**6. Drug release and the justification of dispersion test for nanoformulations**

*In vitro* release studies assess the ability of lipid‐based nanoformulations to disperse into various types of media and to evaluate whether the drug partitions from the vehicle into the aqueous medium. It can estimate how much drug will be in solution before absorption thus predicts the fate of the drug *in vivo*. A range of biorelevant dissolution test media and experi‐ mental methodologies has been developed by Dressman's group that have established application in drug release studies from lipid‐based oral formulations [38, 39].

Technically, it is difficult to characterize drug release from emulsions *in vitro*, particularly under sink condition. Since solubility of the drug in sink phase may be poor, large volumes of aqueous content may be needed to maintain the sink conditions. It is hard to separate the oil droplets due to their smaller size from the dissolved or released drug in the sink solution levy. In a previous study, our group has conducted an *in vitro* dissolution of anti‐histaminic drug, cinnarizine (CN, week base) from various SNEDDS systems and commercial product Stuger‐ on® tablet [4]. Dissolution was carried out in simulated gastric fluid (SGF, pH 1.2) for first 2 h and subsequently shifted into simulated intestinal fluid (SIF, pH 6.8) for another 2 h.

**Figure 3.** Dissolution profiles of cinnarizine SNEDDS 1 [MCT/MCDM/T85 (25/25/50)], SNEDDS 2 [MCT/MCM/T85 (25/25/50)] and Stugeron® tablets. Data are expressed as mean ± S.E, n = 3. \*\*Abbreviations: MCT—medium‐chain tri‐ glycerides (M810); MCDM—mixture of medium‐chain di‐ and monoglycerides (I988); MCM—medium‐chain mono‐ glycerides (I308); T85—Tween 85.

In SGF, all the SNEDDS showed superior dissolution profiles with respect to Stugeron® tablet (**Figure 3**). At 15 min, Stugeron® tablet managed to release only 66.5% drug in solution where the optimal formulations were able to release 84–95% drug in solution. This indicates the ability of these formulations to provide more efficient and rapid release of CN with respect to the marketed tablet. Upon shifting from SGF to SIF, Stugeron® showed significant precipitation (87–92% precipitated), while the SNEDDS were able to hold high amount of CN (78–93%) in solution (**Figure 3**). This finding suggests the immense need for developing a SNEDDS that could enhance the drug dissolution profile and resist the sharp pH‐dependent changes particularly for week bases.

A standard USP dissolution apparatus is suitable for the establishment of a dispersion test, but emphasis should be on precipitation rather than dissolution [4]. This is why, dynamic disper‐ sion test is highly considered for the prediction of whether precipitation is likely to occur prior to digestion. In the dispersion study, samples are removed from the dispersion vessel at various intervals for at least 24 h and analyzed to determine the likelihood of precipitation during GI transit. Dispersion testing is vital for LFCS Types III and IV formulations (produce SNEDDS), which may loss solvent capacity on dispersion due to migration of water soluble components into the bulk aqueous phase. Care is needed in the design of lipid‐based nanoformulations to ensure that the precipitation of the drug is minimized.
