title: Design and optimization of diclofenac sodium controlled release solid dispersions by response surface methodology.
abstract: A 3(2) factorial design was employed to produce controlled release solid dispersions of diclofenac sodium in Eudragit RS and RL by coevaporation of their ethanol solution in a flash evaporator. The effect of critical formulation variables namely total polymer pay loads and levels of Eudragit RL on percent drug incorporation (% DI), drug release at the end of 12 hours (Rel(12)) and drug release at the end of 3 hours (Rel(3)) were analyzed using response surface methodology. The parameters were evaluated using the F test and mathematical models containing only the significant terms were generated for each parameter using multiple linear regression analysis and analysis of variance. Both the formulation variables studied exerted a significant influence (p < 0.05) on the drug release whereas the total polymer levels emerged as a lone factor significantly influencing the percent drug incorporation. Numerical optimization technique employing desirability approach was used to develop a new formulation by setting constraints on the dependent and independent variables. The experimental values of % DI, Rel(12) and Rel(3) for the optimized batch were found to be 95.22 +/- 1.13%, 74.52 +/- 3.16% and 29.37 +/- 1.26% respectively which were in close agreement with those predicted by the mathematical models. The Fourier transform infrared spectroscopy, Differential scanning calorimetry and Powder x-ray diffractometry confirmed that the drug was reduced to molecular or microcrystalline form in the hydrophobic polymeric matrices, which could be responsible for the controlled drug release from the solid dispersions. The drug release from the solid dispersions followed first order rate kinetics and was characterized by Higuchian diffusion model.
authors.affiliation: Department of Pharmaceutical Technology, K. L. E. S's College of Pharmacy, Rajajinagar 2 Block, Bangalore - 560 010, India.
authors.forename: H N
authors.initials: HN
authors.lastname: Shivakumar
authors.forename: B G
authors.initials: BG
authors.lastname: Desai
authors.forename: G
authors.initials: G
authors.lastname: Deshmukh
references.citation: Drug Dev Ind Pharm. 1995;21(3):315-330
references.pmid: 36600546
references.citation: J Pharm Sci. 1971 Sep;60(9):1281-302
references.pmid: 4935981
references.citation: Int J Pharm. 2005 Nov 4;304(1-2):102-14
references.pmid: 16150561
references.citation: Drugs. 1988 Mar;35(3):244-85
references.pmid: 3286213
references.citation: Eur J Pharm Biopharm. 1998 Jan;45(1):9-21
references.pmid: 9689531
references.citation: J Control Release. 1998 Oct 30;55(1):67-77
references.pmid: 9795017
references.citation: Chem Pharm Bull (Tokyo). 1985 Jan;33(1):388-91
references.pmid: 4006028
references.citation: AAPS PharmSciTech. 2002;3(2):E10
references.pmid: 12916947
references.citation: Eur J Pharm Biopharm. 2004 Jul;58(1):61-7
references.pmid: 15207538
references.citation: Pharm Acta Helv. 1986;61(3):69-88
references.pmid: 3520598
references.citation: Int J Pharm. 2001 May 7;218(1-2):27-42
references.pmid: 11337147
references.citation: J Pharm Sci. 1990 Sep;79(9):811-6
references.pmid: 2273466
references.citation: Int J Pharm. 2000 Feb 15;195(1-2):45-53
references.pmid: 10675682