FaSSIF

FaSSIF fasted-state simulated artificial intestinal fluid... 

A composition for the upper small intestine in the fasted state (FaSSIF) is presented, as well as the buffer (FaSSIF-biank) solution which forms the basis of this medium. In order to precisely assess the effect of bile salts on solubility and... 

It should be noted that this procedure needs to be carried out on a case-by-case basis—there is no indication that the relative solubilization capacity (ability of bile components or surfactants to enhance solubility/dissolution of a drug) is consistent from drug to drug. Therefore, use of a standard medium containing a synthetic surfactant to correspond to either FaSSIF or FeSSIF results is not possible. 

The transfer model (15) can be used to answer the question of whether the drug is successfully released in the stomach, only to precipitate when it moves into the higher pH environment of the small intestine. As depicted in Figure 8, the pure drug (or formulation) is added to a gastric simulating medium at time zero, after which it is allowed to dissolve and simultaneously transferred into a second vessel containing FaSSIF or other suitable biorelevant medium. 

Figure 9 Typical results observed during the transfer of a poorly soluble, weak base from an acidic medium to FaSSIF.

Upper ileum FaSSIF (7.2)a halved (bile components) FaSSIF (7.2)a... 

In an attempt to increase the biorelevance of the Ussing chambers technique even further, the use of simulated intestinal fluids (FaSSIF and FeSSIF) as transport media was recently evaluated [105], However, the potential difference collapsed to zero after 120 min when exposed to FaSSIF solution and permeability for mannitol was increased twofold. Electron micrographs revealed erosion of the villi tips and substantial denudation of the microvilli after exposure of the ileal tissue to FaSSIF and FeSSIF [105],... 

Table 19.1 Composition of various buffer systems possibly eligible for combined dissolution and permeation testing. Concentrations may vary from reference to reference. Composition of FaSSIF and FeSSIF is shown as reported by Galia et al. [3] in the meantime, several publications denoted a change from potassium to sodium as the main cation [91] or others changes. Abbreviations are given in the text. 

The applicability of PBPK models can be described in the context of the BDDCS classification [24]. PBPK models are very predictive for class 1 and class 2 compounds. However for poorly soluble compounds, the use of aqueous solubility is shown to be inadequate for reliable prediction of oral absorption in physiologically based models [7]. In such cases, it is recommended to use solubility measured in simulated intestinal fluids (FeSSIF, FaSSIF). Such data proved to be very relevant to simulate the oral absorption of BCS 2 (low solubility, high permeability) compounds [25]. 

Ingredient FaSSGF Stomach (Fasted State) FaSSIF Small Intestine (Fasted State) FeSSIF Small Intestine (Fed State)... 

In order to establish an appropriate acceptance criterion, the additional dissolution studies with biorelevant dissolution media FaSSIF in Table 6.1 were conducted, and the results are shown in Figure 6.5. Figure 6.5 indicates that the dissolution rate has been uniformly increased, and all three lots pass the acceptance criterion of 80% in 30 min. On the basis of these biorelevant dissolution results along with the bioequivalence study data, the acceptance criterion was reduced to 70% in 30 min. 

FIGURE 6.5 Dissolution of three lots of drug B tablet in pH 6.8 FaSSIF. 

It is important to characterize the physicochemical properties of the suspensions well, so that the PK data can be interpreted appropriately. Typical characterization of the drug substance includes purity, residual solvents, aqueous solubility pro Lie (pH 2, FaSSIF), crystallinity (XRPD/DSC), particle size, pl and logP. For solution formulations at various stages of discovery studies, dose analysis is essential, and for efLcacy assessment and toxicology studies, chemical stability for the... 

Biorelevant media, such as FaSSIF and FeSSIF, that model composition of the gastric and intestinal contents before and after meal intake... 

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