Eutectic-based self-nanoemulsified drug delivery systems for solid oral dosage forms

Coenzyme Q₁₀ (CoQ₁₀) preparations that are commercially available suffer from poor compliance with the regulatory guidelines for quality, strength, and safety. Because of its poor solubility, CoQ₁₀ presents an additional challenge in the development of an oral formulation.; The objective of this dissertation was to develop a reversibly induced re-crystallized self-nanoemulsifying drug delivery system of CoQ₁₀. In this method, the eutectic interaction between CoQ₁₀ and essential oils allowed the formulation to melt at body temperature and disperse to form fine nanoemulsified droplets. Binary and pseudo ternary phase diagrams, FTIR analysis and droplet size measurements were used to characterize the eutectic interaction. The quality and ease of emulsion formation was further monitored by turbidimetry and dissolution studies. Formulation ingredients, Polyoxyl castor oil (surfactant), Medium-chain glycerides (co-surfactant), and Lemon oil were subsequently optimized for release rate by applying the Box-Behnken design.; As the eutectic-based formulation forms a paste with copolyvidone, it was possible to incorporate the optimized formulation into a tablet dosage form. Copolyvidone paste ground with maltodextrin produced granules with good flow and compression properties. Particle size and moisture content of the microcrystalline cellulose (MCC) added to the formulation were evaluated for their effect on compaction and dissolution of the solid formulation by applying Heckel analysis and profilometry. Solid formulation ingredients, copolyvidone, maltodextrin, and MCC, were then optimized using the Box Behnken design to obtain a level of the ingredients with desired dissolution rate and tensile strength.; Process variables, compression pressure, amount of silicon dioxide, and magnesium stearate mixing time were further evaluated for their effect on the controlled and constrained dissolution behavior of the tablet formulation. They were optimized using the face centered cubic design to obtain a tablet dosage form that delivers the lipid-formulation over eight hrs with zero order release kinetics. Optimized formulation was then subjected to an accelerated stability study. This study revealed the advantages of using eutectic-based lipid-based formulation in developing dosage forms for the delivery of poorly soluble compounds.