Sublingual Research Articles

A Cost-Utility Analysis of SQ® Tree SLIT-Tablet versus Placebo in the Treatment of Birch Pollen Allergic Rhinitis from a Swedish Societal Perspective.

Allergic rhinitis (AR) is an immunoglobulin E antibody-mediated inflammatory condition that arises in response to inhaled allergens such as pollen. Pollens from trees in the birch homologous group are the most common allergenic tree pollens in Northern and Central Europe and North America. SQ® Tree SLIT-Tablet (ITULAZAX®) is a sublingual immunotherapy tablet indicated for moderate-to-severe AR and/or conjunctivitis induced by pollen from the birch homologous group. The present analysis evaluated the cost-utility of treating adults with AR with SQ Tree SLIT-Tablet versus placebo, both in combination with symptom-relieving medications, from a Swedish societal perspective. A model was developed to evaluate changes in cost and quality of life associated with using SQ Tree SLIT-Tablet relative to placebo in an adult population of individuals with AR. The model captured costs associated with symptom-relieving medications, healthcare professional interactions, SQ Tree SLIT-Tablet, and indirect costs arising from absenteeism and reduced workplace productivity. The analysis was conducted over 10 years with costs captured in 2021 Swedish Krona (SEK) and future costs and effects discounted at 3% per annum. One-way and probabilistic sensitivity analyses were conducted. Treatment with SQ Tree SLIT-Tablet resulted in an improvement of 0.041 quality-adjusted life years (QALYs) over 10 years versus placebo. From a Swedish societal perspective, costs increased by SEK 9077 over the same period, resulting in an incremental cost-utility ratio of SEK 223,445 per QALY gained. One-way sensitivity analysis showed that the model was most sensitive to assumptions around the disease-modifying effect of SQ Tree SLIT-Tablet. SQ Tree SLIT-Tablet improved quality of life in moderate-to-severe AR and/or conjunctivitis induced by pollen from the birch homologous group in Sweden, with only a modest increase in societal costs over a medium-term time horizon, representing good value for money at a willingness-to-pay threshold of SEK 700,000 per QALY.

Anaphylaxis is Uncommon in Clinical Trials of Sublingual Immunotherapy Tablets as Identified by a Standardized Algorithm

There is no universal consensus definition for anaphylaxis in sublingual immunotherapy (SLIT) trials. Therefore, the reported incidence varies considerably. An algorithm in the Standardized MedDRA Query (SMQ) was used to identify anaphylaxis in SLIT-tablet trials.

Onset of Clinical Effect with Sublingual Immunotherapy Tablets for Allergic Rhinoconjunctivitis

Knowledge is limited regarding the minimum duration of time needed to induce allergen-specific tolerance and clinical improvement with immunotherapy for allergic rhinitis/conjunctivitis. Onset of clinical effect was evaluated for grass, ragweed, tree, and house dust mite (HDM) sublingual immunotherapy (SLIT)-tablets.

Relationship between Experience of Antepartum Intervention and Posttraumatic Stress Symptoms Following Childbirth: A Prospective Study

Background: Childbirth is an important event in a woman’s life. Adverse childbirth experiences may lead to negative psychological reactions and disturb the mother’s mental health during the postpartum period. Objective: This prospective study aimed to assess the relationship between experiences of antepartum intervention and post-traumatic stress symptoms in mothers following childbirth. Methods: The study sample comprised 176 Iranian women, who were under assessment for 8 weeks postpartum. Current Post-Traumatic Stress Disorder symptoms (PTSD) were assessed through the Impact of Events Scale-Revised (IES-R) questionnaire. Data were analyzed using SPSS software (Version 19.0), and the adjusted odds ratios (ODs) were estimated by binary logistic regression. Results: Based on the obtained results, 38.3% (N = 62) of the women appeared to be at risk of developing PTSD symptoms. The mean ± SD score of PTSD symptoms was obtained at 22.51 ± 12.04 (0-65). The results showed that women in the PTSD group underwent more obstetric interventions (P = 0.002) and experienced more childbirth pain (P = 0.048), compared to women without PTSD, during childbirth. Insertion of sublingual or vaginal prostaglandin tablets, experiencing episiotomy incision, perineal/labial/vaginal sutures, and artificial rupture of amniotic membranes correlated significantly with PTSD symptoms (P < 0.05). The results of binary logistic regression analysis confirmed that the rate of obstetric interventions was the significant predictor of PTSD after childbirth (OD = 1.284; P = 0.008). Conclusion: The findings of the present study indicate that the enhanced understanding of healthcare providers of obstetric intervention consequences may prevent postpartum PTSD through the provision of physiological delivery and supportive care during labor.

