Transdermal delivery of carvedilol containing glycyrrhizin and chitosan as permeation enhancers: biochemical, biophysical, microscopic and pharmacodynamic evaluation.
The present study was aimed at unveiling the influence of glycyrrhizin and chitosan on rat epidermis and to correlate these effects with percutaneous permeation characteristics of carvedilol. The permeation of carvedilol across excised rat epidermis was significantly higher (p < 0.05) when glycyrrhizin, chitosan, or glycyrrhizin-chitosan mixture was used as a donor vehicle as compared to propylene glycol:ethanol (7:3) mixture. Epidermis obtained after 12 hr treatment of viable rat skin with a glycyrrhizin-chitosan mixture showed significantly higher (p < 0.05) permeability to carvedilol as compared to that after treatment with glycyrrhizin or chitosan alone. Further, the application of patches containing glycyrrhizin-chitosan mixture resulted in sustained release of carvedilol, which was able to control the hypertension in deoxycorticosterone acetate induced hypertensive rats through 28 hr. Estimation of microconstituents in rat epidermis revealed maximum extraction of cholesterol, sphingosine, and triglycerides after treatment with glycyrrhizin-chitosan mixture. This was manifested in altered lipid and protein-specific thermotropic transitions. Further, increase in intercellular space, disordered lipid structure and corneocyte detachment as observed in SEM and TEM suggests great potential of glycyrrhizin for use as a percutaneous permeation enhancer.
Sapra
Bharti
B
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India.
Jain
Subheet
S
Tiwary
A K
AK
D000277:Adjuvants, Pharmaceutic / Q000737:chemistry*; D000279:Administration, Cutaneous; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002152:Calorimetry, Differential Scanning; D002227:Carbazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077261:Carvedilol; D048271:Chitosan / Q000737:chemistry*; D002784:Cholesterol / Q000032:analysis; D003692:Delayed-Action Preparations; D003900:Desoxycorticosterone; D016503:Drug Delivery Systems; D004357:Drug Synergism; D004817:Epidermis / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D019695:Glycyrrhizic Acid / Q000737:chemistry*; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D010539:Permeability / Q000187:drug effects; D011412:Propanolamines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption / Q000187:drug effects; D012995:Solubility / Q000187:drug effects; D013110:Sphingosine / Q000032:analysis; D013501:Surface-Active Agents / Q000737:chemistry; D014280:Triglycerides / Q000032:analysis
D000277:Adjuvants, Pharmaceutic; D000959:Antihypertensive Agents; D002227:Carbazoles; D003692:Delayed-Action Preparations; D011412:Propanolamines; D013501:Surface-Active Agents; D014280:Triglycerides; D000077261:Carvedilol; D003900:Desoxycorticosterone; D019695:Glycyrrhizic Acid; D048271:Chitosan; D002784:Cholesterol; D013110:Sphingosine