Disintegration Mediated Controlled Release Supersaturating Solid Dispersion Formulation of an Insoluble Drug: Design, Development, Optimization, and In Vitro Evaluation

Abstract

Abstract. The objective of this study was to develop a solid dispersion based controlled release system for drug substances that are poorly soluble in water. A wax-based disintegration mediated controlled release system was designed based on the fact that an amorphous drug can crystallize out from hydrophilic matrices. For this study, cilostazol (CIL) was selected as the model drug, as it exhibits poor aqueous solubility. An amorphous solid dispersion was prepared to assist the drug to attain a supersaturated state. Povidone was used as carrier for solid dispersion (spray drying technique), hydrogenated vegetable oil (HVO) as wax matrix former, and sodium carboxymethyl cellulose (NaCMC) as a disintegrant. The extreme vertices mixture design (EVMD) was applied to optimize the designed and developed composition. The optimized formulation provided a dissolution pattern which was equivalent to the predicted curve, ascertaining that the optimal formulation could be accomplished with EVMD. The release profile of CIL was described by the Higuchi's model better than zero-order, first-order, and Hixson-Crowell's model, which indicated that the supersaturation state of CIL dominated to allow drug release by diffusion rather than disintegration regulated release as is generally observed by Hixson-Crowell's model. The optimized composition was evaluated for disintegration, dissolution, XRD, and stability studies. It was found that the amorphous state as well as the dissolution profile of CIL was maintained under the accelerated conditions of 40°C/75% RH for 6 months.

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“…Medication discharge via transporter disintegration and debasement seems, by all accounts, to be a promising methodology for the all-encompassing arrival of SDS since this component doesn't need water take-up; along these lines, it is probably going to dispose of recrystallization issues 35 . While disintegration alludes to a deficiency of some piece of the polymer mass or the polymer spine, polymer debasement alludes to chain scissions in which chains are cut into oligomers and monomers 36 .…”

“…Lipids are a class of natural mixtures that are ordered as waxes, glycerides, greasy alcohols, and unsaturated fats. Waxes, which are esters of unsaturated fats and long-chain alcohols 69 , were utilized as the base for deterioration frameworks that forestalled recrystallization inside the tablets 35 . The presence of the wax limited water retention to the tablet surface, in this way, forestalling drug recrystallization.…”

“…The ideal definition followed Higuchi's delivery rate and steady. The delivery system was resolved to be dispersion from the lattice 35 .…”