Impact of sodium dodecyl sulphate on the dissolution of poorly soluble drug into biorelevant medium from drug-surfactant discs.

The purpose was to elucidate the mechanism of action of sodium dodecyl sulphate (SDS) on drug dissolution from discs under physiologically relevant conditions. The effect of incorporating SDS (4-30%, w/w) and drug into discs on the dissolution constant and solubility were evaluated for the poorly soluble drugs griseofulvin and felodipine in a biorelevant dissolution medium (BDM). Dissolution constants from dissolution profiles of drug discs with and without SDS were measured using miniaturized rotating disc dissolution. Solid state changes were investigated by X-ray diffraction. Solubility was determined using HPLC-UV. The interaction between micelles in BDM and SDS was investigated by isothermal titration calorimetry and dynamic light scattering. Isothermal titration calorimetry showed that SDS formed mixed micelles with bile salt:phospholipid (BS:PC) micelles in BDM. Dynamic light scattering showed that the addition of SDS made the BS:PC micelles grow up to 2.5 times in volume. As a function of SDS addition, the dissolution constant showed an apparent exponential increase, while drug solubility showed a weak linear dependence. The pronounced effect on dissolution constant with SDS in the discs is not caused by an increased surface area as SDS dissolves, micelles in the bulk medium or changes in the solid state properties of the drugs. The proposed mechanism involves a high local concentration of SDS at the solid-liquid interface as SDS dissolves and this solubilizes the drug. The improved solubility at the solid-liquid interface provided a much steeper concentration gradient resulted in a faster dissolution. The total amount of SDS in the discs only gave a minor increase in total surfactant concentration in the dissolution medium and did therefore not to any large extent affect the drug solubility in the bulk.

A mechanistic based approach for enhancing buccal mucoadhesion of chitosan.

Mucoadhesive buccal drug delivery systems can enhance rapid drug absorption by providing an increased retention time at the site of absorption and a steep concentration gradient. An understanding of the mechanisms behind mucoadhesion of polymers, e.g. chitosan, is necessary for improving the mucoadhesiveness of buccal formulations. The interaction between chitosan of different chain lengths and porcine gastric mucin (PGM) was studied using a complex coacervation model (CCM), isothermal titration calorimetry (ITC) and a tensile detachment model (TDM). The effect of pH was assessed in all three models and the approach to add a buffer to chitosan based drug delivery systems is a means to optimize and enhance buccal drug absorption. The CCM demonstrated optimal interactions between chitosan and PGM at pH 5.2. The ITC experiments showed a significantly increase in affinity between chitosan and PGM at pH 5.2 compared to pH 6.3 and that the interactions were entropy driven. The TDM showed a significantly increase in strength of adhesion between chitosan discs and an artificial mucosal surface at pH 5.2 compared to pH 6.8, addition of PGM increased the total work of adhesion by a factor of 10 as compared to the wetted surface without PGM. These findings suggest that chitosan and PGM are able to interact by electrostatic interactions and by improving the conditions for electrostatic interactions, the adhesion between chitosan and PGM becomes stronger. Also, the three complementary methods were utilized to conclude the pH dependency on mucoadhesiveness.