Industry update, December 2022.

Industry update, December 2022.

Allergen immunotherapy in house dust mite-associated allergic rhinitis: efficacy of the 300 IR mite tablet

AbstractBackgroundA perennial house dust mite-associated allergic rhinitis has a major impact on the quality of life of patients and is associated with a high socioeconomic burden. The most common symptoms of allergic rhinitis include a runny nose and nasal congestion, sneezing, itching of nose, mouth and/or throat, and/or ocular symptoms. Affected patients often develop allergic bronchial asthma. Therapy options for allergic rhinitis include allergen avoidance, symptomatic treatment, and allergen immunotherapy. Allergen immunotherapy is the only disease-modifying treatment that can permanently alleviate the symptoms of allergic rhinitis. In July 2021, a new sublingual mite tablet was approved in Germany.MethodsThis review summarizes clinical studies on the 300 IR (index of reactivity) mite tablet in adolescents and adults with house dust mite-associated allergic rhinitis and presents the results.ResultsIn the phase II and phase III studies considered here, different dosages of the mite tablet were investigated. The 300 IR mite tablet showed the best benefit–risk profile and has been approved in Europe, Japan, South Korea, Australia, and New Zealand for the treatment of house dust mite-associated allergic rhinitis.ConclusionAllergen immunotherapy with the 300 IR mite tablet is an effective treatment that relieves allergic symptoms, reduces the need for symptomatic medication, and improves the quality of life in both adults and adolescents with house dust mite-associated allergic rhinitis. At the same time, treatment with the 300 IR mite tablet is well tolerated. Mild to moderate reactions at the application site subside after a few days.

Colorectal and bladder prokinetic activity of [Lys5, MeLeu9, Nle10]-NKA(4-10) after intranasal or sublingual delivery in dogs.

The feasibility of eliciting defecation and urination after intranasal (IN) or sublingual (SL) delivery of a small peptide NK2 receptor agonist, [Lys5, MeLeu9, Nle10]-NKA(4-10), was examined using prototype formulations in dogs. In anesthetized animals, administration of 100 or 300 µg/kg IN or 2.0-6.7 mg/kg SL increased colorectal peak pressure and area under the curve. Peak bladder pressure was also increased at the same doses, and this was accompanied by highly efficient voiding at normal physiological bladder pressure. The onset of these effects was rapid (≤2.5 min), and the primary contractions lasted ∼25 min, returning to baseline in <60 min. Slight hypotension lasting a few minutes and causing<10% change from baseline was detected after higher doses and was statistically significant after only 100 µg/kg IN. In conscious dogs, there was a dose-related increase in voiding responses and reduction in the latency to urinate and defecate after 300 and 1000 µg/kg IN; emesis was also observed at these doses. SL administration of 6.7 mg/kg induced urination within 10 min, but not defecation or emesis. These findings support the feasibility of developing a convenient dosage form of small peptide NK2 receptor agonists as on-demand defecation or urination therapies.

Identification of Closed Linear Epitopes in S1-RBD and S2-HR1/2 of SARS-CoV-2 Spike Protein Able to Induce Neutralizing Abs.

