Study of the kinetics of benzidamine hydrochloride release from topical sprays in an in vitro experiment

Mapping Intimacies ◽

10.33920/med-13-2006-05 ◽

2020 ◽

pp. 62-72

Author(s):

E. F. Stepanova ◽

V. V. Vernikovskiy ◽

A. V. Morozov

Keyword(s):

Active Substance ◽

Dosage Form ◽

Topical Therapy ◽

Chemical Properties ◽

Vitro Experiment ◽

In Vitro Experiment ◽

Analgesic Effects ◽

Inflammatory Processes ◽

Osmotic Activity

Inflammatory processes accompanied by a sore throat are a widespread symptom of both infectious and non-infectious genesis. In this case, topical therapy with medications that combine anti-inflammatory and analgesic effects, in the form of comfortable dosage forms — sprays, is the most effective. In this case, the used drug has a complex effect on contact tissues, due to both the actual pharmacological activity of the pharmaceutical substance and the physico-chemical properties of the excipients forming the dosage form. A study of the release of the active substance from sprays in the perspective of their topical application, as well as their osmotic activity in an in vitro experiment that simulates the process of application to the throat mucosa, was carried out. The real influence of the osmotic activity of the dosage form on the degree of release of the active substance due to the multidirectional nature of the resulting diffusion flows is shown.

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In Silico and in Vitro Evaluation of Deamidation Effects on the Stability of the Fusion Toxin DAB389IL-2

Current Proteomics ◽

10.2174/1570164616666190131150033 ◽

2019 ◽

Vol 16 (4) ◽

pp. 307-313 ◽

Cited By ~ 2

Author(s):

Nasrin Zarkar ◽

Mohammad Ali Nasiri Khalili ◽

Fathollah Ahmadpour ◽

Sirus Khodadadi ◽

Mehdi Zeinoddini

Keyword(s):

In Silico ◽

Catalytic Domain ◽

Md Simulations ◽

Special Importance ◽

Native Form ◽

Vitro Experiment ◽

In Vitro Experiment ◽

Pharmaceutical Protein ◽

The Stability

Background: DAB389IL-2 (Denileukin diftitox) as an immunotoxin is a targeted pharmaceutical protein and is the first immunotoxin approved by FDA. It is used for the treatment of various kinds of cancer such as CTCL lymphoma, melanoma, and Leukemia but among all of these, treatment of CTCL has special importance. DAB389IL-2 consists of two distinct parts; the catalytic domain of Diphtheria Toxin (DT) that genetically fused to the whole IL-2. Deamidation is the most important reaction for chemical instability of proteins occurs during manufacture and storage. Deamidation of asparagine residues occurs at a higher rate than glutamine residues. The structure of proteins, temperature and pH are the most important factors that influence the rate of deamidation. Methods: Since there is not any information about deamidation of DAB389IL-2, we studied in silico deamidation by Molecular Dynamic (MD) simulations using GROMACS software. The 3D model of fusion protein DAB389IL-2 was used as a template for deamidation. Then, the stability of deamidated and native form of the drug was calculated. Results: The results of MD simulations were showed that the deamidated form of DAB389IL-2 is more unstable than the normal form. Also, deamidation was carried by incubating DAB389IL-2, 0.3 mg/ml in ammonium hydrogen carbonate for 24 h at 37o C in order to in vitro experiment. Conclusion: The results of in vitro experiment were confirmed outcomes of in silico study. In silico and in vitro experiments were demonstrated that DAB389IL-2 is unstable in deamidated form.

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