- Eco-Friendly Green Liquid Chromatographic Determination of Azelastine in the Presence of its Degradation Products: Applications to Degradation Kinetics. [Journal Article]
- JAJ AOAC Int 2018 Aug 10
- Background: Green solvents such as microemulsion were used in the proposed method because they play a vital role in the analytical method's influence on the environment. Objective: A highly sensiti...
Background: Green solvents such as microemulsion were used in the proposed method because they play a vital role in the analytical method's influence on the environment. Objective: A highly sensitive, specific, and validated stability-indicating eco-friendly green microemulsion liquid chromatography (MELC) method was developed for separation of the antihistaminic drug Azelastine HCl (AZL) from its degradation products with application to degradation kinetics. Methods: Chromatographic separation was operated on a C18 column with a microemulsion mobile phase, which consists of 0.1 M sodium dodecyl sulphate, 10% n-propanol, 1% n-octanol, and 0.3% triethylamine, by using 0.02 M phosphoric acid at pH 3.5 and irbesartan as internal standard. The eluted compounds were monitored at 210 nm with flow rate 1 mL/min at ambient temperature. Results: A linear dependence of the peak area on drug concentration over the concentration range of 0.1 to 25 μg/mL was achieved with an LOD of 0.04 μg/mL and an LOQ of 0.10 μg/mL. Moreover, the proposed method was successfully applied for determination of AZL in eye drops and metered dose nasal inhaler as well as to study the kinetics of alkaline, acidic, neutral, oxidative, and photolytic degradation processes of AZL according to the International Council for Harmonization guidelines. Conclusions: The proposed method could be used as a harmless alternative for quality control analysis of the mentioned drug, without interference from dosage form additives or decomposition products. Highlights: A highly sensitive stability-indicating eco-friendly green MELC method was developed for the separation of the antihistaminic drug AZL from its degradation products.
- Structure Investigation, Enrichment Analysis and Structure-based Repurposing of FDA-approved Drugs as Inhibitors of BET-BRD4. [Journal Article]
- JBJ Biomol Struct Dyn 2018 Aug 06; :1-22
- We report herein detailed structural insights into the ligand recognition modes guiding bromodomain selectivity, enrichment analysis and docking-based database screening for the identification of the...
We report herein detailed structural insights into the ligand recognition modes guiding bromodomain selectivity, enrichment analysis and docking-based database screening for the identification of the FDA-approved drugs that have potential to be the human BRD4 inhibitors. Analysis of multiple X-ray structures prevailed that the lysine-recognition sites are highly conserved, and apparently, the dynamic ZA loop guides the specific ligand-recognition. The protein-ligand interaction profiling revealed that both BRD2 and BRD4 shared hydrophobic interaction of bound ligands with PRO-98/PRO-82, PHE-99/PHE-83, LEU-108/LEU-92, and direct H-bonding with ASN-156/ASN-140 (BRD2/BRD4), while on the other hand the water-mediated H-bonding of bound ligands with PRO-82, GLN-85, PRO-86, VAL-87, ASP-88, LEU-92, TYR-97 and MET-132, and aromatic π - π stacking with TRP-81 prevailed as unique interaction in BRD4, and were not observed in BRD2. Subsequently, through ROC curve analysis, the best enrichment was found with PDB-ID 4QZS of BRD4 structures. Finally, through docking-based database screening study, we found that several drugs have better binding affinity than the control candidate lead (+)-JQ1 (Binding affinity = -7.9 kcal/mol), a well-known BRD4 inhibitor. Among the top-ranked drugs, azelastine, a selective histamine H1 receptor antagonist, showed the best binding affinity of -9.3 kcal/mol and showed interactions with several key residues of the acetyl lysine binding pocket. Azelastine may serve as a promising template for further medicinal chemistry. These insights may serve as basis for structure-based drug design, drug repurposing and the discovery of novel BRD4 inhibitors.
- Efficient UPLC and CE Methods for the Simultaneous Determination of Azelastine Hydrochloride and Its Genotoxic Impurity. [Journal Article]
- BCBiomed Chromatogr 2018 Jul 25; :e4346
- A novel Stability indicating UPLC and CE methods were established and validated for the determination of azelastine hydrochloride (AZL) and its genotoxic impurity, benzohydrazide (BHZ) in the presenc...
A novel Stability indicating UPLC and CE methods were established and validated for the determination of azelastine hydrochloride (AZL) and its genotoxic impurity, benzohydrazide (BHZ) in the presence of benzalkonium chloride (BC). The developed UPLC method was based on chromatographic separation using C18 column as a stationary phase and acetonitrile: (0.1 % w/v) aqueous sodium lauryl sulfate (55:45, v/v, pH=5 with phosphoric acid) as a mobile phase with a flow rate of 1.2 mL/min and UV detection at 215 nm. The chromatographic run time was approximately 2 min. On the other hand, the developed CE method depended on using a stationary phase of Standard Bare Fused Silica Capillaries (75 μm i.d. × 59 cm and 50 cm detection length) and the applied voltage was 30 KV using 40 mM Phosphate buffer (pH=2 with aqueous H3 PO4 ), the detection wave length was at 225 nm. Analysis time was about 6 min. The suggested methods were successfully applied for the analysis of AZL in pharmaceutical preparation. The validity of the developed methods was assessed by applying the standard addition technique and no interference from excipients was observed. The results obtained by the proposed methods were statistically analyzed and compared with the manufacturer's method and no significant difference was found between the compared methods.
