Pharmaceutical products formulation

The first recorded reference to the use of expert systems in pharmaceutical product formulation was in the London Financial Times in the spring of 1989 [3], closely followed by an article in the autumn of the same year [4], Both referred to the work then being undertaken by personnel at ICI Pharmaceuticals, UK (now AstraZeneca) to develop an expert system for formulating pharmaceuticals ab initio. Since that time several companies and academic institutions have reported their experiences. 

RC Rowe, RJ Roberts. Artifical intelligence in pharmaceutical product formulation neural computing and emerging technologies. PSTT l(5) 200-205, 1998. 

Reference to the use of expert systems in pharmaceutical product formulation first appeared on 27 April 1989 in the London Financial Times (Bradshaw 1989). This article was closely followed by one in the same year by Walko (1989). Both these authors were describing the work being undertaken by ICI (now Zeneca) Pharmaceuticals and Logica UK Ltd. to develop an expert system for formulating pharmaceuticals using PFES. Since these first publications, many companies and academic institutions have published on work being conducted in this area, as shown in Table 8.3. 

Rowe, R. C. 1997. Intelligent software systems for pharmaceutical product formulation. Pharm. Tech. 21 178-188. 

Sodium nitrate is also used in formulations of heat-transfer salts for he at-treatment baths for alloys and metals, mbber vulcanization, and petrochemical industries. A mixture of sodium nitrate and potassium nitrate is used to capture solar energy (qv) to transform it into electrical energy. The potential of sodium nitrate in the field of solar salts depends on the commercial development of this process. Other uses of sodium nitrate include water (qv) treatment, ice melting, adhesives (qv), cleaning compounds, pyrotechnics, curing bacons and meats (see Food additives), organics nitration, certain types of pharmaceutical production, refining of some alloys, recovery of lead, and production of uranium. 

Use as Solvent. Toluene is more important as a solvent than either benzene or xylene. Solvent use accounts for ca 14% of the total U.S. toluene demand for chemicals. About two-thirds of the solvent use is in paints and coatings the remainder is in adhesives, inks, pharmaceuticals, and other formulated products utilizing a solvent carrier. Use of toluene as solvent in surface coatings has been declining, primarily because of various environmental and health regulations. It is being replaced by other solvents, such as esters and ketones, and by changing the product formulation to use either fully soHd systems or water-based emulsion systems. 

Hussain AS, Shivanand P, Johnson RD. Application of neural computing in pharmaceutical product development computer aided formulation design. Drug Dev Ind Pharm 1996 20 1739-52. 

Principles of the methods employed to sterilize pharmaceutical products are described in Chapter 20. The British Pharmacopoeia (1993) recommends autoclaving and filtration as suitable methods applicable to aqueous liquids, and dry heat for non-aqueous and dry sohd preparatiorrs. The choice is determined largely by the ability of the formulation and container to withstand the physical stresses apphed by moist heat... 

The number of the constituent phases of a disperse system can be higher than two. Many commercial multiphase pharmaceutical products cannot be categorized easily and should be classified as complex disperse systems. Examples include various types of multiple emulsions and suspensions in which solid particles are dispersed within an emulsion base. These complexities influence the physicochemical properties of the system, which, in turn, determine the overall characteristics of the dosage forms with which the formulators are concerned. 

Content uniformity and long-term stability of a pharmaceutical product are required for a consistent and accurate dosing. Aggregation of dispersed particles and resulting instabilities such as flocculation, sedimentation (in suspensions), or creaming and coalescence (in emulsions) often represent major problems in formulating pharmaceutical disperse systems. 

Couto et al. [11] developed a flow injection system with potentiometric detection for determination of TC, OTC, and CTC in pharmaceutical products. A homogeneous crystalline CuS/Ag2S double membrane tubular electrode was used to monitor the Cu(II) decrease due to its complexation with OTC. The system allows OTC determination within a 49.1 1.9 x 103 ppm and a precision better than 0.4%. A flow injection method for the assay of OTC, TC, and CTC in pharmaceutical formulations was also developed by Wangfuengkanagul et al. [12] using electrochemical detection at anodized boron-doped diamond thin-film electrode. The detection limit was found to be 10 nM (signal-to-noise ratio = 3). 

It is evident even to the casual observer that the vast majority of pharmaceutical products are administered as solid dosage forms, which are in turn produced by the formulation and processing of powdered solids. All too often characterization of raw materials and products has centered on aspects of chemical purity, with only passing attention being given to the physical properties of the solids. However, every pharmaceutical scientist knows of at least one instance in which a crisis arose due to some variation in the physical properties of input materials, and in which better characterization would have prevented the problem. 

Product quality, purity and consistency are critically important in the pharmaceutical sector, applying to all stages of the supply chain and final dosed product. The human body is an exceptionally complex system and the full effect of a pharmaceutical product, consisting of the API, impurities and formulation components, is impossible to predict from first principles. The industry relies on rigorous clinical trials to assess drug efficacy, toxicity and side effect profiles. 

The formulation science used in the manufacture of pharmaceutical products is a complex discipline in its own right, and largely outside of the scope of this chapter only a very brief overview will be presented here. 

In flavoring liquid pharmaceutical products, the flavoring agent is added to the solvent or vehicle component of the formulation in which it is most soluble or miscible. That is, water-soluble flavorants are added to the aqueous component of a formulation and poorly water-soluble flavorants are added to the alcoholic or other nonaqueous solvent component of the formulation. In a hydroalcoholic or other multisolvent system, care must be exercised to maintain the flavorant in solution. This is accomplished by maintaining a sufficient level of solvent in which the flavorant is soluble. 

Pharmaceuticals, for the purpose of this book, means chemical compounds that are used in pharmaceutical production. This can comprise the active ingredient, which is also called active pharmaceutical ingredient (API) or drug substance or drug product and the inert pharmaceutical ingredients (excipients) that are used to formulate a drug product in the form of tablets, capsules, ointments, creams, lotions, parenterals, inhalers, and a variety of drug delivery systems. 

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