Effect of auxiliary substances on complexation efficiency and intrinsic dissolution rate of gemfibrozil-beta-CD complexes.
The studies reported in this work are aimed to elucidate the ternary inclusion complex formation of gemfibrozil (GFZ), a poorly water-soluble drug, with beta-cyclodextrin (beta-CD) with the aid of auxiliary substances like different grades of povidone(s) (viz. PVP K-29/32, PVP K-40, Plasdone S-630, and Polyplasdone XL), organic base (viz. triethanolamine), and metal ion (viz. MgCl(2).6H(2)O), by investigating their interactions in solution and solid state. Phase solubility studies were carried out to evaluate the solubilizing power of beta-cyclodextrin, in association with various auxiliary substances, to determine the apparent stability constant (K (C)) and complexation efficiency (CE) of complexes. Improvement in K (C) values for ternary complexes clearly proves the benefit of the addition of auxiliary substances to promote CE. Of all the approaches used, the use of polymer Plasdone S-630 was found to be the most promising approach in terms of optimum CE and K (C). GFZ-beta-CD (1:1) binary and ternary systems were prepared by kneading and lyophilization methods. The ternary systems clearly signified superiority over binary systems in terms of CE, solubility, K (C), and reduction in the formulation bulk. Optimized ternary system of GFZ-beta-CD-Plasdone S-630 prepared by using lyophilization method indicated a significant improvement in intrinsic dissolution rate when compared with ternary kneaded system. Differential scanning calorimetry, X-ray diffraction, Fourier transform infrared, scanning electron microscopy, and proton nuclear magnetic resonance were carried out to characterize the binary and optimized ternary complex. The results suggested the formation of new solid phases, eliciting strong evidences of ternary inclusion complex formation between GFZ, beta-CD, and Plasdone S-630, particularly for lyophilized products.
Sami
Fareen
F
Department of Pharmaceutics, Rajiv Academy for Pharmacy, Mathura 286001, Uttar Pradesh, India.
Philip
Betty
B
Pathak
Kamla
K
D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D005612:Freeze Drying; D015248:Gemfibrozil / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D004364:Pharmaceutical Preparations / Q000737:chemistry; D019999:Pharmaceutical Solutions / Q000737:chemistry / Q000378:metabolism; D011108:Polymers / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D014961:X-Ray Diffraction / Q000379:methods; D014965:X-Rays; D047392:beta-Cyclodextrins / Q000378:metabolism*
D004364:Pharmaceutical Preparations; D019999:Pharmaceutical Solutions; D011108:Polymers; D047392:beta-Cyclodextrins; D011205:Povidone; C031215:betadex; D015248:Gemfibrozil