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 (1:2) and efavirenz- starch phosphate (1:2) 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 (1:2) solid dispersion and efavirenz- starch phosphate (1:2) 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.
ABSTRACT
The objective of the study is to prepare, characterize and evaluate starch citrate, a new modified starch as a carrier in solid dispersions for enhancing the dissolution rate of efavirenz. The feasibility of formulating solid dispersions of efavirenz in starch citrate into compressed tablets with enhanced dissolution rate was also investigated. Starch citrate was prepared by reacting starch with citric acid at elevated temperatures. It was insoluble in water and has good swelling (1500%) property without pasting or gelling when heated in water. Solid dispersions of efavirenz in starch citrate were prepared by solvent evaporation method employing various weight ratios of drug: starch citrate such as 2:1(SD-1), 1:1(SD-2), 1:2(SD-3), 1:3(SD-4) and 1:9(SD-5) and were evaluated for dissolution rate and efficiency. All the solid dispersions prepared gave rapid and higher dissolution of efavirenz when compared to pure drug. A 12.94 and 40.41 fold increase in the dissolution rate (K1) of efavirenz was observed with solid dispersions SD-4 and SD-5 respectively. The DE30 was also increased from 10.66% in the case of efavirenz pure drug to 60.93% and 74.23% in the case of these solid dispersions. Efavirenz (50 mg) tablets were prepared employing efavirenz alone and its solid dispersions SD-3 and SD- 4 by wet granulation method and were evaluated. Efavirenz tablets formulated employing its solid dispersions in starch citrate gave rapid and higher dissolution rate and DE30 when compared to plain and commercial tablets. A 7.01 and 15.30 fold increase in the dissolution rate (K1) was observed with tablet formulations containing solid dispersions SD-3 and SD-4 respectively when compared to plain tablets.