Multicomponent Inclusion Complex Of Poorly Soluble Drugs For Solubility And Bioavailability Enhancement

Abstract

This study investigates the characterization, solubility, dissolution, and pharmacokinetic properties of multicomponent inclusion complexes (MCICs) of Domperidone, Aceclofenac, and Lapatinib Ditosylate using cyclodextrins and auxiliary agents. Cyclodextrin derivatives, particularly Methyl-and#946;-cyclodextrin (M-and#946;-CD), demonstrated significant enhancements in the aqueous solubility and dissolution rates of these poorly soluble drugs. Ternary complexes incorporating auxiliary agents like Citric Acid, L-Arginine, and D-Mannitol were prepared using the kneading method, leading to up to a 42-fold increase in solubility for Domperidone and a notable improvement for Aceclofenac and Lapatinib Ditosylate. newlinePhase solubility studies revealed the formation of stable 1:1 inclusion complexes with enhanced stability constants, confirming effective drug-cyclodextrin interactions. FTIR, XRD, DSC, and 1H NMR analyses confirmed the successful complexation and the transformation of drugs from a crystalline to an amorphous state, contributing to increased solubility. Molecular modeling and docking studies further elucidated the binding interactions within the complexes, demonstrating the favorable thermodynamic stability of ternary complexes. newlineIn-vitro dissolution studies showed significantly enhanced drug release profiles for the ternary complexes compared to pure drugs and binary complexes. Domperidone and Aceclofenac ternary complexes achieved superior dissolution rates within 60 minutes, while Lapatinib Ditosylate demonstrated improved solubility in simulated gastrointestinal fluids. newlinePharmacokinetic studies in rats indicated increased bioavailability for the ternary complexes, with higher Cmax, AUC, and prolonged t½ compared to pure drugs. Stability assessments confirmed good stability under normal and accelerated conditions over three months, with minimal degradation. The findings suggest that multicomponent inclusion complexes are a promising strategy to enhance the solubility, dissolution, and bioavailability of poorly soluble drugs,