SARS-CoV-2 has evolved as several variants. Immunization to boost the Ab response to Spike antigens is effective, but similar vaccines could not enhance Ab efficacy enough. Effective Ab responses against the human ACE2 (hACE2)-mediated infection of the emerging SARS-CoV-2 variants are needed. We identified closed linear epitopes of the SARS-CoV-2 Spike molecule that induced neutralizing Abs (nAbs) against both S1-RBD, responsible for attachment to hACE2, and S2-HR1/2, in convalescents and vaccine recipients. They inhibited a pseudo-virus infection mediated by the hACE2 pathway. The epitope sequences included epitopes #7 (aa411-432), #11 (aa459-480) and #111 (aa1144-1161), in S1-RBD and S2-HR2. Epitope #111 was conserved in Wuhan and variant strains, whereas #7 and #11 were conserved in Wuhan carried mutations K417N and S477N/T478K in Omicron BA.4/5. These mutations were recognized by the original epitope-specific Abs. These epitopes in RBD and HR2 neither contained, nor overlapped with, those responsible for the antibody-dependent enhancement of the SARS-CoV-2 infection. The sublingual administration of multiple epitope-conjugated antigens increased the IgG and IgA Abs specific to the neutralizing epitopes in mice pre-immunized subcutaneously. The findings indicated that S1-RBD and S2-HR2 epitopes were responsible for pseudo-virus SARS-CoV-2 infections and that sublingual boosts with multiple epitope-conjugated antigens could enhance the protection by nAbs of IgG and IgA against infection by a wide range of variants.

Mechanical bacterial lysate enhances antimicrobial barrier mechanisms in human airway epithelial cells.

Polyvalent mechanical bacterial lysate is effective in the prevention of respiratory tract infections, although its mechanism of action is not entirely elucidated. Because epithelial cells constitute the frontline defense against infections, we investigated the molecular mechanisms of innate response exerted by bronchial epithelial cells in the presence of polyvalent mechanical bacterial lysate. By using primary human bronchial epithelial cells, we observed that polyvalent mechanical bacterial lysate was able to increase the expression of cellular adhesion molecules such as ICAM-1 and E-cadherin, as well as the expression of amphiregulin, a growth factor able to support human bronchial epithelial cell proliferation. Remarkably, polyvalent mechanical bacterial lysate promoted in human bronchial epithelial cells the de novo expression of human β-defensin-2, a major antimicrobial peptide, conferring them a direct antimicrobial activity. Moreover, polyvalent mechanical bacterial lysate-stimulated human bronchial epithelial cells provided signals for increased IL-22 production by innate lymphoid cells via IL-23, which could further contribute to the release of antimicrobial peptides by epithelial cells. In agreement with these in vitro data, the concentration of both IL-23 and antimicrobial peptides (human β-defensin-2 and LL-37) increased in the saliva of healthy volunteers after sublingual administration of polyvalent mechanical bacterial lysate. Altogether, these results indicate that polyvalent mechanical bacterial lysate administration might support mucosal barrier integrity and promote mechanisms of antimicrobial activity in airway epithelial cells.

Minimization of ragweed allergy immunotherapy costs through use of the sublingual immunotherapy tablet in Canadian children with allergic rhinoconjunctivitis

BackgroundAllergy immunotherapy (AIT), in the form of subcutaneous immunotherapy (SCIT) with alum-precipitated aqueous extracts, SCIT with a modified ragweed pollen allergen tyrosine adsorbate (MRPATA; Pollinex®-R), or a sublingual immunotherapy (SLIT)-tablet are options for the treatment of ragweed pollen allergic rhinoconjunctivitis (ARC) in Canadian children. A cost minimization analysis evaluated the economic implications of the use of the ragweed SLIT-tablet vs SCIT in Canadian children with ragweed ARC.MethodsA cost minimization analysis was conducted comparing the short ragweed SLIT-tablet, 12 Amb a 1-U, preseasonally with preseasonal ragweed SCIT, annual ragweed SCIT, or MRPATA. The analysis was conducted over a time horizon of 3 years from a public payer perspective in Ontario and Quebec. Resources and costs associated with medication and services of healthcare professionals were considered for each treatment. The resource and cost input values for the model were obtained from published literature and validated by Canadian clinical experts in active allergy practice. A discount rate of 1.5% was applied. Several scenario analyses were conducted to determine the impact of many of the key base case assumptions on the outcomes.ResultsOver the total 3-year time horizon, the ragweed SLIT-tablet had a potential cost savings of $900.14 in Ontario and $1023.14 in Quebec when compared with preseasonal ragweed SCIT, of $6613.22 in Ontario and $8750.64 in Quebec when compared with annual ragweed SCIT, and $79.62 in Ontario and $429.49 in Quebec when compared with MRPATA. The ragweed SLIT-tablet had higher drug costs compared with the other AIT options, but lower costs for healthcare professional services. The lower costs for healthcare professional services with the ragweed SLIT-tablet were driven by the need for fewer office visits than SCIT. Scenario analysis indicated that costs were most impacted by including societal costs (e.g., costs associated with patient/caregiver travel and time lost). The potential cost savings of the ragweed SLIT-tablet versus SCIT and MRPATA was maintained in most scenarios.ConclusionsIn this cost minimization analysis, the ragweed SLIT-tablet provided estimated cost savings from a public payer perspective for the treatment of ragweed ARC in Canadian children compared with SCIT or MRPATA.

