betadex and Cadaver

The aim was to evaluate ointments for local treatment of anal fissures. Nitroglycerin (NTG) was complexed with β-cyclodextrin (β-CD) to provide prolonged NTG release, with the intention of decreasing systemic drug absorption and thus reducing side effects.. Gels, creams and anhydrous water-emulsifying (AWE) ointment with NTG-CD were compared with preparations containing uncomplexed NTG (diluted with crospovidone, NTG-cP). The in-vitro NTG release and ex-vivo skin absorption were studied.. The prolonged-release ointment with the NTG-CD complex was formulated using AWE base or w/o cream (20% water); release of NTG from a hydrogel was very fast with both the complexed and uncomplexed forms. From the AWE ointment base, 16.4% or 4.5% of the total NTG dose was released after 6 h when NTG-cP or NTG-CD was incorporated, respectively. With the complexed form, NTG absorption to the skin after a 5-h application was 18.1 or 11.1 μg/g from AWE ointment or cream, respectively; absorption of the uncomplexed NTG was higher: 52.3 or 21.9 μg/g from AWE ointment and cream, respectively.. Complexation with β-CD results in prolonged release of NTG from AWE ointment and w/o cream, which was confirmed by the ex-vivo skin absorption results.

Topics: Adult; beta-Cyclodextrins; Cadaver; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Carriers; Female; Fissure in Ano; Humans; Hydrogels; In Vitro Techniques; Nitroglycerin; Ointments; Skin; Skin Absorption; Solubility

Enhanced skin penetration of hydrocortisone can be desirable for treatment of several diseases. Transdermal iontophoretic delivery of hydrocortisone solubilized in an aqueous solution of hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) was investigated and compared with chemical enhancement of co-solvent formulations. The passive permeation of hydrocortisone through human cadaver skin was higher when delivered from propylene glycol than when delivered after solubilization in an aqueous solution of HP-beta-CyD. However, the iontophoretic delivery of the 1% hydrocortisone-9% HP-beta-CyD solution was higher than the amount delivered passively by the 1% hydrocortisone-propylene glycol formulation, even if oleic acid was used as a chemical enhancer. Iontophoretic delivery of 1% hydrocortisone with 3% or 15% HP-beta-CyD was lower than that of the 9% HP-beta-CyD solution. These data suggest that free hydrocortisone rather than complexes is predominantly delivered iontophoretically through the skin and the HP-beta-CyD complex serves as a carrier to replenish depletion of hydrocortisone. HP-beta-CyD prevents hydrocortisone from forming a skin reservoir. Iontophoresis provides better enhancement of transdermal delivery of hydrocortisone than the chemical approach when just sufficient HP-beta-CyD is added to solubilize the hydrocortisone.

Topics: Administration, Cutaneous; Anti-Inflammatory Agents; beta-Cyclodextrins; Cadaver; Chemistry, Pharmaceutical; Cyclodextrins; Humans; Hydrocortisone; Iontophoresis; Permeability; Pharmaceutical Vehicles; Propylene Glycol; Skin Physiological Phenomena; Solvents