This minireview describes methods to evaluate bioequivalence (BE) between solid oral formulations that act locally in the gastrointestinal tract. These pharmaceuticals are categorized into several groups depending on the site of action and the type of formulation. Complex relationships between dissolution, absorption, and therapeutic effect in some controlled-release mesalamine formulations for ulcerative colitis emphasize the importance of setting appropriate bioequivalence studies. Limited values of blood concentration pharmacokinetic (PK) data emphasize the relevance of combining multiple in vitro and in vivo methods for the BE study of these pharmaceuticals. Setting an appropriate in vitro binding study is significantly important for some therapeutics (e.g., spherical adsorptive carbon) that are difficult to get sufficient information on in PK and pharmacodynamic (PD) studies. Some approaches combining reduced formulation difference (Q1, Q2) and in vitro studies have been introduced in some European and US guidelines and guidance.

Solid pharmaceutical formulations for oral use (granule, tablet) with improved solubility of poorly water-soluble cyclosporine (Cyc) were designed using the combination technique consisting of wet-milling and the drop freeze-drying (DFD) process. The particles of Cyc were dispersed in the aqueous solution composed of hydroxpropyl cellulose as a milling promotor and sodium lauryl sulfate as a dispersion stabilizer, and pulverized into nanometer-sized particles by the wet beads milling technique. Subsequently, the resultant aqueous Cyc nanosuspension with co-dissolving mannitol (MNT) was dropped into liquid nitrogen and freeze-dried to obtain the dried granules. The granules with a wide content range (6.67-47%) could be prepared by adjusting the amount of MNT added. Furthermore, the tablets containing 10 mg of Cyc were manufactured by directly compressing the granules. The kinetic dispersing test indicated that the granules and tablets prepared through these sequential processes had self-dispersion characteristics of Cyc particles. When they were placed in aqueous phase, submicron-sized Cyc particles were spontaneously dispersed. As a result, the granules showed an excellent dissolution behavior of more than 95% at 10 min. On the other hand, the tablets showed fast and high dissolution behavior of more than 80% at 30 min despite no added disintegrant. The outcome of this research would be a new platform technology for improving solubility, which would enable the development of solid formulations with poorly absorbable drugs.

The adsorption of amlodipine besylate (AML) to microcrystalline cellulose (MCC) and corn starch suspended in aqueous solution was investigated herein. The adsorption of AML to experimental tools was assessed in a preliminary study, and the results obtained showed the adsorption of AML in water to glass, but not to polypropylene tools. Adsorption to glass tools was prevented by using 50% methanol solution. The adsorption isotherm of AML to MCC suspended in solution at 37˚C was the Langmuir type. Vmax, the adsorbed amount of drug per unit weight of MCC, and k, a constant, were 8.60×10⁻³ mmol/g MCC and 3.57 L/mmol, respectively. The adsorption isotherm of AML to corn starch suspended in solution at 37˚C was the Freundlich type. The Freundlich constants, k and 1/n were 0.729 and 3.57×10⁻³ mmol/g corn starch, respectively. The percent adsorption of AML to MCC and corn starch was lower in buffer and 0.9% NaCl solutions than in water. In buffer and 0.9% NaCl solutions, the percent adsorption to corn starch was higher than that to MCC. These results indicate that when the AML dissolution rate from orally disintegrating tablets in the mouth is the same, differences in the amount of corn starch in tablets affect the concentrations of solutions in the mouth due to adsorption. This difference may be detected by patients by a change in the taste of tablets.