Designing of quaternized hyperbranched polyamidoamines dendrimers: Surface activity, pharmaceutical efficacy, and safety approach

Abstract

The low solubility of the drug considers a major challenge for pharmaceutical formulation of both oral and parenteral products. In this work various generations of cationic hyperbranched polyamidoamine (PAMAM) quaternary ammonium salt dendrimers terminated with amine end groups were synthesized. The pharmaceutical application of these quaternized cationic surfactants ended with amine end groups and those ended with ester end groups which prepared in an earlier study were investigated. These dendrimers were compared as solubilizing agents for coenzyme Q10 (poorly soluble drug) and the dendrimers that showed high solubilizing potential (G2.5 C8, G2.5 C12) were selected to be evaluated as a dendrimer in dissolution study for coenzyme Q10 or Ledipasvir drug. In our investigation a comparison between four dissolution media with different surfactants namely, G2.5 C8, G2.5 C12, CTAB and Labrasol used for the dissolution test of Q10 was carried out. The results revealed that % Q10 released after 4 h was 86.7, 70.5, 43 and 10.5% for these dissolution media, respectively. These results indicated the priority of the synthesized cationic surfactants than the known commercial cationic surfactant (CTAB) or than Labrasol as recommended surfactant in previous lectures. Therefore, the profiles of the ledipasvir dissolution in the three-dissolution media (G2.5 C8, G2.5 C12 and FDA surfactant (1.5% tween 80 and 0.0075 mg/ml Butylated Hydroxytoluene (BHT)) are similar. The obtained results emphasized that the new surfactants can be used as alternative to FDA surfactant in the dissolution media of Ledipasvir.Eventually, the toxicity study was performed for two selected compounds from the prepared dendrimers, and these compounds were proved to be safe.