P.V

An isocratic, reversed phase-HPLC method was developed and validated for the quantitative determination of Ofloxacin and Ketorolac Tromethamine in combined-dosage form. A thermo hypersil BDS C18 (250mmx4.6mm, particle size 5µm) column with mobile phase containing water (pH - 2.8 adjusted with ortho phosphoric acid) and methanol in the ratio of 60: 40, v/v was used. The flow rate was 1.0 mL/min, column temperature was 30°C and effluents were monitored at 241 nm. The retention times of ofloxacin and ketorolac tromethamine were 4.671min and 5.751 min respectively. The correlation co-efficient values for both the ofloxacin and Ketorolac tromethamine were found to be 1. The proposed method was validated with respect to linearity, accuracy, precision, specificity, and robustness. Recovery of ofloxacin and Ketorolac tromethamine in formulations was found to be 100% confirms the non-interferences of the excipients in the formulation. Due to its simplicity, rapidness and high precision, the method can be successfully applied to the estimation of Ofloxacin and Ketorolac tromethamine in combined dosage form.

Acid-related disorders, including gastro esophageal reflux disease (GERD), duodenal ulcers, and gastric ulcers, are managed by H2 receptor antagonists and proton pump inhibitors (PPIs). PPIs represent first choice for treating acid-peptic ulcers inhibits the gastric- H+/ K+ -ATPase through covalent binding to cysteine residues of the proton pump. Achlorhydria and acute renal failure are the most common drawbacks. A reversible acid pump antagonist (APAs), currently in clinical trial removes these problems. The APAs are the conceivable future drugs for the treatment of acid-peptic disorders.

The objective of this paper is to give insight and better understanding of the regulatory requirements for changes done for an approved New Drug Application (NDA) in United States (US). For technical advancements, there may be situations which demand/ necessitate modifications for an approved NDA. The changes must be in conformance with the regulatory requirements of the Food and Drug Administration (FDA), the ultimate authority for the Drug related approvals in US. The changes must be systematically reported to the regulatory authorities in the recommended formats, termed as “Post approval changes for an NDA”. Section 506A of Federal Food, Drug, and Cosmetic Act, provides requirements for making and reporting manufacturing changes to an approved application and for distributing a drug product made with such changes. The FDA has revised its regulations on supplements and other changes to an approved application (21 CFR 314.70) to conform to section 506A of the Act. The changes can be major, moderate or minor depending on the changes likely to affect the quality, safety and efficacy of the product. Irrespective of the category of the changes, every change is to be brought to the notice of the US FDA in stringent, structured and stipulated format that are recommended for the regulatory advancements. If manufacturers are to achieve the much-heralded desired state, it is essential to allow some manufacturing changes. Firms would still be responsible for ensuring product quality. The goal is well known, the components needing change are well understood and characterized and the process well defined. Key words: NDA, USFDA, Post approval changes, Regulatory Authorities