Improvement of Dissolution Rate of Valsartan by Solid Dispersion System Using D(−) Mannitol

Abstract

Objective: To improve dissolution rate of valsartan from solid dispersion system of valsartan and D(−) mannitol using co-grinding approach. Methods:Valsartan solid dispersion with different ratio of D(−) mannitol (1:1; 1:3 and 1: 5) were prepared by co-grinding method. Solid state characterization of the solid dispersion system was evaluated in term of crystallographic properties (powder X-ray diffraction), thermal behavior (differential scanning calorimetry [DSC]) and morphology (scanning electron microscope). The profile of dissolution rate was examined using USP dissolution apparatus type I at a temperature of 37±0.5°C. Results:Based on thermal analysis DSC and powder X-ray diffraction analysis, valsartan was transformed from semicrystalline phase to amorphous state as indicated by the disappearance of its melting endothermic peaks and the characteristic diffraction peaks. The in vitro dissolution rate study revealed that all solid dispersion system showed significant increase in dissolution rate compared with the intact valsartan. Conclusion:Solid dispersion of valsartan with D(−) mannitol prepared by co-grinding technique has successfully improved the dissolution rate compared with intact valsartan.

Sugars and Polyols of Natural Origin as Carriers for Solubility and Dissolution Enhancement

“…This approach addresses issues, such as drug degradation, associated with the fusion technique-especially when there is a significant difference between the melting temperatures of the individual compounds-and toxicity risks linked to residual solvents in the case of solvent evaporation [95]. Valsartan-mannitol SDs were prepared using ball milling [96,97]. The outcomes of these studies indicated that the speed and time of milling are major factors in converting both components into an amorphous form, necessitating milling for over two hours.…”

Formulation and enhancement of dissolution rate of poorly aqueous soluble drug Aceclofenac by solid dispersion method: In vitro study

“…In the order of Mannitol > dextrose > HPMC > PVA, the rise in dissolution rate was noted. The release profile was higher with the formulation containing mannitol in the ratio 1:3 (F8) in both of the medium which might be due to generation of fine crystals of the drug when it comes in contact with dissolution medium resulting increase in wettability of the crystals, while release profile was lower with the formulation containing HPMC and PVA which might be due to the result of formation of viscous layer at the interface of drug and dissolution medium that hinders the diffusion of drug from the diffused layer to bulk layer (Rane et al, 2007;Zaini et al, 2017;Madgulkar et al, 2016). Similarly, the lower dissolution rate of PVA may be attributed to the weaker drug-polymer interaction in the PVA system that leads to the lower degree of amorphization and also due to its higher viscosity in solution, might hinder the transformation of the drug domain during dissolution (Chan et al, 2015).…”