Highly Porous and Drug-Loaded Amorphous Solid Dispersion Microfiber Scaffolds of Indomethacin Prepared by Melt Electrowriting

Melt electrowriting (MEW) is an additive manufacturing technology enabling the production of highly porous microfiber scaffolds, suggested in particular for use in biomedical applications, including drug delivery. Indomethacin (IND) is a nonselective anti-inflammatory drug, for which sublingual delivery could offer advantages such as rapid absorption by the veins in the mouth floor while overcoming the side effects of peroral delivery such as damage to the gastrointestinal mucosa barrier. This study introduces MEW as a processing method to obtain rapid-dissolving drug-releasing scaffolds, containing IND as a model drug, for sublingual drug delivery applications. For this, an amorphous solid dispersion (ASD) of IND in combination with a poly(2-oxazoline)-based amphiphilic triblock copolymer excipient is introduced, enabling ultra-high drug loading. We prepared highly porous, melt electrowritten drug-loaded scaffolds with different polymer/IND w/w ratios up to 1:2 and assessed their morphology, amorphicity, and IND release rate. The results show completely amorphous dispersion of the polymer and drug after MEW processing resulting in smooth and uniform fibers and rapid dissolution of the drug-loaded scaffold. These first water-soluble melt electrowritten IND-loaded microfiber scaffolds break ground as a model for rapid sublingual delivery of ultra-high drug-loaded ASDs.

Sublingual Immunotherapy Tablets for Grass Allergy-Induced Rhinoconjunctivitis

Sublingual Immunotherapy Tablets for Grass Allergy-Induced Rhinoconjunctivitis

Evaluation of the sedative effect of sublingual lorazepam versus placebo in patients underwent endoscopy: a double-blind, randomized controlled clinical trial.

Digestive endoscopy (DE) is uncomfortable for most patients. Lorazepam is a potent benzodiazepine with anxiolytic and sedative effects. This study aims to determine the sedative effect of sublingual lorazepam versus placebo as a premedication in patients who underwent DE. This is a mono-center, double-blind, and randomized controlled trial. A lorazepam sublingual tablet was made by researchers and physical tests were done on it, then the double-blind placebo-controlled trial was done to investigate the efficacy of 2 mg sublingually administered lorazepam as a premedication for endoscopy. Lorazepam or a placebo tablet was administered sublingually 30 min before the endoscopy. The patients, nurses, and physicians were blinded to the patient group. The depth of sedation was evaluated according to the American Society of Anesthesiology. In all, 116 patients were randomly assigned to take either lorazepam (n = 58) or a placebo (n = 58). The results of physical properties tests were acceptable according to United States Pharmacopeia. There were no statistical differences between groups regarding age and gender. In the lorazepam group, 75.8% of patients showed mild sedation, and 24.2% of patients showed no sedation. All of the patients in the placebo had no sedation (p = 0.001). Time of procedure (p < 0.001), intraoperative O2 saturation (p < 0.001), intraoperative heart rate (p < 0.001), and intraoperative blood pressure (p < 0.001) were significantly lower in the lorazepam group. No significant or dangerous side effects were observed except a bit of giddiness and dizziness. The results of this study showed that prescription of sublingual lorazepam 25-30 min before endoscopy provided mild sedation. IRCT201611039014N130 (05/11/2016); https://en.irct.ir/trial/9568.

