Development of Calcitonin Salmon Nasal Spray: Similarity of Peptide Formulated in Chlorobutanol Compared to Benzalkonium Chloride as Preservative

Costantino, Henry R.; Culley, Heather; Chen, Lishan; Morris, Daniel L.; Houston, Michael E.; Roth, Sharin E.; Phoenix, Mary Jo; Foerder, Chuck; Philo, John S.; Arakawa, Tsutomu; Eidenschink, Lisa A.; Andersen, Niels H.; Brandt, Gordon; Quay, Steven C.

doi:10.1002/jps.21690

Cited by 12 publications

(5 citation statements)

References 31 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Formula Weight: Hemihydrate: 186.47, Anhydrous: 177.46. The preferred formulation described here is comprised of 0.25% weight/weight of chlorobutanol, 0.85% sodium chloride, and 98.86% purified water, and the pH is ~3.5–4.0 http://www.faqs.org/patents/app/20110009321 39 .…”

Section: Methodsmentioning

confidence: 99%

The autism/neuroprotection-linked ADNP/NAP regulate the excitatory glutamatergic synapse

et al. 2019

View full text Add to dashboard Cite

Activity-dependent neuroprotective protein (ADNP), essential for brain formation, was discovered as a leading de novo mutated gene causing the autism-like ADNP syndrome. This syndrome is phenotypically characterized by global developmental delays, intellectual disabilities, speech impediments, and motor dysfunctions. The Adnp haploinsufficient mouse mimics the human ADNP syndrome in terms of synapse density and gene expression patterns, as well as in developmental, motor, and cognitive abilities. Peripheral ADNP was also discovered as a biomarker for Alzheimer’s disease and schizophrenia, with nasal administration of the ADNP snippet peptide NAP (enhancing endogenous ADNP activity) leading to partial cognitive and functional protection at the cellular, animal and clinical settings. Here, a novel formulation for effective delivery of NAP is provided with superior brain penetration capabilities. Also provided are methods for treating pertinent clinical implications such as autism, cognitive impairments, olfactory deficits, and muscle strength using the formulation in the Adnp haploinsufficient mouse. Results showed a dramatically specific increase in brain/body bioavailability with the new formulation, without breaching the blood brain barrier. Additional findings included improvements using daily intranasal treatments with NAP, at the behavioral and brain structural levels, diffusion tensor imaging (DTI), translatable to clinical practice. Significant effects on hippocampal and cerebral cortical expression of the presynaptic Slc17a7 gene encoding vesicular excitatory glutamate transporter 1 (VGLUT1) were observed at the RNA and immunohistochemical levels, explaining the DTI results. These findings tie for the first time a reduction in presynaptic glutamatergic synapses with the autism/Alzheimer’s/schizophrenia-linked ADNP deficiency coupled with amelioration by NAP (CP201).

show abstract

Section: Methodsmentioning

confidence: 99%

The autism/neuroprotection-linked ADNP/NAP regulate the excitatory glutamatergic synapse

et al. 2019

View full text Add to dashboard Cite

show abstract

“…3. The predominant contribution of sCT is to be expected from the Tyr 22 (20). The solvent-subtracted near-UV spectra of the samples were comparable to each other and to the unprocessed sCT.…”

Section: Structural Stabilitymentioning

confidence: 66%

The effect of excipients on the stability and aerosol performance of salmon calcitonin dry powder inhalers prepared via the spray freeze drying process

et al. 2016

View full text Add to dashboard Cite

The effect of excipients on the stability and aerosol performance of salmon calcitonin dry powder inhalers prepared via the spray freeze drying processSpray freeze drying was developed to produce dry powders suitable for applications such as inhalation delivery. In the current study, the spray freeze drying technique was employed to produce inhalable salmon calcitonin microparticles. Effects of the carrier type, concentration of hydroxyl propyl-β-cyclodextrin and the presence of Tween 80 on the chemical and structural stability, as well as on the aerosol performance of the particles were investigated. The results indicated that hydroxyl propyl-β-cyclodextrin had the most important effect on the chemical stability of the powder and strongly increased its stability by increasing its concentration in the formulation. Chemically stable formulations (over 90 % recovery) were selected for further examinations. Fluorescence spectroscopy and circular dichroism suggested that the formulations were structurally stable. Aerosol performance showed that the Tween-free powders produced higher fine particle fraction values than the formulations containing Tween (53.7 vs. 41.92 % for trehalose content and 52.85 vs. 43.06 % for maltose content).Keywords: salmon calcitonin, inhalation, spray freeze drying, hydroxypropyl-β-cyclodextrin, fine particle fraction, stabilitySalmon calcitonin (sCT) is a 32-amino acid linear polypeptide hormone with a 1-7 disulfide bridge (1). It has been approved for the treatment of osteoporosis and Paget's disease; its injectable solution (Calcimar, Miacalcin) and nasal spray (Fortical, Miacalcin) are commercially available for this purpose. Parenteral delivery is an inconvenient route, especially for drugs such as sCT that have short half-lives after administration (15-20 min) and require frequent injections to retain a pharmacological effect. The nasal form shows 3 to 5 % efficacy over the parenteral dosage form (2).Pulmonary delivery of peptides and proteins is a noninvasive alternative method (3) and a promising route because the lung has an enormous absorptive surface area, very NARGES POURSINA ALIREZA VATANARA* MOHAMMAD REZA ROUINI KAMBIZ GILANI ABDOLHOSSEIN ROUHOLAMINI NAJAFABADI

show abstract

“…Funded by a generic manufacturer, this was an in vitro study testing various physicochemical properties [21]. It found identical molecular weights, amino acid compositions, and similar secondary structures, Results specific to US generic version not provided demonstrating that the difference in the preservative between the generic and brand-name versions seemed to have little effect on the molecular structure.…”

Section: Studies Of Us Fda-approved Generic Versionsmentioning

confidence: 99%

Modified Regulatory Pathways to Approve Generic Drugs in the US and a Systematic Review of Their Outcomes

Kesselheim

Fulchino

Isaman

et al. 2015

Drugs

View full text Add to dashboard Cite

Pharmaceutical manufacturers sometimes raise scientific concerns related to potential generic versions of their drugs; however, in the six cases we reviewed, these companies did not follow up the pre-approval concerns they raised with any methodologically rigorous post-approval testing using clinical endpoints. Despite their pre-approval controversy, experience with these generic drugs provides reassurance of their clinical interchangeability. Systematized post-approval study of certain generic drug bioequivalence determinations is needed.

show abstract

Development of Calcitonin Salmon Nasal Spray: Similarity of Peptide Formulated in Chlorobutanol Compared to Benzalkonium Chloride as Preservative

Cited by 12 publications

References 31 publications

The autism/neuroprotection-linked ADNP/NAP regulate the excitatory glutamatergic synapse

The autism/neuroprotection-linked ADNP/NAP regulate the excitatory glutamatergic synapse

The effect of excipients on the stability and aerosol performance of salmon calcitonin dry powder inhalers prepared via the spray freeze drying process

Modified Regulatory Pathways to Approve Generic Drugs in the US and a Systematic Review of Their Outcomes

Contact Info

Product

Resources

About