pH-Independent Dissolution and Enhanced Oral Bioavailability of Aripiprazole-Loaded Solid Self-microemulsifying Drug Delivery System.

The present study pursued the systematic development of a stable solid self-emulsifying drug delivery system (SMEDDS) of an atypical antipsychotic drug, aripiprazole (APZ), which exhibits poor aqueous solubility and undergoes extensive p-glycoprotein efflux and hepatic metabolism. Liquid SMEDDS excipients were selected on the basis of solubility studies, and the optimum ratio of surfactant/co-surfactant was determined using pseudo-ternary phase diagrams. The prepared formulations were subjected to in vitro characterization studies to facilitate the selection of optimum liquid SMEDD formulation containing 30% Labrafil® M 1944 CS, 46.7% Cremophor® EL and 23.3% PEG 400 which were further subjected to solidification using maltodextrin as a hydrophilic carrier. The optimized solid SMEDDS was extensively evaluated for stability under accelerated conditions, dissolution at various pH and pharmacokinetic profile. Solid-state attributes of the optimized solid SMEDDS indicated a marked reduction in crystallinity of APZ and uniform adsorption of liquid SMEDDS. Stability study of the solid SMEDDS demonstrated that the developed formulation retained its stability during the accelerated storage conditions. Both the optimized liquid and solid SMEDDS exhibited enhanced dissolution rate which was furthermore independent of the pH of the dissolution medium. Oral bioavailability studies in Sprague-Dawley rats confirmed quicker and greater extent of absorption with solid SMEDDS as evident from the significant reduction in Tmax in case of solid SMEDDS (0.83 ± 0.12 h) as compared with commercial tablet (3.33 ± 0.94 h). The results of the present investigation indicated the development of a stable solid SMEDDS formulation of APZ with enhanced dissolution and absorption attributes.

Polymeric Precipitation Inhibitor Assisted Supersaturable SMEDDS of Efavirenz Based on Experimental Observations and Molecular Mechanics.

BACKGROUND: Supersaturable SMEDDS, a versatile dosage form, was investigated for improving the biopharmaceutical attributes and eradicating the food effect of poorly water soluble drug efavirenz. OBJECTIVE: The present research pursues the development of efavirenz loaded Supersaturable Self- Microemulsifying Drug Delivery System (SS SMEDDS) for improving biopharmaceutical performance. METHODS: Preformulation studies were carried out to determine the optimized range of lipid excipients to develop stable supersaturated SMEDDS (ST SMEDDS). The SS SMEDD formulation was prepared by adding hydroxypropyl methylcellulose as a polymeric precipitation inhibitor. The developed SS SMEDDS were evaluated for supersaturation behavior by performing in vitro supersaturation studies and molecular simulations by in silico docking. Dissolution was performed in biorelevant media to simulate fed/fasted conditions in gastrointestinal regions. Absorption behavior was determined through in vivo pharmacokinetics approach. RESULTS: The optimized ST SMEDDS formulation containing Maisine® CC, Tween 80 and Transcutol-P exhibited thermodynamic stability with quick rate of emulsification. The optimized SS SMEDDS containing suitable polymeric precipitation inhibitor exhibited enhanced efavirenz concentration in in vitro supersaturation test. The theoretical simulations by molecular docking revealed strong intermolecular interactions with a docking score of -3.004 KJ/mol. The dissolution performance of marketed product in biorelevant dissolution media inferred the existence of food effect in the dissolution of efavirenz. However, in SS SMEDDS, no significant differences in drug release behavior under different fasted/fed conditions signify that the food effect was neutralized. In vivo pharmacokinetics revealed a significant increase in the absorption profile of efavirenz from SS SMEDDS than that of ST SMEDDS and marketed product. CONCLUSION: The designed delivery system indicated promising results in developing an effectual EFV formulation for HIV treatment.

Applications of Molecular Dynamic Simulations in Lipid-Based Drug Delivery System.

Lipid-based drug delivery systems (LBDDSs) have widely been investigated as potential carriers for targeting water-insoluble molecules. However, the structural integrity, drug localization, and droplet stability are critical factors that need to be considered. Molecular dynamics simulations (MDS) is an in silico technique that provides a useful approach for molecularly simulating the system and provide critical appraisal of various features of LBDDS. MDS is a hybrid technique that provides the key formulations properties before the experimental setup that provides information on stable attributes of a lipid-based formulation. In this review, we have summarized critical information of molecular dynamics, simulation procedure, software utilized, and applications in lipid-based drug delivery field.