Clinical Efficacy of Sublingual Specific Immunotherapy in Children with Allergic Rhinitis and its Impact on their Inflammatory Factors and Immune Function

The main objective of this study is to analyze the effects of sublingual specific immunotherapy and conventional drug therapy on inflammatory factors and immune function in children with allergic rhinitis. The research subjects were divided into three groups, group A received sublingual administration of dust mite drops, group B received routine treatment such as passive intervention with topical hormones, antihistamines and nasal irrigation and group C received sublingual administration of dust mite drops and on the basis of drop therapy, conventional treatments such as topical and systemic use of corticosteroids, antihistamines and anti-leukotriene’s are combined. Comparison was done among the three different sets of indicators. After treatment, the allergic rhinitis symptom score, visual analog scale score and inflammatory factor index levels in the three groups were calculated. The score was lower in group A than in group B and lower in group C than in group A. Adverse reactions were lowest in group A and highest in group C. After treatment, the levels of whole blood cluster of differentiation 4+, cluster of differentiation 4+/cluster of differentiation 8+ cells and serum immunoglobulin E were lower in group C than group A, and lower in group B than group A. The cluster of differentiation 8+ index was highest in group C and lowest in group B. Sublingual specific immunotherapy is effective and safe for children with allergic rhinitis.

PS-BPC02-7: RADIAL-DIGITAL PULSE WAVE VELOCITY: STIFFNESS OF SMALL CONDUIT ARTERIES INCREASES AFTER NITROGLYCERIN ADMINISTRATION

Objective: The alteration of the physiological stiffness gradient within larger vessels would increase the transmission of greater pulsatility to the microcirculation, thus explaining the damage to the pressure-sensitive organs. We aimed to describe the response of small conduit arteries of the hand (radial-digital PWV, rd-PWV) following the pharmacological alteration of the stiffness gradient using nitroglycerin. Design and method: Simultaneous application of piezoelectric sensors (Complior) at the level of the carotid (c), the radial artery (r) and the tip of the index finger (d) was used to calculate the rd-PWV by the following formula (rd-PWV = cd-cr direct distances/cd-cr transit times). Rd-PWV was obtained before and 4 minutes after a sublingual administration of 0.4 mg of NTG, in healthy adults (controls, n = 36) and patients with moderate chronic kidney disease (CKD, n = 30). Changes in arterial stiffness pre-post NTG and comparisons between the two groups were analyzed respectively with paired or independent samples t-tests. Results: Compared to controls, the CKD group was older (69 ± 15 years vs. 41 ± 20 years) and more hypertensive. Despite similar cd-PWV and cr-PWV, rd-PWV was significantly lower in CKD than in controls (3.6 ± 1.4 m/s vs. 4.5 ± 1.8 m/s, p = 0.024), but this difference faded (p = 0.145) after adjustment for age. Post NTG, brachial blood pressure decreased and heart rate increased similarly between groups (see Table 1). Cr-PWV decreased after NTG (both groups p &lt; 0.001) while rd-PWV increased in controls (from 4.62 ± 1.49 m/s to 5.94 ± 2.29 m/s, p &lt; 0.001) and in CKD (from 3.71 ± 1.60 m/s to 5.18 ± 2.12 m/s, p &lt; 0.001), in a similar extent (p = 0.111 for interaction term). Cd-PWV significantly increased post-NTG only in the CKD group (p = 0.009). Conclusions: Again, we observed opposing changes in the regional stiffnesses of two distinct vascular territories following the administration of a vasodilator. Here, the two segments were mid-size and small conduit muscular arteries. This technique, adapted by our team for short peripheral arterial segments, may broaden our understanding of the consequences of the inversion of the stiffness gradient.

Modifikovana milohioidna anestezija sa 4% artikainom I adrenalinom I deksametazonom u hirurgiji mandibularnih molara - pilot studija

Introduction: Mylohyoid mandibular anesthesia is not a standard and independent primary anesthesia for performing surgery on mandibular teeth. Objective: The objective was to examine the success of achieved mylohyoid anesthesia for mandibular molar surgery, by injecting an anesthetic that could penetrate the bone in the lingual region of the mandible, using the technique for modified mylohyoid mandibular anesthesia. Materials and methods: In the pilot study, 10 patients were divided into 2 equal groups (of 5 patients each), of both sexes and aged 18-75, who required mandibular anesthesia owing to mandibular molar surgery. In group I, 3.5 ml of 4% articaine with 1:100000 adrenaline, and the addition of 0.5 ml/4 mg of dexamethasone, was injected into the sublingual region of the corner of the mandible using a modified mylohyoid approach; in group II, 4 ml of 2% lidocaine with 1:100000 adrenaline was injected into the region of the mandibular foramen using the approach for standard mandibular conduction direct anesthesia. A visual analogue scale (VAS) was used for the subjective assessment of the pain during surgery in patients, the recorded duration of the realized mandibular anesthesia, as well as the total effectiveness of the achieved anesthesia, expressed in percentages. Results: A successful intervention was achieved in all patients, with different VAS scores, but within the values indicating successful anesthesia (group I: 17.40±11.10mm; group II: 12.80±4.55mm). A longer duration of anesthesia was achieved in the first group-205.2 min (3h 25 min), compared to the second group-182 min (3h 2 min). Conclusion: Mylohyoid mandibular anesthesia with 4% articaine and with adrenaline and dexamethasone could be applied as primary anesthesia for the purpose of successfully achieving standard mandibular anesthesia.

