Formulation and Characterization of Orally Dissolving Thin Films containing the German cockroach Blatella germanica (Bla g 2) Allergen

Abstract

Allergy and asthma are among the most common chronic diseases of childhood. Cockroach allergy is an important contributor to asthma morbidity, with a prevalence of 17 to 41%. Immunotherapy has been shown to be an effective treatment for other allergies that contribute to asthma, but several factors have limited its use for cockroach allergy. In this work, a sublingual immunotherapy (SLIT) formulation of orally dissolving thin film has been developed for the treatment of hypersensitivity to the German cockroach Bla g 2 allergen. The formulation allows for the incorporation of up to 25 μg/film of the allergen protein, and the film's mucoadhesiveness prolongs the effect of the allergen with the potential for enhanced efficacy. The potency and dose uniformity of the SLIT formulation were characterized by enzyme-linked immunosorbent assay (ELISA), and other physicochemical properties were evaluated by spectroscopic or mechanistic methods. The films were uniform in weight and thickness, and demonstrated substantial physical strength to allow easy manipulation during manufacturing and dosing. The dosage uniformity, in vitro disintegration and in vitro dissolution profiles of the films were within the acceptance criteria in the United States Pharmacopeia. The developed SLIT methodology possesses the potential to significantly improve immunotherapy for both food and inhalant allergies in adults and children.

Keywords: Bla g 2; Cockroach; ELISA; drug delivery; immunotherapy; thin film.

Figure 1

The appearance and dimensions of the oral dissolving thin film strip with 25 μg of Bla g 2 allergen loading.

Figure 2

Typical Stress-Strain curve of SLIT thin films containing maximum (25 μg/filmstrip) aqueous cockroach protein extract and blank filmstrip without any allergen extract.

Figure 3

In vitro dissolution profile of sublingual immunotherapy filmstrips (n = 6). The results were quantitated against the standard curve for the total protein extract released.

Figure 4

Decomposition profile of SLIT thin filmstrips under the accelerated stability test condition (40°C and 75% RH) over two weeks. The air-dried group of the filmstrips contained 5% excess water (●); oven-dried group contained 3% excess water (■), and lyophilized group of filmstrips contained no excess water (▲). Each data point is the average of two independent determinations of Bla g 2 allergen using ELISA.