Effect of Pvp on Cyclodextrin Complexation of Efavirenz for Enhancing Its Solubility and Dissolution Rate

Efavirenz belongs to Class II under BCS and exhibit low and variable bioavailability due to its poor aqueous solubility. As such it needs enhancement in the dissolution rate and bioavailability to derive its maximum therapeutic efficacy. The objective of the present investigation is to study the complexation of efavirenz with two cyclodextrins, βcyclodextrin (βCD) and hydroxypropyl β-cyclodextrin (HPβCD) alone and in the presence of polyvinyl pyrrolidone (PVP) by phase solubility study and to evaluate the feasibility of enhancing the solubility and dissolution rate of efavirenz employing the two cyclodextrins alone and with PVP. Solid inclusion complexes of efavirenz-βCD and efavirenz -HPβCD in 1:1 and 1:2 ratios were prepared with and without PVP K30 by three methods namely (i) physical mixing, (ii) kneading and (iii) co-precipitation and were evaluated. The aqueous solubility of efavirenz was linearly increased as a function of the concentration of βCD and HPβCD alone and in the presence of PVP K30. The increase in solubility is due to the formation of a 1:1 M complex in solution in each case. The complexes formed between efavirenz-CD were quite stable. Addition of PVP has markedly enhanced the complexation and solubilizing efficiencies of βCD and HPβCD. The CD complexes of efavirenz prepared employing βCD and HPβCD alone and with PVP exhibited marked enhancement in the dissolution rate and dissolution efficacy of efavirenz. HPβCD gave higher enhancement in the dissolution rate and efficiency when compared to βCD. Complexes prepared by kneading method gave higher dissolution rate and DE30 values than those prepared by coprecipitation and physical mixing methods. The solid inclusion complexes of βCD and HPβCD with PVP gave higher rates of dissolution than those of efavirenz and its complexes with CDs alone. EfavirenzβCD (1:2) kneaded complex gave a 10.42 fold increase in the dissolution rate of efavirenz, whereas in the presence of PVP K30, it gave a 26.28 fold increase. Efavirenz-HPβCD (1:2) kneaded complex gave a 24.41 fold increase in the dissolution rate of efavirenz, whereas in the presence of PVP K30, it gave a 46.64 fold increase. Hence a combination of CDs (βCD, HPβCD) with PVP K30 is recommended to enhance the solubility and dissolution rate of efavirenz, a BCS class II drug.