Epidermoid cyst in submandibular region: a case report

The epidermoid cyst (EC) is a rare benign tumor that can develop in any region of the human body. About 7% of these cysts are located in head and neck. They are not frequent entities in cranio-facial region and in still more rare in oral cavity 1% statistically. Almost all of them occur in sublingual region, but there are rare case reports of occurrence in other sites. The epidermoid cysts is defined by a lined stratified squamous epithelium supported by an outer layer of collagenous-rich connective tissue. The detachment of keratin from the epithelial lining criates a soft white material rich in cholesterol crystals. This lipid rich content of the cyst may produce a vigorous inflammatory reaction if cyst rupture ocurrs. We report a case of epidermoid cyst (EC) located in submandibular region and the surgical removal procedure. This study was approuved by the Ferraz de Vasconcelos Regional Hospital (IRB) and the patient signed the Informed Consensus Files additionally. Clinical and radiographic examination revealed a movable swelling but hardened on palpation procedure. Histologic analisys of the excisional biopsy confirmed the initial hypotheses that it was an EC lesion. In spite of the EC being a rare benign lesion a differential diagnose is mandatory and it should not be underestimated due to its low but possible neoplasic transformation.

Giant Epidermal Cyst of Floor of Mouth: Case Report.

Introduction: The epidermoid cysts of the mouth are located on the mid line of the floor of mouth, most likely caused by the retention of the germinal epithelium during the growth of the mandible and hyoid branchial arches. Here, we present a case of large epidermoid cyst involving sublingual region.

Comparative Evaluation of Different Brands of Nitroglycerine Controlled Release Tablets Available in Indian Market

The nitroglycerine oral solid preparations are available in the international and Indian market as – Sublingual tablets and Controlled Release tablets since a very long time. However, the quality issues (like few of the mentioned below) are consistently there. Due to this poor stability issues, even the Pharmacopoeial monographs insists on wider Dosage content uniformity limits (75 – 135% of label claim) and relaxed assay limits (90 – 115% of label claim). In the present study a comparison for the most critical quality parameters such as, Dissolution and Related substance among the In-House developed product and different brands of 2.6 mg Nitroglycerin Controlled Release tablet available in Market was carried out. It was observed that Impurity 1 MNG was not observed in any of the market product while Impurity 2 MNG was observed initially in two branded products but on stability this impurity observed in all branded products except In-house developed product. Initially, drug dissolution result of In-house developed product was comparable with the all branded product. On stability, Drug release profile of all branded product varies to a significant level from its initial value while the drug release profile of the In-house developed product remain unchanged.

Polymeric Biomaterials for Topical Drug Delivery in the Oral Cavity: Advances on Devices and Manufacturing Technologies.

There are several routes of drug administration, and each one has advantages and limitations. In the case of the topical application in the oral cavity, comprising the buccal, sublingual, palatal, and gingival regions, the advantage is that it is painless, non-invasive, allows easy application of the formulation, and it is capable of avoiding the need of drug swallowing by the patient, a matter of relevance for children and the elderly. Another advantage is the high permeability of the oral mucosa, which may deliver very high amounts of medication rapidly to the bloodstream without significant damage to the stomach. This route also allows the local treatment of lesions that affect the oral cavity, as an alternative to systemic approaches involving injection-based methods and oral medications that require drug swallowing. Thus, this drug delivery route has been arousing great interest in the pharmaceutical industry. This review aims to condense information on the types of biomaterials and polymers used for this functionality, as well as on production methods and market perspectives of this topical drug delivery route.