Product formulations

The design of the formulation of capsules and oral powders and that of tablets are similar in some respects, but there are also some important differences. In this section, the general aspects of formulation design are discussed. 

The acceptance is generally a non-linear function of perceived intensity. A simple example is the salt level in a soup which clearly has a level of maximum acceptability between too weak and too salty a taste. 

The experimental designs discussed in Chapters 24-26 for optimization can be used also for finding the product composition or processing condition that is optimal in terms of sensory properties. In particular, central composite designs and mixture designs are much used. The analysis of the sensory response is usually in the form of a fully quadratic function of the experimental factors. The sensory response itself may be the mean score of a panel of trained panellists. One may consider such a trained panel as a sensitive instrument to measure the perceived intensity useful in describing the sensory characteristics of a food product. 

Meilgaard, G.V. Civille and B.T. Carr, Sensory Evaluation Techniques, 2nd Edition. CRC Press, Boca Raton, FL, 1987. 

MacFie, Data Analysis in Ravour Research Achievements, Needs and Perspectives, in Ravour Science and Technology, M. Martens, G.A. Dalen and H. Russwurm Jr (Editors). Wiley, 1987. 

Stone and J.L. Sidel, Sensory Evaluation Practices, 2nd ed. Academic Press, San Diego, 1993. 

One of the main factors affecting crystallization in solution systems is the water content, or total solids content. This determines supersaturation and the subsequent rate kinetics as tempera- 

Addition of other components or ingredients also can influence nucleation and growth kinetics. For example, addition of 

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Sprays. Aerosol spray emulsions are of the water-in-oil type. The preferred propellant is a hydrocarbon or mixed hydrocarbon—hydrofluorocarbon. About 25 to 30% propellent, miscible with the oil, remains in the external phase of the emulsion. When this system is dispensed, the propellant vaporizes, leaving behind droplets of the w/o emulsion (Fig. 2b). A vapor tap valve, which tends to produce finely dispersed particles, is employed. Because the propellant and the product concentrate tend to separate on standing, products formulated using this system, such as pesticides and room deodorants, must be shaken before use. 

Biological characterization includes toxicological studies, dose relationships, routes of adininistration, identification of side effects, and absorption, distribution, metaboHsm, and excretion patterns. If the results are stiU acceptable, product formulation and dosage form are developed. The product should be pleasing to the patient and thus may contain flavoring and colorants. 

The Hercules viscometer was originally designed for paper and paperboard coatings, but its use has been extended to paints, adhesives, mineral slurries, emulsions, and starch solutions. The iastmment, noted for being robust and rehable, is particularly well suited for quaUty control and product formulation. It is capable of measuting viscosity over a moderate range 1-10 mPa-s) up to high shear rates (115,000 ). A more recent model is the... 

Soap as used in personal cleansing products has a long safe history of use. Modem soaps have been specifically formulated to be compatible with skin and to be used on a daily basis with minimal side effects. Excessive use of soap for skin cleansing can dismpt the natural barrier function of skin through the removal of skin oils and dismption of the Hpid bdayer in skin. This can result in imperfect desquamation or a dry appearance to skin and cause an irritation response or erythema, ie, reddening of the skin. Neither of these is a permanent response and the eHcitation of this type of skin reaction depends on the individual s skin type, the product formulation, and the frequency of use. 

R. M. Berry and E. D. MagH, "Chemical Grouting What s New and What s Being Done This Decade," unpubHshed manuscript, 1992 contains tables of grouting products, formulation viscosities, as well as pricing information available from Avanti International, Webster, Tex. 

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. 

In 1943 the reaction of anhydrous RhCl and CO at 80°C under pressure with a haUde acceptor, such as copper, was reported to produce a black crystalline product formulated as Rh4(CO) (42). The correct stmcture of the complex was... 

Powder products formulated with too much hydroxide can be hygroscopic and thus tend to go solid in storage rather than remaining as free-flowing powders. 

There is wide variation in the activity, specificity, compatibility, and mode of action of the many individual raw material organics used in product formulations. The quality of some raw materials, and ultimately supplier formulations, may be suspect. Not all competitive polymers or formulated products provide equal performance for an equivalent price. 

Amines can be blended into multifunctional product formulations containing alkali, polymer, and phosphate and where sulfite- or hydrazine-based oxygen scavengers are part of the formula, but not where tannins are employed. Amines must be fed separately from tannins. 

FIG. 24 Effect of partial replacement of linear alkylbenzesulfonate by a-olefinsulfonate (AOS) in surfactant component of carbonate-built product formulation on detergency of polyester-cotton (50 50 blend). (From Ref. 3.)... 

Initial hydrolysis would therefore lead to further hydrolysis and pH drop in storage tanks, resulting in a product that is difficult to recover and may cause irreparable damage (corrosion) in tanks, pipelines, and pumps. Therefore the pH must be kept high (9-11) to avoid acid material entering bulk storage (steep titration curve). If for product formulation requirements a product of pH 6-7 is essential, the use of buffers, e.g., phosphoric acid or citric acid, is recommended. 

As was pointed out, refinement of ethoxysulfated alcohols is sometimes required to satisfy current standards for product quality, in particular 1,4-di-oxane content. Due to the particular characteristics and outstanding suitability of FAES for application in personal care detergent products, the commercially accepted content of 1,4-dioxane in FAES has been progressively reduced to meet the demand of higher safety margins for the end-users, without requiring any change in product formulation and choice of surfactant. 

Bioavailability studies play a critical role in the evaluation of product formulations throughout the entire development process. 

Biphenyltetramine and l-(perfluoroheptyl)-2-phenylglyoxal gave a product formulated as 3,3 -bis(perfluoroheptyl)-2,2 -diphenyl-6,6 -biquinoxaline (169) (m-cresol, 20°C, 24 h 92% possibly containing both other possible... 

Benzoyl-2,3-dichloroquinoxaline (212) and 6-benzoyl-2,3(l//,4//)-quinoxali-nedione (213) gave a product formulated as 2,10-dibenzoyl[l,4]dioxino[2,3-b 5,6-fc ]diquinoxaline (214) [synthon (213), KOH, Me2NCHO, reflux. 

Chloro-2-(A(-ethylhydrazmo)qumoxalme 4-oxide with diethyl 1,3-acetonedi-carboxylate (Et02CCH2C0CH2C02Et) gave only one product, formulated on spectral evidence as ethyl 7-chloro-3-ethoxycarbonylmethyl-l-ethyl-l,2-dihydropyridazino[3,4-fo]qumoxalmeM-carboxylate (280 or tautomer) (AcOH, trace H2SO4, reflux, 5 h 80%). ... 

Perhaps the most convincing argument in favor of intercalant ionization derives from the analogous reaction of graphite with OsFg (B22). The product, formulated as CJOsFs, obeys the Curie-Weiss law, and has a magnetic moment characteristic of OsFs(V) salts. 

PECs have been calculated for various scenarios (production, formulation, and use) as a means to conduct a risk assessment. 

Drug substance/drug product purity, potency, and other testing Drug substance/drug product stability testing Method development, validation, and transfer Drug product formulation development... 

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. 

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