Drug Database
ZY

Zydis (Zydis / FDDF)

✓ Approved

Cardinal Health, Inc. · therapeutic agent

What is Zydis?

Zydis is a therapeutic agent developed by Cardinal Health, Inc.. It is approved for therapeutic indications via oral (po) or sublingual (sl)/oral transmucosal.

Drug Profile

Brand NamesZydis, FDDF
CompanyCardinal Health, Inc.
RouteOral (PO), Sublingual (SL)/Oral Transmucosal
StatusApproved
Sources: ClinicalTrials.gov, Cardinal Health, Inc.

Therapeutic Indications

Zydis is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Surgical and medical proceduresOral appliance application✓ Approved

Related Research Articles

PubMedPharmaceutics2026-05-27

Emerging Perspectives in the Formulation of Lyophilized Orally Disintegrating Tablets: From Lyoc to Self-Nanoemulsifying Lyophilized Tablets (SNELTs) and Beyond into Hybrid Platforms.

Popa Eliza Grațiela EG, Mititelu Tartau Liliana L, Panainte Alina Diana AD, Păduraru Larisa L et al.

Four decades have elapsed since orally disintegrating tablets (ODTs) were first formulated as the emulsion/type Lyoc tablet, a porous mass intended to rapidly disperse in saliva. Following the lyophilization process, new formulations of ODTs were designed, intending to make a simpler and more reproducible formulationZydis, LBL-Flash, Quicksolv, and, more recently, Zydis Ultra. Lyophilization is widely recognized as an effective technique for the development of ODTs, due to its ability to produce highly porous structures that enable rapid disintegration and improved patient compliance. However, its advantages should be considered in relation to other manufacturing methods, as each technology presents specific trade-offs in terms of cost, scalability, mechanical strength, drug loading capacity, and process robustness. In line with the modern sustainable and green pharmacy trend, new raw materials have gained attention as excipients for lyophilized ODTs; these materials include certain plant derivatives, but also performant excipients with newly discovered functionalities. At present, a new generation of ODTs is available in the form of Self-Nanoemulsifying Lyophilized Tablets (SNELTs), which bring the advantages of Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) into ODTs via the lyophilization method. The technique is mostly applicable to low-solubility drugs formulated as nanoemulsions, which are absorbed onto solid carriers and further lyophilized, forming the final ODT. Despite its limitations (expensive, time-consuming, and high product friability), lyophilization is being continuously developed nowadays, in combination with other techniques (3D printing, mucoadhesion, or electrospinning), building hybrid platforms for the modern ODTs of the future.

PMID 42198308
Read full article →
PubMedCNS spectrums2023-04-01

Hyperammonemia and First-Degree Atrio-Ventricular Block in Adult Male from Valproic Acid Toxicity.

Wilson Nicholas N

The purpose of this case study is to review the clinical presentation and medical work of an adult male who experienced symptomatic hyperammonemia and first-degree atrio-ventricular block in the setting of valproic acid toxicity. This case involves a 28-year-old African American male with a past psychiatric history of bipolar 1 disorder with psychotic features, antisocial personality disorder, PTSD, and ASD, who was psychiatrically hospitalized for mania and psychosis at a large midwestern university hospital. At the time of evaluation in the emergency department, the patient endorsed suicidal ideation, religious/persecutory delusions, and auditory hallucinations of demons. Zyprexa Zydis was started and titrated to 20 mg every 12 hours, which did not sufficiently improve symptoms. Depakote EC/DR 1000 mg every 12 hours was then added for treatment of mania. Approximately 1 week later, the patient was observed to be somnolent and complained of malaise, nausea, and vomiting. Labs were collected which showed an elevated ammonia level of 336 umol/L and free valproic acid level of 13.3 mcg/ml. An EKG was performed which showed first-degree atrio-ventricular block with fusion complexes. The patient's baseline EKG displayed sinus bradycardia with no evidence of atrio-ventricular block. The patient's CMP was unremarkable except total bilirubin of 1.5 mg/dL and glucose of 104 mg/dL. His lactate was elevated at 1.95 mmol/L. The patient's troponin and CRP were unremarkable. The patient was medically transferred for management of hyperammonemia and EKG changes. Depakote was discontinued and lactulose 20 g TID was initiated. Patient was placed on telemetry and the first-degree atrio-ventricular block resolved within 24 hours after discontinuation of Depakote. Daily ammonia level, chem 7, and magnesium were collected. Ammonia decreased to 79 and 59 umol/L on consecutive days. Sodium was mildly elevated at 144 on day 2 of medical admission. Poison control was contacted and L-carnitine 990 TID was started for suspected carnitine deficiency. The patient medically recovered after several days and was readmitted to the psychiatric hospital for further psychiatric management. The patient's presentation of hyperammonemia and first-degree atrio-ventricular block were likely due to valproic acid toxicity. We suspect that carnitine deficiency contributed to the patient's valproic acid toxicity at lower-than-expected blood levels. Although antipsychotics can cause prolonged QTc interval, conduction disorders are not typical abnormalities. Caution should be taken when prescribing Depakote to individuals at higher risk of developing toxicity, including those with potential nutritional deficiencies as well as those with limited self-advocacy abilities secondary to psychiatric illness. Rapid identification of side effects, such as valproic acid toxicity, remain crucial for favorable patient outcomes. No Funding.

