Drug solubility stability

Improvement of the properties of a drug may be achieved by the chemical modification of the parent drug. The preparation of an ester, salt, or other modification of the parent structure may be employed with parenteral drugs to increase stability, alter drug solubility, enhance depot action, avoid formulation... 

Many drugs require a certain pH range to maintain product stability. As discussed previously, drug solubility may also be strongly dependent on the pH of the solution. An important aid to the formulator is the information contained in a graph of the solubility profile of the drug as a function of pH (Fig. 2). The... 

Similarly to the solubility of active drugs, the solubility of surfactants that were used in CFC systems has significantly changed. Surfactant solubility in HFA 134a ranges from 0.005% to 0.02% w/v, much lower than the concentration required to stabilize suspensions (0.1-2.0% w/v) (24,42). The surfactants can be solubilized with the addition of cosolvents such as ethanol. However, it is most likely that cosolvents will be incompatible with suspension formulations because drug solubility will also be promoted and crystal growth will occur. 

As part of the preformulation activities, investigations include physiochemical character, purity, solubility, stability, and optimal pH studies. In preparation for clinical studies, potential product formulations considering route of administration and solution stability are also studied. Unique to dosage form development studies for lyophilized products, thermal analysis of the drug substance and product formulations are also necessary. Data generated during this phase of product development is useful for future development activities, along with validation. 

When a compound moves from discovery into development it is critical that the drug candidate s molecular properties are optimised in terms of bioavailability (solubility), stability, processability, hygroscopicity, etc. The compound... 

Factors that can affect bioavailability include metabolism (to be discussed in more detail in Chapter 3), lipid solubility of the drug, chemical stability of the drug (e.g., penicillin G is unstable at gastric pFI), and the nature of the drug formulation (i.e., particle size, salt form, presence of inert binders, etc.). 

Pharmaceutical applications of cyclodextrins have been studied the most extensively. The identified roles of cyclodextrins are primarily to increase solubility, stability, and the bio availability of drugs with limited water solubility, to reduce the side effects and toxicity of drugs, and to alter their physical properties such as smell and taste. There have been many excellent reviews on the pharmaceutical utilization of cyclo dextrin and its derivatives by Loftsson and Brewster [45],Rajewski and Stella [46], and Irie et al. [47]. 

The majority of the pharmaceutical drugs are weak bases or weak acids. Among the marketed drugs, more than 75% are weak bases, 25% are weak acids, and 5% are nonionic [38]. Therefore, knowledge of pK i is useful for enhancing drug solubility and stability. The Henderson-Hasselbalch equation is used to describe the ionization of a weak acid or base ... 

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