Preformulative assessment of preformed complexes of gemfibrozil, with cyclodextrins.
The aim of this study is to carry out preformulative investigations on preformed inclusion complexes of the poorly water-soluble, lipid-lowering agent gemfibrozil and naturally occurring cyclodextrins (CDs). Phase solubility studies showed a linear AL- type diagram with alpha, beta, and y cyclodextrins, indicating the formation of inclusion complexes in a 1:1 molar ratio with all the three CDs. beta-CD-gemfibrozil complex having a maximum stability constant of 148.88 M(-1) was selected for preparation of preformed inclusion complex by kneading, co-precipitation, co-evaporation, and freeze-drying and compared with the physical mixture. The kneaded product was subjected to microwave-drying, with this mode of drying studied as an alternative method for preparation of the complex. The prepared complexes were assessed by equilibrium solubility analysis and intrinsic dissolution rate studies. Further characterization was done by differential scanning calorimetry, X-ray powder diffractometry, Fourier transform infrared spectroscopy, and scanning electron microscopy. The freeze-dried product was identified as the inclusion complex having the maximum intrinsic dissolution rate and hence was assessed for changes in permeability characteristics. pH partition studies and partial in vivo permeability studies showed no changes in the permeability of the freeze-dried product when compared to the pure drug.
Ain
Shabnam
S
Department of Pharmaceutics, Rajiv Academy for Pharmacy, Delhi Mathura Bypass, Mathura- 281001, Uttar Pradesh, India.
Philip
Betty
B
Pathak
Kamla
K
D000818:Animals; D002152:Calorimetry, Differential Scanning / Q000379:methods; D003505:Cyclodextrins / Q000737:chemistry*; D003890:Desiccation / Q000379:methods; D004355:Drug Stability; D005612:Freeze Drying / Q000379:methods; D015248:Gemfibrozil / Q000737:chemistry* / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D000960:Hypolipidemic Agents / Q000737:chemistry / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008855:Microscopy, Electron, Scanning / Q000379:methods; D008872:Microwaves; D010539:Permeability; D051381:Rats; D015203:Reproducibility of Results; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature; D014961:X-Ray Diffraction / Q000379:methods
D003505:Cyclodextrins; D000960:Hypolipidemic Agents; D015248:Gemfibrozil