Preclinical Pharmacokinetic Evaluation of Efavirenz Solid Dispersions in Two New Modified Starches.

ABSTRACT

Efavirenz, a widely prescribed anti retroviral drug belong to Class II under BCS and exhibit low and variable oral bioavailability due to its poor aqueous solubility and it requires enhancement in solubility and dissolution rate for increasing its oral bioavailability. In our earlier studies solid dispersion of efavirenz in two new modified starches namely (i) starch citrate and (ii) starch phosphate has markedly enhanced the dissolution rate and dissolution efficiency of efavirenz. The objective of the present study is to evaluate the in vivo performance and pharmacokinetics of the efavirenz solid dispersions in the two new modified starches. Pharmacokinetic evaluation of efavirenz- starch citrate (12) and efavirenz- starch phosphate (12) solid dispersions was done in healthy rabbits weighing 1.5 – 2.5 kg (n=6) of either sex in a cross over RBD at a dose equivalent to 10 mg/kg of drug in comparison to efavirenz pure drug. All the pharmacokinetic parameters namely Cmax, Tmax, Ka and (AUC) 0 ∞ indicated rapid and higher absorption and bioavailability of efavirenz when administered as solid dispersion in the two new modified starches. A 9.90 and 9.14 fold increase in the absorption rate (Ka) was observed respectively with efavirenz- starch citrate (12) solid dispersion and efavirenz- starch phosphate (12) solid dispersion when compared to efavirenz pure drug. A 1.46 and 1.47 fold increase in (AUC) ∞ 0 was also observed respectively with these solid dispersions when compared to efavirenz pure drug. The solid dispersions of efavirenz in the two new modified starches (starch citrate and starch phosphate) exhibited markedly higher rates of absorption and bioavailability of efavirenz when compared to efavirenz alone in the in vivo evaluation.