- Topical antihistamines, mast cell stabilizers, and dual-action agents in ocular allergy: current trends. [Journal Article]
- COCurr Opin Allergy Clin Immunol 2018 Jul 16
- CONCLUSIONS: The topical dual-action agents are the most effective agents treating signs and symptoms of mild forms of AC. There is superiority to the high-concentration olopatadine drug over other agents on ocular itch, with prolonged effect when used once-daily.
- Drugs and Lactation Database (LactMed) [BOOK]
- BOOKNational Library of Medicine (US): Bethesda (MD)
- Small occasional doses of azelastine nasal spray would not be expected to cause any adverse effects in breastfed infants. Larger doses or more prolonged use of the nasal spray may cause drowsiness an...
Small occasional doses of azelastine nasal spray would not be expected to cause any adverse effects in breastfed infants. Larger doses or more prolonged use of the nasal spray may cause drowsiness and other effects in the infant or decrease the milk supply, particularly in combination with a sympathomimetic such as pseudoephedrine or before lactation is well established. The oral, nonsedating antihistamines are preferred alternatives. Because absorption from the eye is limited, azelastine would not be expected to cause any adverse effects in breastfed infants. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue.
- Rapid onset of action and reduced nasal hyperreactivity: new targets in allergic rhinitis management. [Review]
- CTClin Transl Allergy 2018; 8:25
- CONCLUSIONS: With the most rapid onset of action and onset of clinically-relevant effect of any AR medication currently available, and proven efficacy in the treatment of NHR, MP-AzeFlu is an AR treatment which provides what patients want, and fits how patients manage their AR in real life.
- Investigation of the spectrofluorimetric behavior of azelastine and nepafenac: Determination in ophthalmic dosage forms. [Journal Article]
- SASpectrochim Acta A Mol Biomol Spectrosc 2018 Nov 05; 204:260-266
- The first spectrofluorimetric report investigating the fluorimetric behavior of the antihistaminic drug, azelastine (AZEL), and the non-steroidal anti-inflammatory drug, nepafenac (NEP), either in bu...
The first spectrofluorimetric report investigating the fluorimetric behavior of the antihistaminic drug, azelastine (AZEL), and the non-steroidal anti-inflammatory drug, nepafenac (NEP), either in bulk or in their dosage forms, eye drops and ophthalmic suspension. After a full investigation of the factors that may influence their spectrofluorimetric behavior: pH, different organized media and organic solvents, the optimum factors were set in order to enable the analysis of each drug with maximum sensitivity. The AZEL spectrofluorimetric analysis was set at 286/364 (λex/λem) in distilled water while for NEP, the analysis was set at 228/303 (λex/λem) in methanol. The linearity range for AZEL was from 0.1 to 1.5 μg/mL while that of NEP was from 0.2 to 1.5 μg/mL. The linearity yielded good regression parameters with low LOD (0.022 and 0.032 μg/mL for AZEL and NEP, respectively) and LOQ (0.073 and 1.08 μg/mL for AZEL and NEP, respectively) when compared with those obtained from many previous spectroscopic and chromatographic reports in literature. The method was ICH validated and was applied to the analysis of AZEL and NEP with good selectivity regarding the inactive ingredients.
- Influence of MP 29-02 on ciliary beat frequency in human epithelial cells in vitro. [Journal Article]
- EAEur Arch Otorhinolaryngol 2018; 275(6):1483-1490
- CONCLUSIONS: MP 29-09 significantly reduced CB, with an almost linear relationship between the MP 29-09 concentration and reduction in CBF. For fluticasone propionate, a significant reduction of CBF was observed only at the highest analyzed concentration. The findings have implications for the long-term use of the MP 29-02. Yet, further clinical studies are needed to confirm these results in vivo, especially in patients with seasonal or perennial allergic rhinits.
- Safety of a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in children: A randomized clinical trial. [Journal Article]
- AAAllergy Asthma Proc 2018 Mar 01; 39(2):110-116
- CONCLUSIONS: The intranasal formulation of AZE and FP was safe and well tolerated after 3 months' continuous use in children with allergic rhinitis.The study was registered on <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://ClinicalTrials.gov">ClinicalTrials.gov</ext-link> (NCT01794741).
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- Onset of Action of the Fixed Combination Intranasal Azelastine-Fluticasone Propionate in an Allergen Exposure Chamber. [Journal Article]
- JAJ Allergy Clin Immunol Pract 2018 Feb 07
- CONCLUSIONS: MP-AzeFlu had a more rapid onset of action (5 minutes) and was more effective than LORA/INFP.