Dosage physical stability

Pharmaceutical scientists have developed improved suspension dosage forms to overcome problems of poor physical stability and patient-perceived discomfort attributed to some active ingredients. An important development aspect of any suspension is the ability to resuspend easily any settled particles prior to instillation in the eye and ensure that a uniform dose is delivered. It would be ideal to formulate a suspension that does not settle since the patient may not always follow the labeled instructions to shake well before using. However, this is usually not feasible or desirable since the viscosity required to retard settling of the insoluble particles completely would likely be excessive for a liquid eyedrop. The opposite extreme, of allowing complete settling between doses, usually leads to a dense layer of agglomerated particles that are difficult to resuspend. 

Table 2.1 presents examples of the main classes of low-molecular-weight bioactive molecules which are currently considered to be helpful for human well-being and which can be therefore used as food supplements as well as active components in skin-care applications (Ratnam et al., 2006 McClements et al., 2009). The required physicochemical properties of effective bioactive compounds, which should be considered in the formulation of the prophylactic and therapeutic dietary supplements at their desired oral dosages, are described in the scientific literature. These properties are (i) solubility in aqueous media (ii) permeability through the gastrointestinal tract and cell membranes (iii) physical stability and (iv) bioavailability. 

Both chemical and physical stability must be assured in the development of solid dispersions. Since the drug is either molecularly dispersed or intimately mixed with the carrier, there is potential for greater chemical interaction between them. Any physical instability that leads to phase transformations may result in poor performance of dosage forms, including changes in dissolution rates and oral bioavailability. 

This article provides an overview of the properties and occurrence of amorphous pharmaceutical materials, and outlines their key applications in dosage form development. It describes their characteristics and the fundamental scientific basis for these characteristics. It also highlights the topical issues of chemical/ physical stability and polyamorphism. ... 

The chemical and physical stability of a drug can influence the choice of dosage form, the manufacturing... 

Emulsions have been widely used as vehicles for oral, topical, and parenteral delivery of medications. Although the product attributes of an emulsion dosage form are dependent on the route of administration, a common concern is the physical stability of the system, in particular the coalescence of its dispersed phase and the consequent alteration in its particle-size distribution and phase separation. The stabilization mechanism(s) for an emulsion is mainly dependent on the chemical composition of the surfactant used. Electrostatic stabilization as described by DLVO theory plays an important role in emulsions (0/W) containing ionic surfactants. For 0/W emulsions with low electrolyte content in the aqueous phase, a zeta potential of 30 mV is found to be sufficient to establish an energy maximum (energy barrier) to ensure emulsion stability. For emulsions containing... 

Dry syrups and instant granules are more important these days than finished suspensions, as the active ingredient is more stable in these dry products, and the physical stability requirements of the suspension, as the actual administration form, are not so critical. Because of their stability, dry syrups are often used as the dosage form for antibiotics. Instant granules are widely used for antacids,because of the possibility of microbial contamination with finished suspensions, for vitamins (plus minerals) for stability reasons, and for analgesics. 

Particle size and shape are important attributes of drug substances that can affect the dissolution rate, bioavailability, and the processing of oral solid dosage forms and the physical stability of semi-solid dosage forms. During manufacture of the bulk drug substance, the recrystallization conditions required to prepare a particular salt will inevitably influence the particle size and crystal habit conditions should be established early in the development program that routinely yield material with consistent characteristics. 

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