Ganirelix, a drug used in in vitro fertilization (IVF), prevents ovulation in women who are not ready to have children by inhibiting a gene that produces gonadotropin. Peptides are macromolecules that are able to preserve a predetermined shape while carrying out the structural and regulatory roles for which they were originally intended. Peptide structures can be altered in the production and storage processes. Therapeutic peptides' biological activity can be drastically altered by even small modifications in their primary and secondary structures. The molecules' secondary structures can be monitored by subjecting them to different processing or storage conditions. In our investigation, we used circular dichroism (CD) spectroscopy with two different software programs for secondary structure evaluation to look at how environmental factors like temperature and humidity affected the secondary structure of Ganirelix in an injectable formulation. The CD results revealed that the alpha-helical (regular and distorted), beta-sheet, beta-strands (regular and distorted), beta-turn, and random coil structures of temperature and humidity stressed generic drug products are comparable to reference-listed drug.

Stress study of a drug substance or pharmaceutical drug product provides a vision into degradation pathways and degradation products of the active pharmaceutical ingredient and helps in interpretation of the chemical structure of the degradation impurities. In the current study, Ganirelix active ingredient presented in the Orgalutran® was stressed with acidic and alkali hydrolysis, photolysis, thermal and oxidation conditions as per the guidelines of International Conference on Harmonization (ICH) Q1A (R2). Ganirelix was found to be labile under thermal and alkali hydrolytic stress conditions, while it was stable to acid hydrolytic, oxidative and photolytic stress. All degradation products were separated with a resolution > 1.5 on a C18 column (2.6 µm, 25 cm×4.6 mm) using a hydrophilic ion pair such as sodium perchlorate, at a concentration <0.04 M. In total, four major degradant impurities were found during stress study. These impurities were fractionated and desalted by flash chromatography for identification of chemical structures. LC-MS-QTOF analysis revealed that two degradation products are diastereomers of Ganirelix, one degradation product is a deamination compound and other degradation product result from the insertion of a new amino acid residue in the Ganirelix peptide sequence. The developed method is sensitive enough to quantify the related substances of Ganirelix at the 0.04% level with that of Ganirelix test concentration.

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Clobeatsol propionate foam is a topical class 1 corticosteroid used to treat itching and inflammatory arthritis on the skin occurred by allergic reactions, psoriasis and eczema. In the pharmaceutical aerosol products, Dehydrated alcohol (Ethanol) is the primary ingredient and its concentration level in the formulation composition plays a significant role in the regulation of aerosol rate, droplet shape and particle size. It can also act as solubilizer for active pharmaceutical ingredient, topical disinfectant and skin permeation enhancer. Hence accurate assay of Ethanol is a crucial quality control component. A simple and rapid gas chromatography method was developed to quantify Ethanol content in Clobetasol propionate foam drug product using fused silica glass tube non-polar capillary column (HP-5, 30 m, 0.53 mm, 1.5 µm). Ethanol in the sample was diluted with methanol after adding suitable amount of internal standard, the isopropyl alcohol solution.The developed method is precise, linear and accurate in the range of 5 mg/mL to 15 mg/mL of nominal concentration of ethanol i.e. 10 mg/mL . The presented method has an advantage of a very quick gas chromatographic separation (less than 16 min) and therefore is highly suitable for in-process and stability analysis of Ethanol content in Clobetasol propionate foam drug product.

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