PMID 43010290
Read full article →
PubMedCurrent therapeutic research, clinical and experimental2022-07-12

Allergen Release Profiles of Fast-Dissolving Freeze-Dried Orodispersible Sublingual Allergy Immunotherapy Tablets.

Yamamoto Takashi T, Ohashi-Doi Katsuyo K, Matsuhara Hiroki H, Verhoog Loes L et al.

Sublingual allergy immunotherapy tablets (SLIT-tablets) provide a well-tolerated and clinically efficacious treatment for allergic disease such as allergic rhinitis and allergic asthma. In SLIT, uptake of allergen by immune-competent cells in the oral mucosa activates the immune system and leads to tolerance toward the sensitizing allergen. The ability to deliver the full allergen content into solution within the recommended sublingual holding time is therefore an essential quality of SLIT-tablets that must be supported by the tablet formulation for all relevant allergen sources. SLIT-tablets based on a fast-dissolving orodispersible freeze-dried formulation (Zydis) are currently available for 5 of the most prevalent allergens: tree (birch and related species from the birch-homologous group), grass, ragweed, Japanese cedar, and house dust mite. The purpose of this study was to examine the allergen release properties of three freeze-dried SLIT-tablets containing tree, ragweed, and Japanese cedar extracts, respectively. The correlation between SLIT-tablet allergen release and the level of allergen-specific T-cell activation was examined for the tree SLIT-tablet. Allergen release kinetics and tablet disintegration times for the 3 freeze-dried SLIT-tablets were examined. For all 3 tablets, the magnitude of solubilized major allergen relative to time in solution was compared to external controls to achieve a measure of the total allergen release. Additional assessments of allergen release occurring after the initial timepoint (15 or 30 seconds in solution) were done independently of external controls by linear regression analyses. For the tree SLIT-tablet, the immunological potency of the released major allergen was assessed at each experimental timepoint by a Bet v-specific T-cell activation assay. All 3 SLIT-tablets disintegrated within 1 second after contact with assay buffer without any detectible residue. Complete release of major allergens (Bet v 1, Amb a 1, and Cry j 1, respectively) was seen at the earliest experimental time points (15 or 30 seconds). For the tree SLIT-tablet, full T-cell activation was achieved at 30 seconds (earliest experimental time point). The freeze-dried SLIT-tablet formulation consistently provides rapid and complete release of allergen from a wide range of species in a standardized in vitro assay. Full release of the SLIT-tablet allergen content within the sublingual holding time is a prerequisite for maximal exposure of allergens to the sublingual mucosa immune system. The freeze-dried SLIT-tablet formulation examined here supports short sublingual holding times and furthermore offers a convenient administration form of allergy immunotherapy.

PMID 35813554
Read full article →
PubMedClinical and molecular allergy : CMA2020-06-17

New perspectives in allergen specific immunotherapy driven by big trials with house dust mite sublingual SQ® tablets.

Vitiello Gianfranco G, Maltagliati Lucia L, Rossi Oliviero O

House-dust mites (HDM) allergy is the prevailing condition in subjects allergic to inhalants. Clinical studies with HDM extracts-either subcutaneous (SCIT) or sublingual (SLIT) have long been characterized by small sample size, varying allergen doses, and poorly defined endpoints assessing disease severity. In the last decade, well-designed, randomized, controlled studies recruiting thousands of patients have been conducted with newly developed HDM sublingual tablets (SQ®-HDM tablets). This drug is easily dispersible in the oral cavity due to the patented Zydis® technology and its allergen composition is balanced in terms of group I and group II major mite allergen content, reflecting the equal contribution of the two components to HDM sensitization. HDM is the most common allergen associated with asthma. Clinical efficacy of the SQ® HDM SLIT-tablet in HDM allergic asthma has been evaluated in randomized, double-blind, placebo-controlled trials. Both endpoints related to "present" asthma control (inhaled corticosteroid-ICS) as well as endpoints related to "future" asthma control (occurrence of asthma exacerbations) were included in these studies, in agreement with GINA (Global Initiative for Asthma) guidelines. Based on the positive results of these studies, SQ®-HDM SLIT-tablets were approved Europe-wide as registered drug for treating moderate-to-severe allergic rhinitis with or without allergic asthma and not well controlled HDM allergic asthma, associated with allergic rhinitis of any severity. GINA guidelines in 2017 included SLIT-tablet-based immunotherapy as an "add-on" treatment for asthmatic patients sensitized to HDM; indeed, allergen immunotherapy (AIT) is considered to be a complementary treatment option that targets the immunological of allergic diseases, representing the only treatment potentially disease-modifier or, at least, with a long-term efficacy. The availability of a safe, standardized, registered treatment for HDM respiratory allergies is pivotal in the immunotherapy field, pushing it out of a century-long limbo of amatorial interest towards the full dignity deserved by the only casual treatment of respiratory allergies.

