Abstract
In this study, the effect of Cremophor® RH 40 (CR 40) classic micelles and Soluplus® (SP) polymeric micelles were investigated on a novel granule-type drug-delivery system containing megestrolacetate (MGA). Using a risk assessment-based approach on the formulation via melt technology resulted in the formation of these granules, presented as the dosage, with proper particle size and flow characteristics. Due to the application of a eutectic carrier base composition, gentle process conditions were reached, retaining the crystalline structure of the carrier system and allowing for the proper distribution of MGA in the granules. The increased water solubility (0.111 mg/mL to 2.154 mg/mL), and the decreased nano particle size (102.27 nm) with uniform distribution (polydispersity index of 0.259) and colloid stability (zeta potential of −12.99 mV) resulted in SP polymeric micelles prevailing over CR 40 micelles in this gastric dissolution study, performed in biorelevant fasted and fed state drug-release media. Mathematical characterization and kinetic model fitting supported the fast drug-release mechanism of polymeric micelles over micelles. The value-added polymeric micelle-containing formulation developed can be successfully administered perorally and the enhanced drug release offers the possibility of greater drug absorption in the gastrointestinal tract.
Highlights
Surface-active excipients have been widely used in the pharmaceutical industry and in research and development processes due to their advantageous effects on drug applicability, solubility, and permeability enhancement [1]
The quality-by-design-driven risk assessment was performed to determine the risk factors related to the incorporation of the surfactants into the melt technology-produced
When assigning the relation severity, the physicochemical properties of each surfactant were taken into consideration along with prior knowledge and experiments about these materials and technology
Summary
Surface-active excipients have been widely used in the pharmaceutical industry and in research and development processes due to their advantageous effects on drug applicability, solubility, and permeability enhancement [1]. Classic surfactants are most commonly used to decrease the surface tension between oily and aqueous phases in emulsions or to stably suspend water-insoluble drugs. The main focus has become a specific group of surfactants, amphiphilic graft co-polymers, which are able to form nanoparticles in the form of polymeric micelles [2,3,4]. Cremophor® RH 40 (CR 40) is a hydrogenated castor oil used as a nonionic solubilizer and emulsifying agent to solubilize hydrophobic active substances in aqueous and alcoholic dosage forms. They form “ex tempore” small (10–30 nm) classic micelles besides physically coating the particles to keep them suspended or solubilized [5].
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