Current Status of Supersaturable Self-Emulsifying Drug Delivery Systems

Abstract

Self-emulsifying drug delivery systems (SEDDSs) are a vital strategy to enhance the bioavailability (BA) of formulations of poorly water-soluble compounds. However, these formulations have certain limitations, including in vivo drug precipitation, poor in vitro in vivo correlation due to a lack of predictive in vitro tests, issues in handling of liquid formulation, and physico-chemical instability of drug and/or vehicle components. To overcome these limitations, which restrict the potential usage of such systems, the supersaturable SEDDSs (su-SEDDSs) have gained attention based on the fact that the inclusion of precipitation inhibitors (PIs) within SEDDSs helps maintain drug supersaturation after dispersion and digestion in the gastrointestinal tract. This improves the BA of drugs and reduces the variability of exposure. In addition, the formulation of solid su-SEDDSs has helped to overcome disadvantages of liquid or capsule dosage form. This review article discusses, in detail, the current status of su-SEDDSs that overcome the limitations of conventional SEDDSs. It discusses the definition and range of su-SEDDSs, the principle mechanisms underlying precipitation inhibition and enhanced in vivo absorption, drug application cases, biorelevance in vitro digestion models, and the development of liquid su-SEDDSs to solid dosage forms. This review also describes the effects of various physiological factors and the potential interactions between PIs and lipid, lipase or lipid digested products on the in vivo performance of su-SEDDSs. In particular, several considerations relating to the properties of PIs are discussed from various perspectives.Pharmaceutics 2020, 12, 365 2 of 57 intraluminal supersaturation and the biorelevance of supersaturation assays will be addressed. Finally, we will make suggestions for the successful development of su-SEDDs.There are many review articles that give useful information about the nature and application of supersaturable drug delivery systems or conventional SEDDSs. However, these reviews cover only a limited range of su-SEDDSs. Therefore, this review, which includes the current status of technology focused only on su-SEDDSs, is a valuable addition to the previous review literature because no review article currently covers such a wide range of su-SEDDSs. Conventional Solubilized SEDDSsThere has been a steady increase in the number of new drug candidates (almost 40%) that are highly hydrophobic and poorly water-soluble. The oral bioavailability of poorly water-soluble drugs is hindered by low solubility and slow dissolution in the aqueous environment of the GIT. Thus, it is a great challenge for pharmaceutical scientists to overcome the inherent slow dissolution and poor oral absorption of hydrophobic drugs [1][2][3][4]. SEDDSs have emerged as a promising approach to improving the biopharmaceutical performance of hydrophobic drugs by enhancing their bioavailability [5,6].An SEDDS is a pre-concentrate composed of a drug, oils, surfactants, and sometimes co-solvents and/or co-surfactan...

Self-Nanoemulsifying Drug Delivery System of Genkwanin: A Novel Approach for Anti-Colitis-Associated Colorectal Cancer

“… 55 To date, many commercial SNEDDS drugs have been approved by FDA, such as kaletra ® (Ritonavir/Lopinavir), Aptivus ® (Tipranavir), Sandimmune ® (cyclosporine). 17 , 56 Given the advantages of the SNEDDS technology and its application in medicine, this study used it to increase the solubility and enhance the bioavailability of GKA.…”

Multivariate Design of 3D Printed Immediate-Release Tablets with Liquid Crystal-Forming Drug—Itraconazole

“…In all cases of 3D printed tablets, long-lasting supersaturation of the itraconazole was achieved. It is well-known that the persisting state of supersaturation may lead to bioavailability improvements, which is especially beneficial in terms of poorly soluble drugs such as itraconazole [77].…”

Self-Nano-Emulsifying Drug-Delivery Systems: From the Development to the Current Applications and Challenges in Oral Drug Delivery

“…Drug solubility in lipidic components is the key factor that determines the dose of a drug to be administered in a SNEDDS formulation [ 227 , 228 ]. As the oil content is reduced during the dispersion or digestion, the solubilizing capacity of SNEDDSs declines in vivo , leading to drug precipitation [ 229 ].…”

“…To overcome this drawback, supersaturated SNEDDSs (s-SNEDDSs) containing precipitation inhibitors have been suggested [ 228 ]. s-SNEDDSs are thermodynamically stable SNEDDSs containing a polymer (such as poly vinyl pyrrolidone (PVP) or hydroxypropylmethylcellulose) that should inhibit the nucleation process and subsequent drug precipitation, thus temporarily maintaining a supersaturated solution of the drug in the GI tract [ 233 , 234 , 235 ].…”

“…It provides information about functional groups and different chemical bonding between molecules. FTIR allows a study of the functional and structural modifications during the formulation and possible interactions between oils, surfactants, cosurfactants/cosolvents and molecules [ 54 , 228 ].…”