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

Lund, Kaare; Kito, Hirokazu; Skydtsgaard, Mette Blem; Nakazawa, Hiroshi; Ohashi-Doi, Katsuyo; Lawton, Simon

doi:10.1016/j.clinthera.2019.02.008

Cited by 16 publications

(16 citation statements)

References 32 publications

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“…Differences between the licensed 1-and 5-grass pollen SLIT products are evident. A recent report has implied that in vitro dissolution kinetics of SLIT tablets correlate with bioavailability and clinical efficacy [28]; however, it is clear that this is not the case, and in vitro dissolution rate cannot be used as a reliable indicator of clinical efficacy. Based on the current knowledge of the oral immune response, a formulation encompassing a very rapid dissolution may not be optimal for sublingual administration of allergens.…”

Section: Resultsmentioning

confidence: 99%

“…Grass group 5 major allergen content was measured by enzyme-linked immunosorbent assay using a proprietary monoclonal antibody against Phl p 5, after dissolution of either grass pollen SLIT tablet in a phosphate buffer approximating human saliva in pH, ionic strength and total protein content (but not containing salivary enzymes or any other components of saliva). Full recovery of the 1-grass pollen SLIT tablet allergen content was achieved after~15 s, whereas only~16% of Phl p 5 content was released from the 5-grass pollen SLIT tablet after 120 s (p < 0.0001 for comparison of released Phl p 5) [28]. It should be remembered that quantification of Phl p 5 can be affected by the specificity and sensitivity of the antibodies used for detection, and/or whether they are mono-or polyclonal antibodies; moreover, quantification of Phl p 1/grass group 1 major allergens has not been assessed for either SLIT tablet formulation.…”

Section: Tablet Dissolution and Allergen Releasementioning

confidence: 96%

“…Characteristic 1-grass pollen SLIT tablet 5-grass pollen SLIT tablet Administration [4,5] Perennial Pre-/coseasonal Dosing Optimal [8,9] Licensed [4,5] Not determined 75,000 SQ-T 300 IR 300 IR Tablet potency [7] 2,800 BAU 9,000 BAU Dissolution time in vitro [27,28] Physical disintegration of tablet To release ≥85% of allergenic activity 2 s 15 s…”

Section: Article Highlightsmentioning

confidence: 99%

“…Depending on the method used, in vitro dissolution assays of SLIT tablets can produce dramatically different results. Using a method advocated by the Japanese Pharmacopoeia, the 1-grass pollen SLIT tablet was shown to dissolve completely within 1 s versus incomplete dissolution of the 5-grass pollen SLIT tablet after 30 s, and this difference between dissolution times was significant (p < 0.001) [28]. Grass group 5 major allergen content was measured by enzyme-linked immunosorbent assay using a proprietary monoclonal antibody against Phl p 5, after dissolution of either grass pollen SLIT tablet in a phosphate buffer approximating human saliva in pH, ionic strength and total protein content (but not containing salivary enzymes or any other components of saliva).…”

Section: Tablet Dissolution and Allergen Releasementioning

confidence: 99%

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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: Resultsmentioning

confidence: 99%

Section: Tablet Dissolution and Allergen Releasementioning

confidence: 96%

Section: Article Highlightsmentioning

confidence: 99%

Section: Tablet Dissolution and Allergen Releasementioning

confidence: 99%

See 2 more Smart Citations

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

View full text Add to dashboard Cite

show abstract

“…In addition, a limitation of SLIT tablet occurs from its ingredient which consists of only one antigen [14]. It has been recently demonstrated that pharmaceutical SLIT-tablet formulations are also important and affects the efficacy with which allergen has delivered from the dry state of the tablet into a soluble form [16]. SLIT has a good safety and tolerability profile compared to SCIT owing to the lack of systemic exposure to intact allergens and low frequency of systemic allergic reactions [14].…”

Section: General Methods and Novel Approaches Of Administrationmentioning

confidence: 99%

Diverse Mechanisms of Allergen Specific Immunotherapy

Cevhertas

Лацин

Akdiş

et al. 2019

Vestn. Ross. univ. družby nar., Ser. Med.

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Allergen immunotherapy (AIT) is widely used to establish a tolerant immune response and it is currently the only disease modifying treatment. There are different routes to administer the allergen, including subcutaneous, sublingual, intralymphatic, epicutaneous, intradermal, and oral and local nasal allergen immunotherapy. Although the optimal administration route depends on the type of allergen, some patients remain unresponsive and so it is important to predict the outcome before and during treatment. Therefore, there is a need to identify candidate prognostic markers for allergen immunotherapy. Herein, we discuss the recent literature on the molecular mechanisms of AIT.

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Utility of silver birch and house dust mite extracts derived from licensed sublingual tablets for nasal allergen challenge

Olivieri,

Gil,

Stoenchev

et al. 2024

Clinical & Translational All

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BackgroundNasal allergen challenge (NAC) is used to investigate the effects of allergen exposure and assess treatment efficacy in allergic rhinitis (AR). This study aims to establish dose‐responses to NAC using licensed silver birch (SB) pollen and house dust mite (HDM) sublingual tablets as sources of the allergen extracts in participants with AR.MethodsSixteen volunteers with HDM‐induced perennial AR and 15 volunteers with SB pollen‐induced seasonal rhinitis underwent a graded up‐dosing NAC with extracts derived from HDM allergen (Acarizax®) and SB (Itulazax®) tablets, respectively. Total nasal symptom score (TNSS, range 0–12) and peak nasal inspiratory flow (PNIF) were recorded before, at 10 min and at the end of the NAC. The dose of each allergen that provoked a TNSS of at least 7 (“provoking dose 7”) in most allergic participants was identified. NACs using the “provoking dose 7” were performed on 5 non‐allergic individuals to test for irritant effects. The “provoking dose 7” of HDM extract was used in a subgroup of two SB allergic, non‐HDM allergic, volunteers, and vice versa for SB extract, to test for allergen specificity of the responses.ResultsMost patients experienced a TNSS of at least 7/12 at a median concentration of 1500 AU/mL for both SB pollen and HDM. The average decline in PNIF at this dose was 63.15% for SB and 63.99% for HDM. NACs using the 1500 AU/mL concentrations were performed on 5 non‐allergic individuals with no symptomatic or PNIF response. 1500 AU/mL of HDM extract produced no symptoms in SB allergics nor 1500 AU/mL SB extract in HDM allergics.ConclusionFor both SB and HDM extracts, the optimal allergen dose for NAC to cause a moderate‐severity response (“provoking dose 7/12”) was 1500 AU/mL. Licensed sublingual allergen tablets provide a readily available and inexpensive source of SB and HDM extracts for use in future interventional studies in AR.

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

Cited by 16 publications

References 32 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

Diverse Mechanisms of Allergen Specific Immunotherapy

Utility of silver birch and house dust mite extracts derived from licensed sublingual tablets for nasal allergen challenge

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