PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
 
AAPS PharmSciTech. 2004 December; 5(4): 114–121.
Published online 2004 April 26. doi:  10.1208/pt050466
PMCID: PMC2750491

Response surface methodology for optimization and characterization of limonene-based coenzyme Q10 self-nanoemulsified capsule dosage form

Abstract

The aim of this study was to systematically obtain a model of factors that would yield an optimized self-nanoemulsified capsule dosage form (SNCDF) of a highly lipophilic model compound, Coenzyme Q10 (CoQ). Independent variables such as amount of R-(+)-limonene (X1), surfactant (X2), and cosurfactant (X3), were optimized using a 3-factor, 3-level Box-Behnken statistical design. The dependent variables selected were cumulative percentage of drug released after 5 minutes (Y1) with constraints on drug release in 15 minutes (Y2), turbidity (Y3), particle size (Y4), and zeta potential (Y5). A mathematical relationship obtained,Y1=78.503+6.058X1 +13.738X2+5.986X3−25.831X12+9.12X1X2−26.03X1X3−38.67X22 +11.02X2X3−15.55X33 (r2=0.97), explained the main and quadratic effects, and the interaction of factors that affected the drug release. Response surface methodology (RSM) predicted the levels of factorsX1,X2, andX3 (0.0344, 0.216, and 0.240, respectively), for a maximized response ofY1 with constraints of >90% release onY2. The observed and predicted values ofY1 were in close agreement. In conclusion, the Box-Behnken experimental design allowed us to obtain SNCDF with rapid (>90%) drug release within 5 minutes with desirable properties of low turbidity and particle size.

Keywords: response surface methodology, Box-Behnken design, coenzyme Q10, R-limonene, statistical modeling

Full Text

The Full Text of this article is available as a PDF (231K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Nazzal S, Khan MA. Response surface methodology for the optimization of ubiquinone self-nanoemulsified drug delivery system. AAPS PharmSciTech. 2002;3(1):E3–E3. doi: 10.1208/pt030103. [PMC free article] [PubMed] [Cross Ref]
2. Nazzal S, Zaghloul AA, Reddy IK, Khan MA. Analysis of ubidecarenone (CoQ10) aqueous samples using reversed phase liquid chromatography. Pharmazie. 2001;56:394–396. [PubMed]
3. Pouton CW. Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and self-microemulsifying drug delivery systems. Eur J Pharm Sci. 2000;11(suppl 2):S93–S98. doi: 10.1016/S0928-0987(00)00167-6. [PubMed] [Cross Ref]
4. Charman SA, Charman WN, Rogge MC, Wilson TD, Dutko FJ, Pouton CW. Self-emulsifying drug delivery systems: formulation and biopharmaceutic evaluation of an investigational lipophilic compound. Pharm Res. 1992;9:87–93. doi: 10.1023/A:1018987928936. [PubMed] [Cross Ref]
5. Li S, Lin S, Chien YW, Daggy BP, Mirchandani HL. Statistical optimization of gastric floating system for oral controlled delivery of calcium. AAPS PharmSciTech. 2001;2(1):E1–E1. doi: 10.1208/pt020101. [PMC free article] [PubMed] [Cross Ref]
6. Chopra RK, Goldman R, Sinatra ST, Bhagavan HN. Relative bioavailability of coenzyme Q10 formulations in human subjects. Int J Vitam Nutr Res. 1998;68:109–113. [PubMed]
7. Sastry SV, Khan MA. Aqueous based polymeric dispersion: Plackett-Burman design for screening of formulation variables of atenolol gastrointestinal therapeutic system. Pharm Acta Helv. 1998;73:105–112. doi: 10.1016/S0031-6865(97)00052-6. [PubMed] [Cross Ref]
8. Korakianiti ES, Rekkas DM, Dallas PP, Choulis NH. Optimization of the pelletization process in a fluid-bed rotor granulator using experimental design. AAPS PharmSciTech. 2000;1(4):E35–E35. doi: 10.1208/pt010435. [PMC free article] [PubMed] [Cross Ref]
9. Abu-Izza K, Garcia-Contreras L, Lu DR. Preparation and evaluation of zidovudine-loaded sustained-release microspheres. 2. Optimization of multiple response variables. J Pharm Sci. 2004;85:572–576. doi: 10.1021/js960021k. [PubMed] [Cross Ref]
10. Hamed E, Sakr A. Application of multiple response optimization technique to extended release formulations design. J Control Release. 2001;73:329–338. doi: 10.1016/S0168-3659(01)00356-X. [PubMed] [Cross Ref]
11. Boza A, Cruz Y, Jordan G, Jauregui-Haza U, Aleman A, Caraballo I. Statistical optimization of a sustained-release matrix tablet of lobenzarit disodium. Drug Dev Ind Pharm. 2000;26:1303–1307. doi: 10.1081/DDC-100102313. [PubMed] [Cross Ref]
12. Box GEP, Wilson KB. On the experimental attainment of optimum multifactorial conditions. Royal Statistics Society. 1951;13:1–12.
13. Singh SK, Dodge J, Durrani MJ, Khan MA. Optimization and characterization of controlled release pellets coated with experimental latex: I. Anionic drug. Int J Pharm. 1995;125:243–255. doi: 10.1016/0378-5173(95)00135-6. [Cross Ref]
14. Sanchez-Lafuente C, Furlanetto S, Fernandez-Arevalo M, et al. Didanosine extended-release matrix tablets: optimization of formulation variables using statistical experimental design. Int J Pharm. 2002;237:107–118. doi: 10.1016/S0378-5173(02)00028-5. [PubMed] [Cross Ref]
15. Ragonese R, Macka M, Hughes J, Petocz P. The use of the Box-Behnken experimental design in the optimisation and robustness testing of a capillary electrophoresis method for the analysis of ethambutol hydrochloride in a pharmaceutical formulation. J Pharm Biomed Anal. 2002;27:995–1007. doi: 10.1016/S0731-7085(01)00659-8. [PubMed] [Cross Ref]
16. Box GEP, Behnken DW. Some new three level designs for the study of quantitative variables. Technometrics. 1960;2:455–475. doi: 10.2307/1266454. [Cross Ref]
17. Craig DQM, Barker SA, Banning D, Booth SW. An investigation into the mechanism of self-emulsification using particle size analysis and low frequency dielectric spectroscopy. Int J Pharm. 1995;114:103–110. doi: 10.1016/0378-5173(94)00222-Q. [Cross Ref]
18. Khan MA, Dib J, Reddy IK. Statistical optimization of Ketoprofen-Eudragit S100 coprecipitates to obtain controlled-release tablets. Drug Dev Ind Pharm. 2004;22:135–141. doi: 10.3109/03639049609041983. [Cross Ref]
19. Box GEP, Hunter WG, Hunter JS. Statistics for Experimenters: An Introduction to Design, Data Analysis, and Model Building. New York, NY: John Wiley & Sons; 1976.
20. Leiberman HA, Reiger MM, Banker GS. Pharmaceutical Dosage Forms: Disperse Systems. New York, NY: Mercel Dekker; 1989.

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