过氧苯甲酰乳膏稳定性研究

目的：考察过氧苯甲酰乳膏在同存过程中的稳定性。采用经典恒温加速法,利用紫外伤发光的二阶导数光谱法。不经分离直接测定乳膏中过氧苯甲酰的含量。结果：光线对该制剂的稳定性无影响;在4℃放置30日,含量降低了10%。结论：该制剂宜在冰箱中贮存,期限为30日。     

Formulation and Characterization of Benzoyl Peroxide Gellified Emulsions

The present investigation was carried out with the objective of formulating a gellified emulsion of benzoyl peroxide, an anti-acne agent. The formulations were prepared using four different vegetable oils, viz. almond oil, jojoba oil, sesame oil, and wheat germ oil, owing to their emollient properties. The idea was to overcome the skin irritation and dryness caused by benzoyl peroxide, making the formulation more tolerable. The gellified emulsions were characterized for their homogeneity, rheology, spreadability, drug content, and stability. In vitro permeation studies were performed to check the drug permeation through rat skin. The formulations were evaluated for their antimicrobial activity, as well as their acute skin irritation potential. The results were compared with those obtained for the marketed formulation. Later, the histopathological examination of the skin treated with various formulations was carried out. Formulation F3 was found to have caused a very mild dysplastic change to the epidermis. On the other hand, the marketed formulation led to the greatest dysplastic change. Hence, it was concluded that formulation F3, containing sesame oil (6%w/w), was the optimized formulation. It exhibited the maximum drug release and anti-microbial activity, in addition to the least skin irritation potential.     

Benzoyl Peroxide Solubility and Stability in Hydric Solvents

Saturated solubility and reaction rate constants for the decomposition of benzoyl peroxide in solution and suspension were determined for use in formulation development. The solvents studied included ethanol, propylene glycol, and cosolvent mixtures of PEG 400 and water. The solubility of benzoyl peroxide was inversely related to the solvent polarity, with greater solubility occurring with semipolar solvents. The stability of benzoyl peroxide in solution was dependent on the solvent, concentration of benzoyl peroxide, and temperature. The compound was least stable in PEG 400. Stability was improved when water was added to PEG 400. Similar solvent effects were observed in suspension. In benzoyl peroxide suspensions of PEG 400 and PEG 400/water blends, benzoyl peroxide stability was dependent on solubility, with improved stability occurring in blends where the benzoyl peroxide was least soluble. Thus, solution formulations of benzoyl peroxide in pharmaceutically acceptable solvents are unlikely to show good stability; however, suspension formulations should be reasonably stable if the vehicle is selected to provide low benzoyl peroxide solubility.     

Stability of Benzoyl Peroxide in Aromatic Ester-Containing Topical Formulations

The chemical stability of benzoyl peroxide (BPO) was studied in solutions and gels. The solutions (1% w/v) were prepared in single solvents (alcohol USP, isopropyl alcohol USP, ethyl benzoate, C_12–15 alkyl benzoate, dimethyl isosorbide, propylene carbonate, and acetone) and in binary and tertiary combinations of these solvents, with and without the addition of antioxidant(s) (BHT, BHA, eugenol, tert-butyl hydroquinone, Tenox-2?, vitamin E, and vitamin C). The solutions were stored at 37°C for 5 weeks, and each week were analyzed for remaining BPO. Using first-order kinetics, the stability of BPO in solution was found to decrease in the order: ternary >binary >single solvent systems. Regardless of the number of solvents present, the highest stability of BPO (t_1/2 >7.5 weeks) was attained in the presence of ethyl benzoate and C_12–15 alkyl benzoate. The stability of BPO in solution did not change significantly with the addition of most antioxidants. The solutions in which BPO remained most stable were one in alcohol USP-ethyl benzoate-C_12–15 alkyl benzoate (60:20:20; t_1/2 = 18.15 weeks) and another in alcohol USP-C_12–15 alkyl benzoate-isopropanol plus 0.1% BHT (65:20:15; t_1/2 = 12.44 weeks). In turn, these two solutions were converted to homogeneous gels by the addition of Cab-O-Sil?. The chemical stability of BPO in these gels was evaluated at 37°, 45°, 50°, and 55°C for 5 weeks. Parallel experiments were conducted with two commercial BPO products, a 2.5% tinted gel and 5% vanishing lotion. BPO was less stable in commercial products (t_1/2 ≤ 13 weeks) than in the extemporaneously prepared gels (mean t_1/2 ～23 weeks). The present results suggest that aromatic esters can enhance the chemical stability of BPO in solutions and gel formulations to a significant extent.     

