Complex drug substances, bioavailability

As described in Section 3.4.2, crospovidone can contribute to improving the dissolution and bioavailability of a drug, as a result of its disintegrating properties. However, these properties are inadequate for a number of drug substances, as their solubility in gastric juice is poor. In such cases it is worth considering complexing them with crospovidone in the same manner as with povidone (see Section 3.2.5.1). 

In the pharmaceutical industry, SSNMR is commonly used to study polymorphism, hydrogen bonding, crystal packing, and solid-solid interactions. Shelf life or activity decay is often determined by the bioavailability of different polymorphs. Fig. 12 shows very different CP/MAS spectra from two polymorphs of an analgesic, flufenamic acid. It is also used for the study of inclusion complexes, drug-excipient interactions, or the effect of moisture on drug substances or formulations. 

The ability to form complexes with such a large number of substances is a special feature of polyvinylpyrrolidone (Section 2.2.7). The complexes formed are almost always soluble and are stable only in an acid medium. This property can be used to increase the solubility of drugs in liquid dosage forms, as in the case of povidone-iodine. In solid dosage forms, the ability to form complexes is used to increase bioavailability. A reduction in the local toxicity of certain drugs can also be achieved by complexation with povidone. A special use for the complexation properties lies in the stabilization of proteins and enzymes in diagnostics. 

One problem with many of the active substances used today is their poor solubility in water and their limited bioavailability. One of the simplest means of improving the bioavailability of an active substance is to improve its dissolution by adding solubilizing agents, such as povidone. It forms water-soluble complexes with many active substances (see Sections 2.2.7 and 2.4.5). With some such substances, it may be sufficient to produce a physical mixture. Fig. 45 shows the improvement in the dissolution rate of reserpine achieved by simply mixing it with an excess of povidone K 30. For the mixture with indomethacin see Section 3.4.3.1. Similar results can be expected with the drugs listed in Section 2.4.5. That this effect also applies to finished preparations can be seen for phenytoin tablets in Fig. 52 [326]. The bioavailability of peroral gidazepam is increased by the addition of povidone too [536]. 

Copovidone can also be used as a matrix in certain rapid-dissolution dosage forms, depending on the other ingredients used [112, 475]. This should be of particular interest for drugs with relatively poor bioavailability, as copovidone forms complexes with these substances, increasing the dissolution rate in much the same manner as does povidone (see Section 2.4.3). 

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