The Effective Allergenic Reactivity of House Dust Mite Sublingual Immunotherapy Tablets Is Determined by Tablet Formulation

Kito, Hirokazu; Du, Weibin; Nakazawa, Hiroshi; Lund, Kaare; Ohashi-Doi, Katsuyo

doi:10.1248/bpb.b18-00857

Cited by 6 publications

(3 citation statements)

References 11 publications

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“…Disintegration times were~1 s versus 45 s for the 12 SQ HDM and 300 IR HDM SLIT tablets, respectively (p < 0.0001). Complete release of Der f 1, Der p 1 and Der 2 from the 12 SQ-HDM SLIT tablet was obtained within 30 s, whereas for the 300 IR HDM SLIT tablet, soluble HDM major allergen content continued to increase over time, but did not reach complete release, even after 10 minutes [29,30]. In contrast, using an in vitro dissolution assay endorsed by the European Pharmacopoeia (Ph.…”

Section: Tablet Dissolution and Allergen Releasementioning

confidence: 95%

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

Canonica

Devillier

Casale

et al. 2019

Expert Review of Clinical Immunology

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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.

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Section: Tablet Dissolution and Allergen Releasementioning

confidence: 95%

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

Canonica

Devillier

Casale

et al. 2019

Expert Review of Clinical Immunology

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“…Major allergen content (Cry j 1, Der p 1, Der f 1, Der 2) was measured by ELISA. Total allergenic reactivity was measured by competition ELISA using a pool of human sera essentially as described (9,10). All procedure employed in the study were approved by the Ethics Committees of TORII Pharmaceutical Co., Ltd. according to the Clinical Research Ethical Guidelines.…”

Section: Methodsmentioning

confidence: 99%

Allergen Stability and Immunological Reactivity during Co-dissolution and Incubation of House Dust Mite and Japanese Cedar Pollen SLIT-Tablets

Watanabe¹,

Yamamoto²,

Matsuhara³

et al. 2020

Biological & Pharmaceutical Bulletin

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Japanese allergic subjects are commonly sensitized to both house dust mite (HDM) and Japanese cedar pollen (JCP) and combined treatment with sublingual immunotherapy (SLIT) tablets is desirable. However, mixing extracts of two non-homologous allergens may compromise allergen stability and affect the clinical outcome. Therefore, we investigated the stability of major allergens and total allergenic reactivity of HDM and JCP SLIT-tablets following dissolution in human saliva or artificial gastric juice. Two fast-dissolving freeze-dried SLIT-tablets were completely dissolved and incubated at 37°C. Major allergen concentrations and total allergenic reactivity were measured. After mixing and co-incubation of HDM and JCP SLIT tablets in human saliva for 10 minutes at 37°C, there were no statistically significant changes in major allergen concentrations. In addition, no loss of allergenic reactivity of the mixed two SLIT-tablet solutions was seen. In contrast, complete loss of allergenic reactivity and detectable major allergen concentrations occurred when the two SLIT-tablets were dissolved and incubated in artificial gastric juice. These results demonstrate that HDM or JCP major allergens and the total allergenic reactivity of both SLIT-tablets measured here remain intact after dissolution and co-incubation in human saliva, supporting the possibility of a dual HDM and JCP SLIT-tablet administration regimen if clinically indicated. The complete loss of allergenic reactivity after incubation in artificial gastric juice can furthermore be taken to indicate that the immunological activity of the allergen extracts contained in the two SLIT-tablets is likely to be lost or severely compromised upon swallowing.

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“…The dissolution study is an important study that gives an idea about the % of drug release at different time intervals (Kito et al, 2019). For SLT, super disintegrants affect the rate of dissolution.…”

Section: In Vitro Dissolution Studymentioning

confidence: 99%

Development of Nifedipine sublingual tablets using disintegrants as release modifiers

Swapna

Maheswaramma

Hemalatha³

et al. 2020

ijrps

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The current study mainly focused on treating cardiovascular diseases such as angina pectoris and chronic hypertension by modifying the existing commercial tablet available for Nifedipine. The limitation of Nifedipine is poor solubility, which comes under BCS class II drug category, which needs improvement in formulation to achieve better bioavailability. The objective of this research work is to enhance the oral bioavailability (first-pass metabolism in the liver (42–56%)) of Nifedipine by improving dissolution property. Sublingual fast dissolving tablets of Nifedipine formulated by sublimation method, designed to increase its disintegration time in the presence of saliva. This formulation is helpful for paediatric and geriatric patients who are unable to swallow the conventional tablet. Sublimation of camphor makes the tablet more porous and improve disintegration time as well. The direct compression method is used with different ratio of Croscarmellose Sodium (CS) and Sodium Starch Glycolate (SSG) as super disintegrants to formulate Nifedipine loaded Sublingual tablets. All formulations contain various ratio between super disintegrants and camphor, followed by the sublimation method. FTIR and DSC studies were conducted to investigate compatibility between drugs and disintegrants. Formulated tablets were subjected for precompression parameters, e.g., bulk density, tapped density, Carr’s index, Hausner’s ratio, angle of repose and for post-compression parameters, e.g. weight variation, thickness, hardness, friability, drug content, wetting time, disintegration time followed by dissolution study and found satisfactory as per IP.

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The Effective Allergenic Reactivity of House Dust Mite Sublingual Immunotherapy Tablets Is Determined by Tablet Formulation

Cited by 6 publications

References 11 publications

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

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

Allergen Stability and Immunological Reactivity during Co-dissolution and Incubation of House Dust Mite and Japanese Cedar Pollen SLIT-Tablets

Development of Nifedipine sublingual tablets using disintegrants as release modifiers

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