The Topical Delivery of Benzoyl Peroxide Using Elegant Dynamic Hydrofluoroalkane Foams

Formulating benzoyl peroxide (BPO) in an effective topical product is challenging due to its poor water solubility and chemical instability, but delivering BPO using elegant foams is an attractive solution to this problem. The aim of this work was to investigate how nanoparticle properties influence BPO release and permeation when administrated using dynamic hydrofluoroalkane foams. Lipid (LN, ～50 nm) and polymeric (PN, ～350 nm) nanoparticles were produced and loaded into topical foams. Drug release and permeation was measured using ultrafiltration and Franz cells studies, respectively. No BPO release was detected when the nanoparticles were stored in the aqueous solvent, but upon administration to silicone membrane the pluronic surfactant‐induced LN swelling and BPO delivery (35.7 ± 3.8 µg cm^?2 h^?1). In the same situation the PN aggregated with a delivery rate of 2.5 ± 0.2 µg cm^?2 h^?1. Surprisingly the aqueous nanosuspensions delivered BPO at an equivalent rate to the foams despite the poor drug solubility in the dispersing medium presumably due to ultra‐rapid BPO solubilization kinetics of the drug in water. The delivery of BPO from the foams (0.1% BPO) was superior compared to the commercial products (5% BPO), but further testing in human skin is required prior to clinical use. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1384–1398, 2010     

An old drug with a new future: bendamustine in multiple myeloma

Although levodopa remains the gold standard treatment for Parkinson’s disease, many patients develop motor complications with chronic levodopa exposure. Tolcapone is a catechol-O-methyltransferase inhibitor that extends the action of levodopa. When used in conjunction with levodopa, tolcapone has been shown to be effective in improving motor fluctuations and reducing levodopa requirements in Parkinson’s disease patients. However, rare reports of severe hepatotoxicity have limited its use. A recent review of the data on tolcapone-treated patients suggests that, with proper monitoring of liver function, the potential for hepatotoxicity with tolcapone use is negligibly small.     

正交试验法优选过氧苯甲酰凝胶处方

目的 优选过氧苯甲酰凝胶的处方。方法 以正交试验设计，通过不同条件的实验观察、比较，筛选稳定的处方组成，用硫代硫酸钠滴定法测定过氧苯甲酰的含量。结果 最优组方为甘油12.5 g，乙醇18.75 mL，EDTA 2Na0.012 5 g，水杨酸甲酯0.125 g。所得凝胶呈白色乳状粘稠体，稳定性好，且含量测定简单易行。结论 该凝胶剂配方合理，制剂性质稳定，质量易控，适宜痤疮的治疗。     

丹参酮胶囊联合5%过氧苯甲酰凝胶治疗寻常型痤疮的疗效观察

目的:观察丹参酮胶囊联合5%过氧苯甲酰凝胶治疗寻常型痤疮的疗效与安全性。方法:将84例寻常型痤疮患者根据就诊次序随机均分为治疗组和对照组。治疗组口服丹参酮胶囊,每次4粒,tid,同时外用5%过氧苯甲酰凝胶,每日早、晚各1次;对照组仅外用5%过氧苯甲酰凝胶,每日早、晚各1次。2组疗程均为6周。结果:治疗组和对照组有效率分别为92.8%和71.4%,2组比较有显著性差异(P<0.01)。2组不良反应均较轻微,组间比较差异无统计学意义(P>0.05)。结论:丹参酮胶囊联合5%过氧苯甲酰凝胶治疗寻常型痤疮疗效显著,未见明显不良反应。     

Metformin: an old drug with new potential

Metformin is the most commonly prescribed antidiabetic oral agent. It has also been used off-label for polycystic ovarian syndrome, steatohepatitis, and HIV-associated metabolic abnormalities. However, this oldie is a newbie for the oncologist. Population studies have suggested that metformin decreased the incidence and mortality rates of cancer in diabetic patients. With better understanding of its mechanisms of antitumor activity, metformin may become a new drug for cancer in combination with chemotherapy or targeted therapy.     

