Novel oleic acid derivatives enhance buccal permeation of didanosine

Abstract

The aim of this study was to explore the potential of novel oleic acid (OA) derivatives as buccal permeation enhancers for the delivery of didanosine (ddI). The OA derivatives, i.e. ester derivative (OA1E), the dicarboxylic acid derivative (OA1A) and the bicephalous dianionic surfactant (OA1ANa) were synthesized and their effects were compared to the parent OA. OA, OA1E, OA1A and OA1ANa at 1% w/w all showed potential for enhancing the buccal permeability of ddI with enhancement ratio (ER) of 1.29, 1.33, 1.01 and 1.72, respectively. OA1ANa at 1% w/w demonstrated the highest flux (80.30 ± 10.37 µg cm(-2 )h), permeability coefficient (4.01 ± 0.57 × 10(-3) cm h(-1)) and ER (1.72). The highest flux for ddI (144.00 ± 53.54 µg cm(-2 )h) was reported with OA1ANa 2% w/w, which displayed an ER of 3.09 more than that with ddI alone. At equivalent concentrations, OA1ANa (ER = 3.09) had a significantly higher permeation-enhancing effect than its parent OA (ER = 1.54). Histomorphological studies confirmed that OA1ANa at all concentrations (0.5, 2.0 and 6.0% w/w) had no adverse effects on the mucosae. Morphological changes such as vacuoles formation and increased intercellular spaces were attributed to the buccal permeation-enhancing effect of OA1ANa. This study demonstrated the potential of novel OA derivatives as buccal permeation enhancers. OA1ANa at 2% w/w was also identified as the optimal novel OA derivative to widen the pool of fatty acid derivatives as chemical permeation enhancers for buccal drug delivery.

Novel dendritic derivatives of unsaturated fatty acids as promising transdermal permeation enhancers for tenofovir

“…12,39 All the derivatives synthesized in this study had a higher lipophilicity as compared to their respective parent FA as indicated by the calculated log P values (Table 3). The study further determined the effect of structural modifications to the UFAs via the transformation of carboxylic acid function into a branched tert-butyl ester function on the permeation enhancement efficacy.…”

“…Although the increases in the permeability parameters by the parent PA were not significantly different from the control, the increases in the permeability parameters by the derivative PA1E 2 were significantly different from the control ( p = 0.0039) ( Table 1). Studies have shown that an increase in enhancer lipophilicity results in an increase in permeation, 12,38,39,63 also possible ionic conjugation between basic dendritic derivatives and the acidic drug could aid in the movement of the TNF across the epidermis of the skin. 4).…”

“…22 The ER achieved by 2% w/w LLA1E 4 is comparable to that achieved by 5% (w/w) of either N-methyl-2-pyrrolidone (NMP) or transcutol P, which in an independent study displayed ER of 6.99 and 6.28 respectively for the transdermal delivery of daphnetin. 39 Previous studies report that FA at higher concentrations in gel formulations could also slow down the partitioning of the drug from the formulation thereby decreasing the amount of drug permeating. With an increase in the concentration of the lipophilic enhancer in the drug formulation, there would be a corresponding increase in the lipophilicity of the formulation.…”

“…12,31,33 A large selection of saturated and unsaturated fatty acids (UFAs) such as lauric acid, myristic acid, capric acid, oleic acid (OA), palmitoleic acid (PA), linoleic acid (LA), linolenic acid (LLA) and arachidonic acid (AA) have been studied as transdermal permeation enhancers. 12,27,[36][37][38][39] Therefore, there is a justified need to synthesize novel derivatives from compounds that display positive CPE properties. In addition literature shows evidence that saturated FAs are less effective in enhancing transdermal permeation as compared to their unsaturated counterparts.…”

Spray-dried didanosine-loaded polymeric particles for enhanced oral bioavailability

“…Owing to toxicity, reduced efficacy and inconvenient dosing requirements, the WHO has recommended the replacement of ddI by another NRTI, lamivudine [21]. At the same time, it still represents a therapeutic alternative in the poorest countries hit by the scourge [22] and an excellent model drug for the investigation of novel drug delivery systems and production processes [23,24].…”