Figure 2: Dissolution profiles for series 1 doses. The outer Labrafil (Gattefossé, St-Priest, France) capsule contains caffeine
(caff.), and the inner polyethylene glycol 6000 contained nicotinamide (nic.). Results after 0, 2, 3, and 5 months' storage
are shown. (FIGURE IS COURTESY OF THE AUTHOR)
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Self-emulsifying drug-delivery systems also may be used. These systems generally contain an oil and a surfactant and also
may contain a cosurfactant. The systems are suitable for compounds whose log P value is 2–4. For compounds with higher log P values, oils should be used. The related microemulsion products are homogeneous, clear fluid systems with small droplet size
(i.e., 100–600 nm) that comprise an aqueous phase, an oily phase, a surfactant, and a cosurfactant. They form spontaneously
on gentle mixing, are thermodynamically stable, and have low viscosity. The microemulsions include nonionics as surfactants,
derivatives of propylene glycol or polyglycerols as cosurfactants, and vegetable oils or fatty acid esters as oily components.
The proportions required for the various components may be established using pseudoternary phase diagrams to map out the microemulsion
domain where the fluid remains clear. Typical applications are in increasing bioavailability, varying the release profile,
improving stability, and handling potent or toxic compounds.
The semisynthetic and synthetic carriers referred to here are widely considered chemically inert, and their potential for
interaction with the active is thought to be low. However, the chemical compatibility of materials is not to be taken for
granted and should be the subject of standard initial compatibility testing. Even materials considered inert may be incompatible
with certain actives. PEG, for example, is incompatible with drugs such as penicillin and aspirin.
Figure 3: Dissolution profiles for series 2 doses. The outer Labrafil (Gattefossé, St-Priest, France) capsule contains caffeine
(caff.), and the inner polyethylene glycol 6000 coated capsule contained nicotinamide (nic.). Results after 0, 2, 3, and 5
months' storage are shown. (FIGURE IS COURTESY OF THE AUTHOR)
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Standard restrictions apply to carrier selection. Typically, water, aqueous solutions, and glycerol quickly soften hard-capsule
shells and should be avoided. Alcohol and low-molecular weight PEGs (e.g., PEG 400) dehydrate gelatine shells quickly, leading
to gross embrittlement within short periods (i.e., 24 h to a few days, according to the formulation). Formulators may, however,
consider the possibility of using a finely balanced content of, say, PEG 400 and water. Such formulations would require careful
evaluation
The nature of formulations using complex thermosoftening excipients raises issues of possible changes in dissolution on storage
because of short- or long-term polymorphic changes in the carrier These polymorphic changes could result in a decrease or
increase in dissolution on storage, with possible associated clinical significance. Here, changes may arise with respect to
both the active ingredient and the excipient and represent an important area of stability-test review for the dissolution
of such products.
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