Physical stability liquid dosage forms

Physical stability plays a role both for suspensions and solutions. A suspension may settle too fast and the sediment may be poorly resuspendable after standing for some time. Crystal growth too may occur in suspensions (see Sect. 18.4.2.3). In solutions, the active substance may crystallise during storage (Sect. 18.1.6). These physical stability problems resemble those of oral liquid dosage forms, see Sect. 5.4.14. 

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. 

For liquid formulations that are constituted by the pharmacist or patient, a separate shelf-life will be indicated before and after constitution. Physical stability before constitution means that the constituted formulation will still perform acceptably (i.e., dissolve or disperse) within the pre-constitution shelf-life. After constitution, the stability concerns will be similar to other liquid formulations. Even for solid-dosage forms, there can be a different shelf-life for the product as shipped (potentially with more protective packaging), and as received by the patient. 

The liquid formulation for parenteral administration requires additional physical and microbiological functionalities, such as syringeability, sterility, osmolarity, and pyrogen freedom. The particle size change can influence the syringeability of injection of a suspension formulation as well as the level of irritation at the site. Terminal sterilization such as autoclave or gamma irradiation may affect the physical stability of the dosage form. Both formulation and container systems should be evaluated [63]. 

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