The Importance of Tablet Formulation on Allergen Release Kinetics and Efficiency: Comparison of Freeze-dried and Compressed Grass Pollen Sublingual Allergy Immunotherapy Tablet Formulations.

PURPOSE: Efficient delivery of allergens to the sublingual mucosa is a prerequisite for successful sublingual immunotherapy (SLIT) for allergy, and in order to become available to immune-competent cells embedded in the sublingual mucosa, allergens need to be delivered in a soluble form. Delivery of solubilized allergens poses a particular challenge for tablet-based allergy immunotherapy, in which allergens are administered under the tongue in the form of dry tablets and need to be dissolved rapidly in a small volume of saliva, with little or no agitation. The purposes of this article were to compare the properties of 2 different pharmaceutical SLIT-tablet formulations, freeze-dried and compressed, and to examine how the tablet formulation affects the efficiency with which allergen is delivered from the dry state of the tablet into soluble form. METHODS: Two SLIT-tablet formulations, both indicated for grass pollen allergic rhinitis and containing grass pollen extract as the active ingredient, were examined with regard to tablet disintegration times, allergen dissolution kinetics, dependency on solvent volume and agitation, and the achieved recovery of the grass allergen content in soluble form with each tablet. FINDINGS: The freeze-dried and the compressed SLIT-tablet formulations differed markedly with respect to efficiency of allergen release. The freeze-dried tablet disintegrated faster and released grass allergen into solution with a release rate higher than that of the compressed formulation and, in contrast to the compressed formulation, achieved full recovery of the allergen content in soluble form in a small volume of solvent. IMPLICATIONS: Rapid and complete release of soluble allergen in a small volume of solvent, as demonstrated by the freeze-dried formulation, are key elements of efficient sublingual allergen delivery by SLIT-tablets. Complete allergen release means that the full allergen dose of the tablet is recovered from the tablet and made available to the sublingual immune system in soluble form, and rapid release ensures that the immune system becomes exposed to the highest possible dose of soluble allergen for the maximal duration before swallowing. In contrast, a SLIT-tablet formulation that provides incomplete and slower allergen release will likely require a higher allergen content compared to the more efficient formulation, in order to achieve the same dose of soluble allergen, consequently leading to an excess load of allergen that becomes swallowed without having been made immunologically available.

Clinical characterization and IgE profiling of birch (Betula verrucosa)--allergic individuals suffering from allergic reactions to raw fruits and vegetables.

BACKGROUND: Hypersensitivity to raw fruits and vegetables is often associated with respiratory allergy to birch (Betula verrucosa) pollen and is considered to be the most prevalent form of food allergy in adults sensitized to birch pollen. OBJECTIVE: The aim of the study was to investigate the association of clinical allergy and IgE profiles in individuals with birch pollen allergy and hypersensitivity to raw fruits and vegetables. METHODS: A total of 59 adults with clinical and skin prick test confirmed birch pollen allergy were included in the study. All the subjects were interviewed by using a structured questionnaire and were examined in vivo by the open test, with the appropriate fruits and vegetables. ImmunoCAP and ImmunoCAP ISAC were used as in vitro diagnostics to assess sensitization profiles for each individual, and principal components analysis was used to analyze the IgE data sets. RESULTS: Of 59 individuals, 54 (92%) had positive prick-prick test with raw potato, carrot, apple, and/or hazelnut, and the skin prick test was always positive when the corresponding skin challenge was defined as positive. Specific IgE in the ImmunoCAP and inhibition assays with rMal d 1 and rBet v 1 demonstrated that Bet v 1 is driving the sensitization against pathogenesis related-10 proteins. However, positive IgE in vitro results could not be used to predict clinical reactivity to raw fruits and vegetables. CONCLUSIONS: The present study showed that component-based IgE profiling does not enhance the diagnostic potential in case of pollen-food syndrome, which may be associated with other as yet unidentified components.