Bulk stability studies

Dwivedi et al. used a thin-layer chromatographic densitometric and ultraviolet spectrophotometric methods for the simultaneous determination of primaquine and a new antimalarial agent, CDRI compound number 80/53 [68]. The new antimalari-al agent, compound 80/53 is unstable in acidic conditions where it is converted into primaquine. To conduct stability studies of this compound, thin-layer chromatography densitometric and ultraviolet spectrophotometric determination methods were developed. These methods are also suitable of the determination of compound 80/53 or primaquine in bulk and pharmaceutical dosage forms. 

GMP bulk drug synthesis, including stability studies... 

The application (or Type II DMF) should include a detailed description of the complete container closure system for the bulk drug substance as well as a description of the specific container, closure, all liners, inner seal, and desiccant (if any), and a description of the composition of each component. A reference to the appropriate indirect food additive regulation is typically considered sufficient to establish the safety of the materials of construction. The tests, methods, and criteria for the acceptance and release of each packaging component should be provided. Stability studies to establish a retest period for bulk drug substance in the proposed container closure system should be conducted with fillers or desiccant packs in place (if used). Smaller versions that simulate the actual container closure system may be used. 

A container closure system for the transportation of bulk drug products to contract packagers should be described in the application. The container closure system should be adequate to protect the dosage form, be constructed with materials that are compatible with product being stored, and be safe for the intended use. The protective properties of the shipping container are verified by the practice of including annual batches of the packaged product in postapproval stability studies. 

Compared to genosensors based on GEC, the novelty of this approach is in part attributed to the simplicity of its design, combining the hybridization and the immobilization of DNA in one analytical step. The optimum time for the one-step immobilization/hybridization procedure was found to be 60 min [66]. The proposed DNA biosensor design has proven to be successful in using a simple bulk modification step, hence, overcoming the complicated pre-treatment steps associated with other DNA biosensor designs. Additionally, the use of a one-step immobilization and hybridization procedure reduces the experimental time. Stability studies conducted demonstrate the capability of the same electrode to be used for a 12-week period [66]. 

P. C. Dabas, H. Erguven, M. C. Vescina, and C. N. Carducci, Stability study of ethyl loflazepate in bulk drug, solution and dosage form by LC, J. Pharm. Biomed. Anal., 70 241 (1992). 

For the first set of materials, and with the aim of assessing the dispatch conditions, a short-term stability study was conducted at 40°C. The layout chosen for the stability study was the so-called isochronous scheme samples were taken from the bulk, placed at 40° C and then moved back to the reference temperature (4°C), after 1 and 2 weeks. Then, at the same time, the samples were analysed for major components and trace elements. The results, 3 time-points (0, 1, 2 weeks) and 2 units analysed per time-point, were evaluated by one-way analysis of variance ANOVA. As some parameters (especially As, Cd, Cu, and to a minor extent also Mn, pH) showed a statistically significant slope of the regression line, it was decided to assure the dispatch of the samples at 4°C (with cooling elements). 

Other suggestions include the following conditions for evaluation in stability studies of solutions or suspensions of a bulk drug substance ... 

Table 10.16 summarizes some applications of HPLC in Pharmaceutical Chemistry which encompass drug stability studies, the determination of trace impurities or decomposition products in bulk drug samples, and the assay of drugs and metabolites in body fluids. 

A program for stability assessment may include storage at accelerated, long-term, and, if applicable, intermediate stability study storage conditions (refer to IV.G of the ICH Q1A Guidance and Section II.A). Stability samples should be stored in the bulk storage container equivalent (e.g., same composition and type of container, closure, and liner, but smaller in size). 

Stability studies must be conducted to support storage of product between production and packaging. This type of study should be completed before commercialization. Typically, these studies are less than 1 year and conducted at controlled room temperature. Products are stored in a simulated package such as double polyethylene bag in small fiber drum, or in plastic containers mimicking the packaging of the bulk product. Critical testing should be done every 3 months. 

Studies must be conducted to provide data to support bulk holding times for in-process or intermediate materials. For a stable drug product, it is generally acceptable that no formal study is needed if in-process materials are held less than 30 days. For unstable products or materials that need to be held longer than 30 days, stability studies are necessary to verify the holding times do not affect the quality of the in-process materials. 

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