Relationship between lipophilicity of BCS class III and IV drugs and the functional activity of peroral absorption enhancers.
Absorption enhancers (AEs) have been shown to be specific in permeation enhancement capabilities because of which they increase absorption of some drug molecules more than others. Present study was designed to investigate the relationship between lipophilicity of drug molecules and the absorption enhancement potential of AEs. Four drug molecules of different lipophilicity were selected as model compounds, namely, cefotaxime sodium, ceftazidime pentahydrate, lovastatin and cyclosporin A. Their apparent permeability coefficients in the absence and presence of three classes of AEs (fatty acids, cyclodextrins, and bile salts) were determined using in vitro everted rat intestinal sac absorption model. Significant relationship was observed between log P of drug and absorption enhancement ratios by AEs. This relationship was found to be functionally directly or indirectly proportional depending upon nature of AE and explain the mechanism of permeation enhancement.
Sharma
Pradeep
P
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector No. 67, SAS Nagar 160062, Punjab, India.
Varma
Manthena V S
MV
Chawla
Harmander P S
HP
Panchagnula
Ramesh
R
D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry / Q000494:pharmacology*; D002439:Cefotaxime / Q000737:chemistry / Q000378:metabolism*; D002442:Ceftazidime / Q000737:chemistry / Q000378:metabolism; D003505:Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*; D016572:Cyclosporine / Q000737:chemistry / Q000378:metabolism*; D005227:Fatty Acids / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D008148:Lovastatin / Q000737:chemistry / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship
D001647:Bile Acids and Salts; D003505:Cyclodextrins; D005227:Fatty Acids; D016572:Cyclosporine; D008148:Lovastatin; D002442:Ceftazidime; D002439:Cefotaxime