Pharmaceutical products design problem

In response to the country s major public health problems, a mechanism for speeding up the approval of pharmaceutical products of certain therapeutic classes has been established. The criteria for consideration will focus on the severity of the disease and the absence of satisfactory alternative therapy which will be considered for medical risk-benefit judgment in making the final decision on the approval of new pharmaceutical products. At present, the pharmaceutical products under the fast-track scheme will cover the medicines for serious or life-threatening sicknesses such as anti-HIV, anticancer, and pharmaceutical products designated as orphan drugs which are entitled to priority review and approved by the... 

Solutions to practical problems rarely depend upon a single technique or a single approach. The following example of an impurity identification in a pharmaceutical product illustrates the key role that LC-MS can play in such an investigation, but also illustrates the limitations of the technique. The identification of this impurity has been published elsewhere in complete detail [75]. The problem and solution is summarized here. The impurity, designated as H3, was observed at 0.15% in a bulk lot of the drug substance in the structure below. The impurity required identification before the bulk lot could be released for use in further studies. 

Solvent design for crystallization of pharmaceutical products (b) Sub-problem 2 ... 

For foods and pharmaceutical products, the handling of slurries and solids at industrial scale presents problems where the product is exposed on filters and in dryers, rather than being enclosed within a pipe or vessel as a liquid. Contamination of the crystalline material can occur, and the product itself or the solvent phase it must be removed from might be toxic. Various types of equipment have therefore been developed to enable wet crystalline cakes and dry powders to be handled in a contained manner, using specially designed booths, isolators, and pack off systems to protect the product from its environment (and vice versa for highly potent materials). 

A wide range of over-the-counter and prescription pharmaceutical products use manually actuated pumps. A common example is the nasal spray container. When the design of these pumps allows contaminated products to be used, the patients and the manufacturer have a problem. This was the case, when palmitic, myristic, stearic, and oleic fatty acids (these are all non-formulation ingredients) were found in a nasal spray product. 

Spectrometric methods are usually recommended by pharmacopoeias for the assay of pharmaceutical products.55 These require both a separation step and a calibration graph. The resolution of a spectrometric method used for assay of a ternary or quaternary mixture of drugs is not good when a certain, well-known calibration graph is used. To obtain the maximum reliability for data processing it is necessary to use the PLS methodology222 because it eliminates the need for sample pretreatment. This model represents essentially an optimization method that can be applied to the problem of the experimental design. 

Special considerations are needed for the design of pharmaceutical products. As the desip team creates and assesses the primitive problem, it is important to be aware of the typical development cycle or time line for the discovery and development of a new chemical entity, as discussed thoroughly by Pisano in The Development Factory (1997). The four key steps are examined next. 

The manufacturing of hormonal products and medications to treat hormonal disorders is a significant segment of the pharmaceutical industry. Patients with chronic conditions, such as diabetes and hypothyroidism, are lifelong consumers. Many women take hormonal medications to deal with menopausal symptoms or dysmenorrhea (painful menstruation), and many use hormonal contraceptives (piUs, patches, or VE inal rings). In addition to hormonal products, many pharmaceuticals are designed to treat endocrine problems. These include medications to boost enei, aid in weight loss, induce sleep, and lower blood pressure. 

Continuous reactors in the pharmaceutical and specialty chemical industries may not only be needed for high productivity as in other segments of the chemical industry, but additionally to solve specific reactor design problems caused by limitations in batch operation. These limitations include heat transfer, mass transfer, and mixing. Continuous reactors are also used to minimize the reacting volume of thermally potent and/or noxious reactions and to decrease the potential and exposure for catastrophic failure of a vessel. Chemical industry reactor standards such as packed bed, fluid bed, and trickle bed reactors And limited utility since this type of phase contacting can usually be achieved in a slurry reactor, where residence time distribution variations, which can lead to changes in product distributions, are eliminated. Continuous stirred tank reactor operation is used only... 

The purification of value-added pharmaceuticals in the past required multiple chromatographic steps for batch purification processes. The design and optimization of these processes were often cumbersome and the operations were fundamentally complex. Individual batch processes requires optimization between chromatographic efficiency and enantioselectivity, which results in major economic ramifications. An additional problem was the extremely short time for development of the purification process. Commercial constraints demand that the time interval between non-optimized laboratory bench purification and the first process-scale production for clinical trials are kept to a minimum. Therefore, rapid process design and optimization methods based on computer aided simulation of an SMB process will assist at this stage. 

The design of crystallization processes for the manufacture of Active Pharmaceutical Ingredients is a significant technical challenge to Process Research and Development groups throughout the Pharmaceutical and related industries. It requires an understanding of both the thermodynamic and kinetic aspects of crystallization, to ensure that the physical properties of the product will consistently meet specification. Failure to address these issues may lead to production problems associated with crystal size, shape and solubility, and to dissolution and bioavailability effects in the formulated product. 

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