Basic drugs solubility

Figure 7 Behavior of two formulations of a poorly soluble, weakly basic drug (solubility characteristics shown in Figure 6) in media composed at two pHs—one to represent acidic conditions in the stomach, the other to represent the hypochlorhydric stomach. (A) Formulation with non-robust dissolution characteristics and (B) Formulation with robust dissolution characteristics.

If the solubility of a drug is to be reduced to enhance stability or to prepare a suspension, the for-mulator may prepare water-insoluble salts. A classic example is procaine penicillin G, the decreased solubility (7 mg/mL) of which, when compared with the very soluble penicillin G potassium, is utilized to prepare stable parenteral suspensions. Another alternative to preparing an insoluble drug is to use the parent acidic or basic drug and to buffer the pH of the suspension in the range of minimum solubility. 

The accelerated dissolution of soluble pure acidic or basic drugs, through the addition of acidic or basic components to the dissolution media, becomes significant when the concentration of added components approaches the intrinsic solubility of the drug. 

Figure 8 Transfer model for poorly soluble, weakly basic drugs.

Bergstrom CAS (2005) In silico predictions of drug solubility and permeability two rate-limiting barriers to oral drug absorption. Basic Clin Pharmacol Toxicol 96 156-161. 

For an acidic and basic drug, the solubility over the GI pH range varies depending on the intrinsic solubility (SD) of the compound (i.e., solubility of unionized or nonprotonated species), pfCa, and the solubility of the salt form.71 72... 

It is common practice in pharmaceutical industry to generate salt forms of a drug substance to improve solid-state properties and solubility. CE has proven its ability to analyze reliably organic acids (direct, indirect detection) and alkaline/earth alkaline metals and basic amino acids. For basic drugs, a non-toxic organic acid or inorganic acid is chosen as counterion. Acidic drug substances will usually be deprotonated by alkaline and earth alkaline... 

In the absence of a salt basic drugs will also have increased solubility in the acidic environment of the stomach. 

This equation applies to both acidic and basic drugs. Inspection confirms that the lower the pH relative to the pKa, the greater will be the fraction of drug in the protonated form. Because the uncharged form is the more lipid-soluble, more of a weak acid will be in the lipid-soluble form at acid pH, whereas more of a basic drug will be in the lipid-soluble form at alkaline pH. 

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