Pharmaceutical performance

Taylor, A., and Gustafsson, P. (2005), Do all dry powder inhalers show the same pharmaceutical performance Int. I. Clin. Pract. Suppl., 59,7-12. 

While establishing molecular networks for cocrystal design and determining crystal structures is very important, the value of cocrystals of pharmaceutical components lies in the ability to tailor the functionality of materials. In contrast to polymorphs that have the same chemical composition, cocrystals do not. As such, one would expect that with cocrystals one could introduce greater changes in material properties than with polymorphs. Properties that relate to pharmaceutical performance and that can be controlled by cocrystal formation include melting point, solubility, dissolution, chemical stability, hygroscopicity, mechanical properties, and bioavailability. The cocrystals for which pharmaceutical properties have been studied are few and some of these are presented below. Clearly further research in this area is needed. 

Some of the more common performance measurement systems used to assess pharmaceutical outcomes include report cards, balanced scorecards, clinical value compasses, profiling, performance-based evaluation systems, and others. The goals of pharmaceutical performance measurement systems are to 1) compare treatment modalities fairly 2) recognize and promote good care 3) identify and eliminate substandard care and 4) improve the level of care overall.Because performance measures can include data over the course of treatment, the outcomes of alternative therapies and practices may be detected. The end goal of any performance measurement system should not be cost containment only improving patient outcomes must be a primary concern, keeping in mind the cost effectiveness of the therapy and sustainability of the system. 

David Eddy at Duke University has written extensively on the problems and potential solutions related to pharmaceutical performance measurement systems. According to a U.S. survey, the most commonly perceived problems with pharmaceutical performance measurement systems are limitations with billing and administrative databases, lack of time to review summary data by physicians, and incomplete data. Other limitations include risk adjustment (what if my practice has sicker patients), overreliance on administrative (claims) data rather than clinical data (therefore lacking key patient outcomes), patient individuality and variation in medical practice, and lack of capacity for taking into account a discipline-specific rather than a whole programs-oriented CQI approach. There has also been some debate on the reliability of performance measurement systems to assess the true impact of physician care on the quality of health care.t ... 

Likewise, modification of either PheB 1 or LysB29 has been shown to improve the pharmaceutical performance (eg., increased plasma half-life, reduced immuno-genicity and antigenicity, improved resistance to proteolysis, increased aqueous/ organic solubilities) of the insulin conjugates thus produced while not significantly... 

Unlike the physical diameter, the is a concept incorporating the size, shape and density of particles [2] and so the pharmaceutical performance of a powder or droplets for pntmonary delivery wonld be defined by the mass median aerodynamic diameter (MM AD) of the particles. MM AD is the equivalent aerodynamic diameter in which 50% of the powder mass falls below [4]. Therefore, the MMAD is representative of the aerodynamic particle size of an aerosol formulation. An MMAD of <5 pm is desirable for deep Inng delivery. 

Historically, drug absorption, distribution, metabolism, excretion, and toxicity ADMET) studies in animal models were performed after the identification of a lead compound. In order to avoid costs, nowadays pharmaceutical companies evaluate the ADMET profiles of potential leads at an earlier stage of the development... 

Foremost we hope - and believe - that chemoinformatics will become of increasing importance in the teaching of chemistry. The instruments and methods that are used in chemistry will continue to swamp us with data and we have to manage these data to increase our chemical knowledge. We have to understand more deeply, and exploit, the results of our experiments. Concomitantly, demands on the properties of the compounds that are produced by the chemical and pharmaceutical industries will continue to rise. We will need materials that are better we need them to be more selective, have fewer undesirable properties, able to be broken down easily in the environment without producing toxic by-products, and so on. This asks for more insight into the relationships between chemical structures and their properties. Furthermore, we have to plan and perform fewer and more efficient experiments. 

Beyond pharmaceutical screening activity developed on aminothiazoles derivatives, some studies at the molecular level were performed. Thus 2-aminothiazole was shown to inhibit thiamine biosynthesis (941). Nrridazole (419) affects iron metabohsm (850). The dehydrase for 5-aminolevulinic acid of mouse liver is inhibited by 2-amino-4-(iS-hydroxy-ethyl)thiazole (420) (942) (Scheme 239). l-Phenyl-3-(2-thiazolyl)thiourea (421) is a dopamine fS-hydroxylase inhibitor (943). Compound 422 inhibits the enzyme activity of 3, 5 -nucleotide phosphodiesterase (944). The oxalate salt of 423, an analog of levamisole 424 (945) (Scheme 240),... 

