In vitro and in vivo correlation for lipid-based formulations: Current status and future perspectives

Abstract

Lipid-based formulations (LBFs) have demonstrated a great potential in enhancing the oral absorption of poorly water-soluble drugs. However, construction of in vitro and in vivo correlations (IVIVCs) for LBFs is quite challenging, owing to a complex in vivo processing of these formulations. In this paper, we start with a brief introduction on the gastrointestinal digestion of lipid/LBFs and its relation to enhanced oral drug absorption; based on the concept of IVIVCs, the current status of in vitro models to establish IVIVCs for LBFs is reviewed, while future perspectives in this field are discussed. In vitro tests, which facilitate the understanding and prediction of the in vivo performance of solid dosage forms, frequently fail to mimic the in vivo processing of LBFs, leading to inconsistent results. In vitro digestion models, which more closely simulate gastrointestinal physiology, are a more promising option. Despite some successes in IVIVC modeling, the accuracy and consistency of these models are yet to be validated, particularly for human data. A reliable IVIVC model can not only reduce the risk, time, and cost of formulation development but can also contribute to the formulation design and optimization, thus promoting the clinical translation of LBFs.

Keywords: ANN, artificial neural network; AUC, area under the curve; Absorption; BCS, biopharmaceutics classification system; BE, bioequivalence; CETP, cholesterol ester transfer protein; Cmax, peak plasma concentration; DDS, drug delivery system; FDA, US Food and Drug Administration; GI, gastrointestinal; HLB, hydrophilic–lipophilic balance; IVIVC, in vitro and in vivo correlation; IVIVR, in vitro and in vivo relationship; In silico prediction; In vitro and in vivo correlations; LBF, lipid-based formulation; LCT, long-chain triglyceride; Lipid-based formulation; Lipolysis; MCT, medium-chain triglyceride; Model; Oral delivery; PBPK, physiologically based pharmacokinetic; PK, pharmacokinetic; Perspectives; SCT, short-chain triglyceride; SEDDS, self-emulsifying drug delivery system; SGF, simulated gastric fluid; SIF, simulated intestinal fluid; SLS, sodium lauryl sulfate; SMEDDS, self-microemulsifying drug delivery system; SNEDDS, self-nanoemulsifying drug delivery system; TIM, TNO gastrointestinal model; TNO, Netherlands Organization for Applied Scientific Research; Tmax, time to reach the peak plasma concentration.