335–342. doi: 10.1016/S0731-7085(00)00474-X. [DOI] [PubMed] [Google Scholar]
- 5.Gursoy RN, Benita S. Self-emulsifying drug delivery systems for improved oral delivery of lipophilic drugs. Biomed Pharmacother. 2004;58:173–182. doi: 10.1016/j.biopha.2004.02.001. [DOI] [PubMed] [Google Scholar]
- 6.Grove M, Pedersen GP, Nielsen JL, Mullertz A. Bioavailability of seocalcitol I: relating solubility in biorelevant media with oral bioavailability in rats—effect of medium and long chain triglycerides. J Pharm Sci. 2005;94:1830–1838. doi: 10.1002/jps.20403. [DOI] [PubMed] [Google Scholar]
- 7.Warisnoicharoen W, Lansley AB, Lawrence MJ. Light scattering investigations on dilute non-ionic oil-in-water microemulsions. AAPS PharmSci. 2000;2:12–12. doi: 10.1208/ps020212. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Constantinides PP, Lancaster CM, Marcello J, et al. Enhanced intestinal absorption of an RGD peptide from water-in-oil microemulsions of different composition and particle size. J Control Release. 1995;34:109–116. doi: 10.1016/0168-3659(94)00129-I. [DOI] [Google Scholar]
- 9.Ghosh PK, Murthy RSR. Microemulsions: a potential drug delivery system. Curr Drug Deliv. 2006;3:167–180. doi: 10.2174/156720106776359168. [DOI] [PubMed] [Google Scholar]
- 10.Pouton CW. Formulation of self-emulsifying drug delivery systems. Adv Drug Deliv Rev. 1997;25:47–58. doi: 10.1016/S0169-409X(96)00490-5. [DOI] [Google Scholar]