Analytical and control methods for acetic anhydride are fully discussed in reference 55. Performance tests are customarily used where the quality of the product is cmcial, as in food or pharmaceutical products. Typical specifications are ... 

The value of many chemical products, from pesticides to pharmaceuticals to high performance polymers, is based on unique properties of a particular isomer from which the product is ultimately derived. Eor example, trisubstituted aromatics may have as many as 10 possible geometric isomers whose ratio ia the mixture is determined by equiHbrium. Often the purity requirement for the desired product iacludes an upper limit on the content of one or more of the other isomers. This separation problem is a compHcated one, but one ia which adsorptive separation processes offer the greatest chances for success. 

Apart from the cleanout procedure, the analytical work performed during the production of a bulk pharmaceutical in a three-step synthesis includes 15 different analyses having deterrnination of 22 parameters for raw materials 15 different analyses having deterrnination of 17 parameters in process controls and 11 different analyses having deterrnination of 19 parameters for the product. 

Farm animals produce recombinant proteins less expensively than bacteria or cells in culture because the farm animals produce large volumes of milk containing up to 5 g/L of recombinant protein. In addition, modifications to the proteins that can be performed only by mammalian cells are made by the cells of the mammary gland. Therefore, numerous pharmaceuticals that previously could only be made by cells in culture or extracted from human tissue or blood are being produced by lactating farm animals. 

The number of microencapsulated commercial oral formulations available and the volume of these formulations sold annuaUy is comparatively smaU. This may reflect the difficulty of developing new dmg formulations and bringing them successfully to market or the fact that existing microencapsulation techniques have had difficulty economically producing mictocapsules that meet the strict performance requirements of the pharmaceutical industry. One appHcation that is a particularly active area of development is mictocapsules or microspheres for oral deUvery of vaccines (45,46). 

Cross-linked versions of water-soluble polymers swollen in aqueous media are broadly referred to as hydrogels (52) and have a growing commercial utility in such apphcations as oxygen-permeable soft contact lenses (qv) (53) (Table 4) and controUed-release pharmaceutical dmg deflvery devices (54). Cross-linked PVP and selected copolymers fit this definition and are of interest because of the following stmcture/performance characteristics ... 

L-Ascorbic acid is used as a micronutrient additive in pharmaceutical, food, feed, and beverage products, as weU as in cosmetic appHcations. The over-the-counter (OTC) vitamin market is strong, growing in demand, and vitamin C is available in the form of piUs and tablets to supplement the daily diet to maintain peak physical performance. 

Various aspects of the chromatography of vitamin B 2 and related corrinoids have been reviewed (59). A high performance Hquid chromatographic (hplc) method is reported to require a sample containing 20—100 p.g cyanocobalamin and is suitable for premixes, raw material, and pharmaceutical products (60). 

Process Economics. Relative economics of various ceU culture processes depend heavily on the performance of the ceU line in a system and on the cost of raw materials, particularly the medium. Models are usuaUy developed for the various processes using productivity data obtained from smaU-scale experiments (see Pilot AND MiCROPLANTs). Often, for high value products, the process which ensures the shortest time to market may be the process of choice because of other economic criteria. This is especially tme for pharmaceuticals (qv). RehabUity concerns also often outweigh economic considerations in choosing a process for a high value product. 

Much of the experimental work in chemistry deals with predicting or inferring properties of objects from measurements that are only indirectly related to the properties. For example, spectroscopic methods do not provide a measure of molecular stmcture directly, but, rather, indirecdy as a result of the effect of the relative location of atoms on the electronic environment in the molecule. That is, stmctural information is inferred from frequency shifts, band intensities, and fine stmcture. Many other types of properties are also studied by this indirect observation, eg, reactivity, elasticity, and permeabiHty, for which a priori theoretical models are unknown, imperfect, or too compHcated for practical use. Also, it is often desirable to predict a property even though that property is actually measurable. Examples are predicting the performance of a mechanical part by means of nondestmctive testing (qv) methods and predicting the biological activity of a pharmaceutical before it is synthesized. 

Kneading Devices These are closely related to the agitated pan but differ as being primarily mixing devices with heat transfer a secondary consideration. Heat transfer is provided by jacketed construction of the main body and is effected by a coolant, hot water, or steam. These devices are applicable for the compounding of divided solids by mechanical rather than chemical action. Apphcation is largely in the pharmaceutical and food-processing industries. For a more complete description, illustrations, performance, and power requirements, refer to Sec. 19. 

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