AZT: an old drug with new perspectives

The science of antiviral research was well advanced when HIV/AIDS appeared as a major new virus disease in the early 1980s. The first effective antiviral compound (AZT, azidothymidine, zidovudine) was already among the library of compounds screened and was promptly reported to be a specific inhibitor of retroviruses, including HIV. Due to the pivotal role of AZT in HIV treatment, this review summarizes the most known effects -some of which are toxic side effects- induced by AZT a drug which is still used in the combined therapy of HIV-infected patients. Among the toxic side effects, a severe bone marrow toxicity manifested as anemia, neutropenia and siderosis, and caused by inhibition of heme and globin synthesis together with a general derangement of iron supply, have been reported. In this regard, we proved that while AZT and its monophosphorylated derivative AZTMP were unable to chelate iron, the triphosphate form AZTTP displayed a significant capacity to remove iron from transferrin. Moreover, we have previously demonstrated that AZT-exposed K562 cells showed an increase of transferrin receptors located on the cell membrane without affecting their biosynthesis, but slowing down their endocytotic pathway. Interestingly, literature data report the impairement of glycosylation reactions by AZT. Indeed, we have shown that AZT-treated K562 cells exhibited a reduced sialylation of proteins and lipids, and a strong inhibition of alpha,(2-->8) sialyltransferase activity while beta,(1-->4)galactosyltransferase and beta-galactosidase activities were significantly increased. These latter observations could be of clinical relevance since alterations of intracellular and cell surface carbohydrate expression and composition, often are associated with several diseases. However, contrarily to previous reports by other authors on AZT as an inhibitor of plant and bacterial toxins activity, we have demonstrated that AZT not only did not inhibit saporin toxicity, but even increased the cytotoxic activity of this plant toxin on K562 cells. Furthermore, the review enlightens the potential utilization of AZT as a tool in proteomics since in the recent years several genes responding to this drug have been identified in different cell lines. We have shown, for the first time, an over-expression of two proteins (PDI-A3 and sthatmin), and a full repression of two others (HSP-60 and SOD1) in AZT-exposed K562 cells. At present, we are investigating if the above reported alterations are a general feature of AZT-treatment of cultured cells, or they represent a peculiar characteristic of a specific cell line. Finally, the paper reviews a number of novel methodologies aimed at enhancing the AZT plasma levels and its bioavailability in all human organs in order to improve its therapeutic efficacy against HIV infection. These new possibilities, namely the AZT prodrug strategy, the AZT transdermal delivery and the targeted brain delivery, are yet not in use for humans but they are under experimental studies.     

An old drug with a new purpose: cardiovascular actions of acetaminophen (paracetamol)

For over 50 years, acetaminophen (paracetamol) has been a staple in industrialized and non-industrialized countries for the treatment of pain and fever. Although its precise mechanisms of action are not known, the drug generates dose-dependent reduction in circulating prostaglandins, inhibits myeloperoxidase and the oxidation of lipoproteins, and appears to confer cardioprotection by blocking the effects of hydroxyl radical, peroxynitrite, and hydrogen peroxide. The drug might inhibit cyclooxygenase, although its ultimate target(s) is (are) still unclear. Sadly, since most investigations of acetaminophen have focused on its analgesic/antipyretic properties and hepatotoxicity, the effects of the drug on other mammalian organ systems, including the heart and circulation, have been ignored. Recently, work in our laboratory has shown acetaminophen to have a protective role in the injured mammalian myocardium. The cardioprotection was first observed in isolated, perfused guinea pig hearts subjected to ischemia-reperfusion injury. Hearts pretreated with acetaminophen recovered greater ventricular function and exhibited improved myofibrillar ultrastructure when compared to vehicle-treated hearts. More recent in vitro investigations have suggested protective roles for acetaminophen in barbiturate-induced arrhythmogenesis and myocardial hypoxia-reoxygenation injury. We have also extended our work to the in vivo arena. There, we found that acetaminophen reduced infarct size in dogs exposed to 60 minutes regional myocardial ischemia and 180 minutes reperfusion. We invite and encourage readers of this review to repeat/duplicate our experiments. Such work is needed to either challenge or support our findings. Further, more clinically-relevant work depends on these basic and related translational experiments.     

