Clinical efficacy of sublingual immunotherapy tablets for allergic rhinitis is unlikely to be derived from in vitro allergen-release data

Abstract

Introduction: Allergen bioavailability underpins the efficacy and safety of SLIT tablets. Three productrelated factors are likely to influence this: tablet potency, formulation and sublingual holding time. Areas covered: Tablet formulation determines the rate and extent of solubilized allergen release. Using validated in vitro dissolution assays, the two licensed grass pollen SLIT tablets are shown to release ≥85% of their total allergenic activity within several minutes. Sublingual holding time affects the contact duration between solubilized allergens and sublingual tissue. Maximal uptake of allergens by sublingual tissue requires~5 minutes, with little uptake occurring within the first minute. A higher potency tablet with longer sublingual holding time would provide higher bioavailability, while faster rates of allergen release in vitro are unlikely to translate to a greater increase in bioavailability. Differences in dissolution times cannot serve as a surrogate of in vivo bioavailability, and are not related to differences in efficacy at the marketed tablet dosages. Rapid in vitro dissolution is likely not a key requirement for inducing a potent immune response. Expert opinion: In vitro dissolution cannot predict the clinical efficacy of SLIT tablets but could be important in immune tolerance and safety. In addition, a discontinuous administration regimen may have benefits for adherence and cost without compromising efficacy.

Update about Oralair® as a treatment for grass pollen allergic rhinitis

“…The freeze-dried allergen extracts are formulated with inactive ingredients (mannitol, microcrystalline cellulose, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate, and lactose monohydrate) to generate the final compressed tablet. 27 , 37 This final formulation was designed to deliver a sustained allergen release across the sublingual mucosa over 2–3 minutes, with >90% of total allergenic activity released within 2 minutes. 37 Maximal allergen absorption requires 5 minutes, 38 as earlier swallowing may reduce allergen uptake by mucosal antigen presenting cells (APCs).…”

“… 27 , 37 This final formulation was designed to deliver a sustained allergen release across the sublingual mucosa over 2–3 minutes, with >90% of total allergenic activity released within 2 minutes. 37 Maximal allergen absorption requires 5 minutes, 38 as earlier swallowing may reduce allergen uptake by mucosal antigen presenting cells (APCs). 37 Following swallowing, the polypeptide/peptide allergen extracts undergo proteolytic degradation in the GI tract with no significant systemic exposure; as systemic allergen absorption is limited, no formal pharmacokinetic studies have been required or performed.…”

“… 37 Maximal allergen absorption requires 5 minutes, 38 as earlier swallowing may reduce allergen uptake by mucosal antigen presenting cells (APCs). 37 Following swallowing, the polypeptide/peptide allergen extracts undergo proteolytic degradation in the GI tract with no significant systemic exposure; as systemic allergen absorption is limited, no formal pharmacokinetic studies have been required or performed. 27 , 37 …”

“… 37 Following swallowing, the polypeptide/peptide allergen extracts undergo proteolytic degradation in the GI tract with no significant systemic exposure; as systemic allergen absorption is limited, no formal pharmacokinetic studies have been required or performed. 27 , 37 …”

Sublingual Boosting with a Novel Mucoadhesive Thermogelling Hydrogel Following Parenteral CAF01 Priming as a Strategy Against Chlamydia trachomatis

“…It has a gel strength of 0.7 N, a mucoadhesion and adhesion work of 1.24 and 1.74 mJ respectively, and a cohesion of 0.2. Finally, it releases up to 41.11% of the protein at 5 min, quick enough to ensure vaccine absorption in a few minutes [ 37–39 ] and avoids formulation leakage by swallowing. OGEL has long‐term stability at 4 °C (Table 2) and statistically significant differences could not be found between OGEL freshly prepared and after 1‐year storage at 4 °C ( p < 0.05).…”