Design and optimization of diclofenac sodium controlled release solid dispersions by response surface methodology

Abstract

A 32 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 (Rel12) and drug release at the end of 3 hours (Rel3) 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, Rel12 and Rel3 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.

Evaluation of sodium diclofenac release using natural rubber latex as carrier

“…In contrast, sodium diclofenac powder exhibits a XRD pattern of a crystalline material with no amorphous component, with peaks appearing at 14.70, 20.48, 25.96, 26.40 and 27.20° at 2θ values 25 . The absence of crystallinity in the NaDic-NRL membrane indicates that NaDic is amorphous or molecularly disperse within the microparticles 25,26 . Amorphous NaDic has also been found by Li et al 27 , Manjunatha et al 28 , Lopes et al 29 and Maiti et al 30 showed barely irritant to rat skin.…”

Controlled Release Systems Containing Solid Dispersions: Strategies and Mechanisms

“…Other approaches based on those two basic methods have been suggested: gentle heating can be used to increase the solubility of components in the solvent method (126), or only the drug can be dissolved in the organic solvent, followed by adding the solutions to the melted carriers (127). Although the SD technique is commonly used to enhance the dissolution properties of poorly water-soluble drugs using hydrophilic polymeric carriers as dispersing agents (7), several studies on SDs have referred to "CR-SDs" using water-insoluble carriers such as EC (128), Eudragit (129), and Compritol (74) to produce sustained-release pharmaceutical forms of highly water-soluble drugs. By using SDs containing a polymer blend, such as HPC and EC, it is possible to precisely control the drug release rate of an extremely water-soluble drug, such as oxprenolol hydrochloride (130).…”

“…In another study, the granulation of highly soluble drugs such as dimenhydrinate was performed by the solvent evaporation technique, in which preheated ethanol was gradually added to a homogenous mixture of the drug and EC to dissolve the blend while continuously heating the mixture on a hot plate and slowly evaporating the solvent, followed by drying the mixture in an oven (128). Coprecipitates of different freely soluble drugs with Eudragit RS or RL were prepared by drying a mixed solution of polymer and drug in ethanol and/or methanol (129,131) through the solvent method. The melting method has been applied with waxy carriers such as Compritol 888 ATO (74) on the freely water-soluble drug sodium ferulate, in which the carrier is melted in a water bath at 75°C and the drug is added with continuous stirring to achieve a homogeneous dispersion.…”

Formulation and Optimization of Carbamazepine Microspheres by 2 Factor 2 Level Central Composite Design

“…Drug release at the end of 3 hours increased from 20.52 % to 32.66 % and from 37.52 % to 44.90 % at high and low levels of polymer ratio (Ethocel standard 45 premium: Eudragit RL 100) respectively as the drug loading increased. That indicates when the amount of Ethocel standard 45 premium was comparatively high it showed greater release retarding property due to its hydrophobic nature (Jain et al, 2010;Shivakumar et al, 2008).…”