Paracetamol – An old drug with new mechanisms of action

Paracetamol (acetaminophen) is the most commonly used over‐the‐counter (OTC) drug in the world. Despite its popularity and use for many years, the safety of its application and its mechanism of action are still unclear. Currently, it is believed that paracetamol is a multidirectional drug and at least several metabolic pathways are involved in its analgesic and antipyretic action. The mechanism of paracetamol action consists in inhibition of cyclooxygenases (COX‐1, COX‐2, and COX‐3) and involvement in the endocannabinoid system and serotonergic pathways. Additionally, paracetamol influences transient receptor potential (TRP) channels and voltage‐gated Kv7 potassium channels and inhibits T‐type Cav3.2 calcium channels. It also exerts an impact on L‐arginine in the nitric oxide (NO) synthesis pathway. However, not all of these effects have been clearly confirmed. Therefore, the aim of our paper was to summarize the current state of knowledge of the mechanism of paracetamol action with special attention to its safety concerns.     

Thalidomide: an old drug with new clinical applications

Thalidomide has several targets and mechanisms of action: a hypnosedative effect, several immunomodulatory properties with an effect on the production of TNF-alpha and the balance between the different lymphocyte subsets and an antiangiogenic action. Thalidomide has been used in several cutaneous inflammatory disorders (e.g., erythema nodosum leprosum in lepromatous leprosy, cutaneous lupus erythematosus and severe aphtosis), cancers (e.g., relapsed/refractory multiple myeloma, malignant melanoma and systemic signs in cancer) and inflammatory conditions (e.g., Crohn's disease and rheumatoid arthritis). Several side effects are associated with thalidomide. Some are major, such as teratogenicity, peripheral neuropathy and deep vein thrombosis. Somnolence and rash are frequently reported when thalidomide is used at higher doses as an anticarcinogenic agent and can lead to dose reduction or treatment discontinuation depending on severity. Minor side effects include abdominal pain and endocrine disturbances. To prevent the teratogenicity, use of thalidomide is strictly controlled in western countries with close adherence to a birth control programme. Close monitoring for early development of peripheral neuropathy is also recommended.     

Thalidomide: an old drug with new clinical applications

Thalidomide has several targets and mechanisms of action: a hypnosedative effect, several immunomodulatory properties with an effect on the production of TNF-α and the balance between the different lymphocyte subsets and an antiangiogenic action. Thalidomide has been used in several cutaneous inflammatory disorders (e.g., erythema nodosum leprosum in lepromatous leprosy, cutaneous lupus erythematosus and severe aphtosis), cancers (e.g., relapsed/refractory multiple myeloma, malignant melanoma and systemic signs in cancer) and inflammatory conditions (e.g., Crohn’s disease and rheumatoid arthritis). Several side effects are associated with thalidomide. Some are major, such as teratogenicity, peripheral neuropathy and deep vein thrombosis. Somnolence and rash are frequently reported when thalidomide is used at higher doses as an anticarcinogenic agent and can lead to dose reduction or treatment discontinuation depending on severity. Minor side effects include abdominal pain and endocrine disturbances. To prevent the teratogenicity, use of thalidomide is strictly controlled in western countries with close adherence to a birth control programme. Close monitoring for early development of peripheral neuropathy is also recommended.