PMID 32536827
Read full article →
PubMedToxicological sciences : an official journal of the Society of Toxicology2020-02-11

Assessing Effects of BHV-0223 40 mg Zydis Sublingual Formulation and Riluzole 50 mg Oral Tablet on Liver Function Test Parameters Utilizing DILIsym.

Longo Diane M DM, Shoda Lisl K M LKM, Howell Brett A BA, Coric Vladimir V et al.

For patients with amyotrophic lateral sclerosis who take oral riluzole tablets, approximately 50% experience alanine transaminase (ALT) levels above upper limit of normal (ULN), 8% above 3× ULN, and 2% above 5× ULN. BHV-0223 is a novel 40 mg rapidly sublingually disintegrating (Zydis) formulation of riluzole, bioequivalent to conventional riluzole 50 mg oral tablets, that averts the need for swallowing tablets and mitigates first-pass hepatic metabolism, thereby potentially reducing risk of liver toxicity. DILIsym is a validated multiscale computational model that supports evaluation of liver toxicity risks. DILIsym was used to compare the hepatotoxicity potential of oral riluzole tablets (50 mg BID) versus BHV-0223 (40 mg BID) by integrating clinical data and in vitro toxicity data. In a simulated population (SimPops), ALT levels > 3× ULN were predicted in 3.9% (11/285) versus 1.4% (4/285) of individuals with oral riluzole tablets and sublingual BHV-0223, respectively. This represents a relative risk reduction of 64% associated with BHV-0223 versus conventional riluzole tablets. Mechanistic investigations revealed that oxidative stress was responsible for the predicted ALT elevations. The validity of the DILIsym representation of riluzole and assumptions is supported by its ability to predict rates of ALT elevations for riluzole oral tablets comparable with that observed in clinical data. Combining a mechanistic, quantitative representation of hepatotoxicity with interindividual variability in both susceptibility and liver exposure suggests that sublingual BHV-0223 confers diminished rates of liver toxicity compared with oral tablets of riluzole, consistent with having a lower overall dose of riluzole and bypassing first-pass liver metabolism.

PMID 32040174
Read full article →
PubMedClinical pharmacology in drug development2019-10-15

A Pharmacokinetic Bioequivalence Study Comparing Sublingual Riluzole (BHV-0223) and Oral Tablet Formulation of Riluzole in Healthy Volunteers.

Qureshi Irfan I, Lovegren Meghan M, Wirtz Victoria V, Larouche Richard R et al.

Orally administered riluzole extends survival in patients with amyotrophic lateral sclerosis, although it has significant shortcomings (eg, adverse events, dysphagic patients) that limit its utility. BHV-0223 is a Zydis-based orally disintegrating formulation of riluzole designed for sublingual administration that addresses the limitations of conventional tablets. This study assessed the bioequivalence between 40-mg BHV-0223 and standard 50-mg oral riluzole tablets, and the food effect on BHV-0223 pharmacokinetics in healthy volunteers. Overall, 133 healthy subjects received BHV-0223 and riluzole tablets under fasted conditions. Geometric mean ratios for the area under the plasma concentration-time curve (AUC) from time zero to time of last nonzero concentration (AUC0-t ) (89.9%; confidence interval [CI], 87.3%-92.5%), AUC from time zero to infinity (AUC0-∞ ) (89.8%; CI, 87.3%-92.4%), and maximum observed concentration (112.7%; CI, 105.5%-120.4%) all met bioequivalence criteria (80%-125%). Subsequently, 67 subjects received BHV-0223 under fed conditions. The geometric mean ratios of AUC0-t (91.2%; CI, 88.1-94.3%), and AUC0-∞ (92.0%; CI, 89.0-95.1%) were similar, but maximum observed concentration ratios were not within bioequivalence criteria. BHV-0223 was well tolerated. This study demonstrated that 40-mg sublingual BHV-0223 is bioequivalent to 50-mg oral riluzole tablets.

PMID 31610101
Read full article →

+20 more articles available with a free account

Sign up free to view all articles →

Ask about Zydis