Effect of neat and binary vehicle systems on the solubility and cutaneous delivery of piperine.

Vitiligo is a skin disease characterized by depigmentation disorders due to lack of melanin production. Piperine, an alkaloid extracted from black piper, is active in melanocytes proliferation. To achieve this, the drug has to reach the melanocytes which exist in the deep layer of the epidermis. Higher drug concentration can be obtained after application of optimized formulation to skin. Accordingly, the aim of this work is to investigate the effect of vehicles on skin penetration of piperine as the first step in development of optimized formulation. The tested vehicles include ethanol (Eth), propylene glycol (PG), polyethylene glycol 400 (PEG), and oleic acid (OA) and their combinations. Water was used as the control and skin permeation was monitored using rabbit ear model skin. The highest piperine solubility (48.6 mg/ml) and flux (40.8 µg/cm2 h) was achieved by Eth and the lowest piperine flux (1.17 µg/cm2 h) was reported for PEG. PG and OA showed piperine flux values comparable to that of the control. Among different combination systems, Eth-OA (75:25) binary system had the highest piperine flux (59.3 µg/cm2 h) followed by Eth-OA (50:50) (32.3 µg/cm2 h) and PG-OA (90:10) (22.7 µg/cm2 h). The study thus introduced a vehicle system as the first step in the development of topical formulation of piperine.

Vascular sclerosing effects of bleomycin on cutaneous veins: a pharmacopathologic study on experimental animals.

BACKGROUND:: Varicose veins and the complications of venous disease are common disorders in humans. OBJECTIVE:: To study the effects of bleomycin as a potential new sclerosing agent and its adverse events in treating varicose veins. METHODS:: Bleomycin-loaded liposomes 0.1ml was injected in the dorsal ear veins of white New Zealand rabbits. Sodium tetradecyl sulfate was used as a positive control. Normal saline was used as negative control. The blood vessels of the treated ears were photographed before and at one hour and two, eight and 45 days after treatment. Biopsies from the treated areas were obtained for histological examination. Blood samples were collected to determine any possible toxicity. RESULTS:: Bleomycin by itself was ineffective; therefore, liposomes were used as a vector to deliver bleomycin to the vein lumen. Subsequently, bleomycin started showing its sclerosing effects. Toxicity monitoring showed no apparent hematologic, pulmonary, hepatic or renal toxicities. This study revealed that bleomycin induced vasculitis, which led to vascular occlusion, which was observed on day 1 and day 8. No bleomycin-related injury was noted by histopathological examination of lung sections. The calculation of the lung/body weight coefficient indicated that edema was present in the experimental groups compared with the negative and positive controls. STUDY LIMITATIONS:: Relatively small number of experimental animals used. CONCLUSIONS:: This study showed that bleomycin-loaded liposomes were able to induce vasculitis and vascular occlusion without any toxicity or complications. It might be useful, hence, to treat patients suffering from Varicose veins and other ectatic vascular diseases with this agent.

Vascular sclerosing effects of bleomycin on cutaneous veins: a pharmacopathologic study on experimental animals

Abstract: Background: Varicose veins and the complications of venous disease are common disorders in humans. Objective: To study the effects of bleomycin as a potential new sclerosing agent and its adverse events in treating varicose veins. Methods: Bleomycin-loaded liposomes 0.1ml was injected in the dorsal ear veins of white New Zealand rabbits. Sodium tetradecyl sulfate was used as a positive control. Normal saline was used as negative control. The blood vessels of the treated ears were photographed before and at one hour and two, eight and 45 days after treatment. Biopsies from the treated areas were obtained for histological examination. Blood samples were collected to determine any possible toxicity. Results: Bleomycin by itself was ineffective; therefore, liposomes were used as a vector to deliver bleomycin to the vein lumen. Subsequently, bleomycin started showing its sclerosing effects. Toxicity monitoring showed no apparent hematologic, pulmonary, hepatic or renal toxicities. This study revealed that bleomycin induced vasculitis, which led to vascular occlusion, which was observed on day 1 and day 8. No bleomycin-related injury was noted by histopathological examination of lung sections. The calculation of the lung/body weight coefficient indicated that edema was present in the experimental groups compared with the negative and positive controls. Study limitations: Relatively small number of experimental animals used. Conclusions: This study showed that bleomycin-loaded liposomes were able to induce vasculitis and vascular occlusion without any toxicity or complications. It might be useful, hence, to treat patients suffering from Varicose veins and other ectatic vascular diseases with this agent.

Effect of binary and ternary solid dispersions on the in vitro dissolution and in-situ rabbit intestinal absorption of gliclazide.

Solid dispersion technique is widely used to improve the dissolution rate of drugs. Most investigators relied on the in-vitro characterization and considered the enhanced dissolution as an indication of improved bioavailability. The current study investigated the effects of binary and ternary solid dispersions of gliclazide with polyethylene glycol 6000 (PEG 6000) and/or pluronic F68 (PL F68) on the dissolution of gliclazide. The study also investigated the intestinal absorption in presence of solid dispersion components. The latter employed the in-situ rabbit intestinal perfusion technique. Preparation of binary solid dispersion with PEG 6000 or PL F68 significantly enhanced the dissolution rate compared to pure drug. The ternary solid dispersion of gliclazide with both polymers resulted in rapid drug dissolution with most drug being released in the first five minutes. The intestinal perfusion indicated the possibility of complete drug absorption from the small intestine. This, together with slow dissolution of pure drug suggested that the absorption of gliclazide is dissolution rate limited. The presence of PEG 6000 did not alter the intestinal absorption but PL F68 showed a trend of enhanced intestinal absorption of the drug. Ternary solid dispersion can thus provide rapid absorption due to rapid dissolution and potential increase in intestinal permeability.