Stability Study of Finasteride: Stability-Indicating LC Method, In Silico and LC–ESI-MS Analysis of Major Degradation Product, and an In Vitro Biological Safety Study

Purpose: The feasibility of preparing an eslicarbazepine acetate suspension using Aptiom tablets for administration via enteral feeding tubes was evaluated. Methods: Eslicarbazepine acetate suspension (40 mg/mL) was prepared using Aptiom tablets after optimizing the tablet crushing methods and the vehicle composition. A stability-indicating high-performance liquid chromatography (HPLC) method was developed to monitor the eslicarbazepine stability in the prepared suspension. Three enteric feeding tubes of various composition and dimensions were evaluated for the delivery of the suspensions. The suspension was evaluated for the physical and chemical stability for 48 hours. Results: The reproducibility and consistency of particle size reduction was found to be best with standard mortar/pestle. The viscosity analysis and physical stability studies showed that ORA-Plus:water (50:50 v/v) was optimal for suspending ability and flowability of suspension through the tubes. The developed HPLC method was found to be stability indicating and suitable for the assay of eslicarbazepine acetate in the prepared suspension. The eslicarbazepine concentrations in separately prepared suspensions were within acceptable range (±3%), indicating accuracy and reproducibility of the procedure. The eslicarbazepine concentrations in suspensions before and after delivery through the enteric feeding tubes were within acceptable range (±4%), indicating absence of any physical/chemical interactions of eslicarbazepine with the tubes and a successful delivery of eslicarbazepine dosage via enteric feeding tubes. The stability study results showed that eslicarbazepine concentration in the suspension remained unchanged when stored at room temperature for 48 hours. Conclusion: The study presents a convenient procedure for the preparation of a stable suspension of eslicarbazepine acetate (40 mg/mL) using Aptiom tablets, for administration via enteral feeding tubes.

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Studying Microwave-Assisted Hydrolytic Degradation of Colchicine using RP-Chromatographic Methods: In Silico ADME/Tox Profile and Molecular Docking

10.21203/rs.2.16552/v1 ◽

2019 ◽

Author(s):

nada abdelwahab ◽

hossam mokhtar ◽

asmaa aboulmaged

Keyword(s):

Degradation Product ◽

In Silico ◽

Oral Absorption ◽

Hydrolytic Degradation ◽

High Sensitivity ◽

Flash Chromatography ◽

Stability Indicating ◽

Microwave Assisted ◽

Chromatographic Methods ◽

Validation Parameters

Abstract Colchicine, is a natural amide containing anti-gout treatment with versatile applications. Microwave assisted hydrolytic degradation is a newly alternative method thought to be more promising than traditional procedures of heating. It is an ecofriendly method that has more reproducible results due to the control of parameters. From this point, carrying on hydrolytic degradation of colchicine was tested for the first time under acidic conditions with the aided of microwave. The drug was hydrolyzed with the formation of deacylated analogue. Isolation of the resulted degradate was carried out using flash chromatography, the isolated one was elucidated based on 1 H NMR data. Moreover, the results of human pharmacokinetic predictions conducted from in silico data showed that colchicine had higher blood brain barrier (BBB), plasma protein binding, and oral absorption than its deacylated derivative. The study was also extended to forecast the binding of colchicine and its degradate to the target protein. Furthermore, two stability indicating chromatographic methods were developed for quantification of the drug and its degradation product with high sensitivity. The first method was RP-TLC densitometric method that based on using a solvent mixture of water: methanol: diethylamine (70: 30: 15, by volume). The second one was RP-HPLC at which a mixture of water (containing 0.02% diethyl amine): methanol: acetonitrile (50: 20: 30, by volume) was the used mobile phase. Validation parameters were calculated according to ICH recommendations and all were within the acceptable limits. These methods were used for determination of colchicine in its available tablets. They are the first developed stability indicating methods for analysis of colchicine and its degradation product.

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HPLC–DAD Method for Simultaneous Determination of Dipyrone (Metamizole) and Caffeine in Tablets and Identification of Major Degradation Product by Direct Infusion ESI–MS

Chromatographia ◽

10.1007/s10337-017-3263-9 ◽

2017 ◽

Vol 80 (3) ◽

pp. 489-495 ◽

Cited By ~ 2

Author(s):

James Cabral Vieira ◽

Rubia Adriele Sversut ◽

Isadora Theodoro Maciel ◽

Aline Regina Hellmann Carollo ◽

Marcos Serrou do Amaral ◽

...

Keyword(s):

Simultaneous Determination ◽

Degradation Product ◽

Direct Infusion ◽

Esi Ms ◽

Major Degradation Product

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Endophytic Fungi Penicillium species BCt Phytochemicals Inhibit Replication of Enzymes of Human Immuno-deficiency Virus 1 in in vitro and in silico Studies

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2021.14.5.6 ◽

2021 ◽

Vol 14 (5) ◽

pp. 5624-5633

Author(s):

Govindappa M ◽

Channabasava ◽

Ritu Pawar ◽

Chandrasekhar Srinivasa ◽

Chandan Shivamallu ◽

...

Keyword(s):

Amino Acids ◽

Endophytic Fungi ◽

In Silico ◽

Methanol Extract ◽

Penicillium Species ◽

Ms Analysis ◽

In Silico Studies ◽

Hiv 1

The present investigation was aimed to know the coumarins in the methanol extract of endophytic fungi, Penicillium species BCt isolated from Calophyllum tomentosum bark tissues using qualitative and GC-MS analysis. The endophytic extract was evaluated for anti-HIV activity on three replicating enzymes in vitro and in silico. The methanol extract of Penicillium species confirmed the presence of coumarins in four qualitative methods and yielded four different types of coumarins in GC-MS. In GC-MS analysis, totally seven different phytochemicals were identified based on retention time and compared with available library data. The four coumarins are coumarin (2H-1-benzopyran-2-one), coumaric acid (3-benzofuran-carboxylic acid), hynecromone (coumarin 4), 4-hydroxy-9-(3-methyl-2-butyl) furo (3,2-g) chloronen-7-one) and other three are common phytochemicals. The HIV-1 RT (98) was strongly inhibited by the endophytic fungal extract compared to integrase (118) and protease (158) in vitro analysis. Highest inhibition of integrase was observed with coumarilic acid (-17.62) when attached to Glu-35, Asn-38, Ser-39 amino acids. The protease was inhibited strongly by hymecromone (-16.39) when attached to amino acids of Val-77, Glu-34, Pro-79, Gly-78. The inhibition of RT was observed with coumarilic acid by attaching to Ala-445, Arg-567, Asp-456, Glu-478, Ser-499, Asn-474 (-23.54) significantly. Based on above results, the endophytic fungal coumarins have the ability to inhibit the three replicating enzymes of HIV-1 significantly. The in-silico results are evidence for how coumarins inhibiting the HIV replicating proteins by binding at specific amino acids. The results will help to understand how and where phytochemicals bind to target proteins to inhibit their action and it may help to identification of drugs to treat HIV. To validate our results, the in vivo research is needed.

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