Dosage forms properties

Sterile products have several unique dosage form properties, such as freedom from micro-organisms, freedom from pyrogens, freedom from particulates, and extremely high standards of purity and quality however, the ultimate goal in the manufacture of a sterile product is absolute absence of microbial contamination. The emphasis of this chapter will be the validation of the sterilization processes responsible for achieving this goal. 

Surface area is one of the most important characteristics in particle technology. Particles with a different surface area will express different physical properties that will subsequently affect many applications and ultimately final dosage form properties. 

Since the ideal attributes of drug substances differ markedly for different dosage forms, properties appropriate to one dosage form may be inappropriate for another. For this reason, the drug substance attributes should suit the primary mode of delivery (i.e. oral, parenteral, inhalation, or other routes, if appropriate) and the dose (or dose range) required. If other dosage forms are developed, such as line extensions, at a future date, it may be necessary to counteract any adverse properties of the selected salt using suitable formulation techniques. 

To avoid confusion, several researchers have incorporated therapeutic intention into the definition of controlled release (4—7). Thus, controUed-release pharmaceuticals release dmgs in vivo according to a predictable, therapeutically rational, programmed rate to achieve the optimal dmg concentration in the minimal time (4). Specification by release rate complements specification by quantity jointly considered, they fix the duration of dmg release. Therefore, the dmg s duration of action can become a design property of a controlled release dosage form rather than an inherent pharmacokinetic property of the dmg molecule. 

The use of a bioadhesive, polymeric dosage form for sustained dehvery raises questions about swallowing or aspirating the device. The surface area is small, and patient comfort should be addressed by designing a small (less than 2 cm ), thin (less than 0.1 mm (4 mil) thick) device that conforms to the mucosal surface. The buccal route may prove useful for peptide or protein dehvery because of the absence of protease activity in the sahva. However, the epithelium is relatively tight, based on its electrophysiological properties. An average conductance in the dog is 1 mS/cm (57) as compared to conductances of about 27 and 10 mS/cm in the small intestine and nasal mucosa, respectively (58,59) these may be classified as leaky epitheha. 

Bourquin J, Schmidli H, van Hoogevest P, Leuenberger H. Pitfalls of artificial neural networks (ANN) modelling technique for data sets containing outlier measurements using a study of mixture properties of a direct compressed tablet dosage form. Eur J Pharm Sci 1998 7 17-28. 

For dry dosage forms, since it is their very low A which is their protechon against microbial attack, the moisture vapour properties of packaging materials requires careful examination. 

The fact that the GIT is so well perfused by the bloodstream permits efficient delivery of absorbed materials to the body. As a result of this rapid blood perfusion, the blood at the site of absorption represents a virtual sink for absorbed material. Under normal conditions, then, there is never a buildup in drug concentration in the blood at the site of absorption. Therefore, the concentration gradient will favor further unidirectional transfer of drug from the gut to the blood. Usually, then, blood flow is not an important consideration in drug absorption. Generally, the properties of the dosage form (especially dissolution rate) or the compound s inherent absorbability will be the limiting factors in absorption. 

In summary, the effect of pH on the dissolution rate of a drug from an oral dosage form depends on (a) the pH of the GI fluids, a patient variable (b) the acid or base strength of the drug, a pharmaceutical variable as well as (c) the physicochemical properties of the dosage form, another pharmaceutical variable. Furthermore, by intentionally designing the dosage form such that it buffers the diffusion layer, we can control a patient variable by a pharmaceutical variable. 

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. 

Suspensions are generally evaluated with respect to their particle size, electrokinetic properties (zeta potential), and rheological characteristics. A detailed discussion on the methods/techniques and relevant instrumentation is given in Sec. VII. A number of evaluating methods done specifically with suspension dosage forms, such as sedimentation volume, redispersibility, and specific gravity measurements, will be treated in this section. 

KOR Lehmann. Chemistry and application properties of polymethacrylate coating systems. In JW McGinity, ed. Aqueous Polymeric Coatings for Pharmaceutical Dosage forms, 2nd ed. New York Marcel Dekker, 1997, pp 101-176. 

The effectiveness of surfactants in overcoming the hydrophobic effect of magnesium stearate may not be a result solely of an increase in the wetting properties of the bulk phase. Compared to putting the surfactant in the dosage form, Botzolakis [71] and Wang and Chowhan [135] found that adding an equivalent amount of surfactant to the dissolution medium was not effective. The possible impact of the surfactant at... 

One of the most difficult parenteral dosage forms to formulate is a suspension. It requires a delicate balance of variables to formulate a product that is easily resuspended and can be ejected through an 18-to 21-gauge needle through its shelf life. To achieve these properties it is necessary to select and carefully maintain particle size distribution, zeta potential, and rheological properties, as well as the manufacturing steps that control wettability and surface tension. The requirements for, limitations in, and differences between the design of injectable suspensions and other suspensions have been previously summarized [17b, 18,19]. 

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