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The ratio of solubility of a drug in octanol:aqueous phase is reported as its log P value. This is also known was the partition coefficient between octanol and water. This value captures the relative hydrophilic to lipophilic property of a particular compound, in biopharmaceutics this is the API. Following oral ingestion of a drug product, the solubility is measured within an aqueous system which drives absorption, yet the membrane permeability favours an unionised and lipophilic compound thus a balance of hydrophilic and lipophilic property is desirable for a drug. A log P value of <5 was reported as preferred.

It should be noted that human physiology is not as simple as a ratio between octanol and water. The aqueous phase within the gastrointestinal tract for example can vary from an acidic gastric media to a neutral pH within the small intestine. Therefore it is often more relevant to consider the partition coefficient between an aqueous buffer of the appropriate pH and octanol. Particular pH values of interest include the following: pH 7.4 (the pH of blood/serum); pH 6.5–6.8 (the pH within the small intestine) and pH 1–2 (the pH within the stomach).

Drug compounds that are not ionisable will show the same value of partition ratio across a full pH range. Many drugs are ionisable and thus the partition between octanol and an aqueous phase will differ according to their ionisation status. Ionised compounds are more polar and will thus favour the aqueous phase. This is shown schematically in Figure 3.2.

The distribution coefficient (D) (usually expressed as log D) is the effective lipophilicity of a compound at a given pH and is a function of both the lipophilicity of the unionised compound and the degree of ionisation.

Consider a weak acid; this compound will be unionised at low pH and thus will partition into octanol to a greater extent at lower pH values. An example of this is shown in Figure 3.3 for indomethacin which has a pK_a value of 4.5. Note that the log P value is the partition coefficient when the compounds under test are fully unionised. A log D value should always be reported with a pH value.

Figure 3.2 Schematic diagram to demonstrate the impact of ionisation on the partition of a compound between octanol and an aqueous phase.

Figure 3.3 Impact of log D vs pH for a compound with a pKa value of 4.5.