Active Ingredient: Doxycycline
The rash resolves upon discontinuation of the drug. Absorption of tetracycline occurs in the stomach and the upper small intestine. Absorption of tetracyclines has been reported to be impaired by milk products, aluminum hydroxide gels, sodium bicarbonate, calcium and magnesium salts, laxatives containing magnesium and iron preparations.
The mechanisms responsible for decreased absorption appear to be chelation and an increase in gastric pH.
This improvement in drug dissolution rate had two main explanations. Firstly, solid state analysis of the powders showed that thalidomide and cyclodextrins partially interacted.
This interaction at the molecular level increased the drug solubility in aqueous environment as demonstrated in the phase solubility studies. The second positive contribution to thalidomide dissolution rate came from lecithin, owing to its surface-active properties.
The positive effect of lecithin on wettability increased the powder surface interacting with the solvent.
In vitro thalidomide transport across rabbit nasal mucosa In vitro THAL transport across excised rabbit nasal mucosa in a 4-h experiment was negligible from all powders, as well as from the thalidomide saturated solution.
Having observed that trans-mucosal diffusion was very low, if not absent, the THAL concentration in the receptor compartment was measured only at the end of the experiment.
The thalidomide present in the mucosa at the end of the permeation experiment was extracted from the tissue sample used as barrier. The amounts recovered are shown in the bar graph of Fig.
Any possible drug degradation occurring during the permeation was assessed by determining the thalidomide mass balance after all transport experiments Table 3.
In summary, the transport experiments showed that thalidomide was poorly diffused across the nasal epithelium, remaining to a certain extent in the tissue.
The negligible transport across the mucosa is a pivotal result with respect to topical application, because it reduces the likelihood of thalidomide being significantly absorbed from the nasal cavity into the systemic circulation.
Thus, thalidomide accumulation within the tissue is favourable to its local action.
The mechanism underlying this action has been related to the interaction with the nasal epithelial membranes and transient opening of tight junctions.
Several studies indicate different enhancing properties of b-cyclodextrin and derivatives depending on the substituting moiety.
In general, methylated derivatives appeared more effective compared to hydroxypropyl-b-cyclodextrin with respect to nasal absorption of drugs Merkus et al. The higher absorption enhancing effect of b-cyclodextrin compared to the other derivatives was also seen from the traces of thalidomide detected in the receptor compartment.