Dissolution Testing of Sublingual Tablets: A Novel In Vitro Method

Abstract

Abstract. In the sublingual (SL) cavity, compared with the gastrointestinal tract, tablets are subjected to minimal physiological agitation, and a limited volume of saliva is available to facilitate disintegration and dissolution. None of the official compendial dissolution apparatuses and methods simulate these SL conditions. In this study, a custom-made dissolution apparatus was constructed, and a novel in vitro method that simulates SL conditions was evaluated. Several epinephrine 40 mg SL tablet formulations under development and two commercial SL tablets, isosorbide dinitrate 5 mg and nitroglycerin 0.6 mg, were studied. The dissolution medium was 2 mL of distilled water at 25°C. Dissolution was measured at 60 and 120 s. The novel in vitro method was validated for accuracy, reproducibility, and discrimination capability, and was compared with the official US Pharmacopeia (USP) dissolution method using apparatus 2 (Paddle). The data obtained following the novel in vitro method were accurate and reproducible. This method was capable of detecting minor changes in SL formulations that could not be detected using other in vitro tests. Results from the official USP dissolution method and our novel in vitro method were significantly different (p<0.05). Results reflecting the dissolution of rapidly disintegrating tablets using simulated SL conditions were obtained using the novel in vitro dissolution method.

Adrenaline (epinephrine) microcrystal sublingual tablet formulation: enhanced absorption in a preclinical model

“…These RDSTs contained no lactose or bisulfite and were quality control tested for tablet weight variation, content uniformity and friability using the harmonized United States Pharmacopoeia (USP) standards and criteria [23,24]. Tablet disintegration time was measured using a previously developed in‐vitro disintegration test to simulate the sublingual environment [18–21]…”

“…[23,24] Tablet disintegration time was measured using a previously developed in-vitro disintegration test to simulate the sublingual environment. [18][19][20][21] Adrenaline content was analysed using a reverse-phase HPLC system with ultraviolet detection (Waters Corp., Milford, MA, USA) according to the USP method for Epi injections. [25] In-vivo studies…”

“…The high vascularity of the sublingual mucosa and the low molecular weight of adrenaline facilitate rapid absorption directly into the venous circulation through the sublingual veins. [11,12,[14][15][16][17] The RDSTs are hard enough to withstand shipping and handling, yet disintegrate rapidly in vitro to release adrenaline in <30 s. [18][19][20][21] In previous preclinical studies, adrenaline 40 mg administered sublingually achieved plasma adrenaline concentrations similar to those reached after injection of adrenaline 0.3 mg in the thigh. [11,12,14] Relatively high adrenaline doses are needed when the sublingual route of administration is utilized in order to create the concentration gradient required and facilitate absorption.…”

Sublingual Diffusion of Epinephrine Microcrystals from Rapidly Disintegrating Tablets for the Potential First-Aid Treatment of Anaphylaxis: In Vitro and Ex Vivo Study

“…Previously, we developed Epi RDSTs that retain sufficient hardness to withstand shipping and handling but disintegrate rapidly (≤30 s) to release Epi (12)(13)(14)(15)(16). In a validated rabbit model, we demonstrated that the rate and extent of absorption after administration of an Epi 40 mg RDSTs was similar to the rate and extent of absorption after administration of Epi 0.3 mg intramuscular (IM) through an EpiPen the sublingual mucosa and achieve the required plasma epinephrine levels.…”

Influence of poloxmer on the dissolution properties of mosapride and its pharmaceutical tablet formulation

“…It is reasonable to have an in vitro method of testing dissolution that is sensitive to formulation factors that affect the solubility process and therefore, bioavailability. In recent years, the discriminatory capabilities and reliability of dissolution tests of tablets have attracted much attention [30] . In order to establish acceptance criteria and preview how alterations in manufacturing would affect bioavailability, different parameters were used to differentiate and identify the differences in formulations.…”