Iranian Journal of Pharmaceutical Sciences
Volume:1 Issue: 3, Summer 2005

In this work we sought to determine whether vesicles (liposomes/niosomes) were able to enhance finasteride concentration in the dermis layer, including the pilosebaceous units (PSU). Such enhancement could be beneficial in the treatment of some androgen-related skin disorders. Hamster flank skin was used to study  3Hfinasteride permeation via vesicles and a hydroalcoholic solution (HA). The drug-containing vesicles were composed of dimyristoyl phosphatidylcholine (DMPC) or egg lecithin: cholesterol: dicetyl phosphate (liposomes) and polyoxyethylene  alkyl ethers (Brij ® series) or sorbitan monopalmitate (Span 40): cholesterol: dicetyl phosphate (niosomes) and were prepared by the film hydration technique. Determination of finasteride content by HPLC showed 80-97% drug entrapment efficiency in the vesicles. The amount of 3H-finasteride penetrated into and permeated through hamster skin 24 h after topical application of vesicles ranged from 5.5 to 13% of the initial dose, compared to 24%, observed with HA  ( pSpan 40 and lecithin vesicles was lower, when compared with liquid-state Brij97, Brij 76: Brij 97 and DMPC vesicles. The fraction of finasteride found in the dermis  layer was greatest where DMPC liposomes were used (7.8%). The vesicles significantly reduced drug permeation as indicated by the flux of finasteride from vesicles (0.025-0.058 µg/cm 2.h), where compared with the HA (0.13 µg/cm2.h),  (pthe percutaneous absorption of finasteride and increasing its concentration and retention in the dermis layer.

Benzoyl peroxide (BPO) is a first-line topical treatment in acne vulgaris, and it is superior to antibiotics, because the bacteria do not develop resistance to it. Skin irritation is a common side effect, and it has been shown that controlled release of BPO from a delivery system to the skin could reduce the side effects while reducing percutaneous absorption. Therefore, the purpose of the present investigation was to prepare suitable controlled release formulations for BPO. This study examined whether the type of topical formulation (cream, gel and lotion) can affect the release behavior of BPO from microsponges. Benzoyl peroxide microparticles were prepared using an emulsion solvent diffusion method by adding an organic internal phase containing benzoyl peroxide, ethyl cellulose and dichloromethane into a stirring aqueous phase containing polyvinyl alcohol. The loading capacity of the drug content and the mean particle size of microparticles were determined. BPO microparticles were then incorporated into various formulations (creams, gels and lotions) for release studies. The micrograph of microsponges showed that they were spherical in shape and contained pores. It was shown that the drug:polymer ratio, stirring rate, volume of the dispersed phase influenced the particle size and drug release behavior of the formed microsponges and that the presence of emulsifier was essential for microsponge formation. The results showed that, generally, an increase in the ratio of drug:polymer resulted in a reduction in the release rate of BPO from microsponges which was attributed to a decrease in internal porosity of the microsponges. The release data showed that the highest release rate was obtained from lotions containing BPO microparticles and the lowest was obtained from cream formulations.

The purpose of this study was to prepare and characterize nimodipine loaded microspheres using ethyl cellulose (EC) as a carrier polymer through an emulsion solvent evaporation method. These evaluations characterized the pattern of drug release from prepared microspheres. Nimodipin loaded microspheres were prepared using an emulsification solvent evaporation method. The effect of process variables such as stirring rate, drug polymer ratio in the organic phase, the viscosity of the dispersed phase and the emulsifier concentration, on the morphology of microspheres, particle size distribution, drug content and in vitro release profile of nimodipine were investigated. The prepared microspheres were spherical with smooth surface. The mean diameter of microspheres decreased with increasing the concentration of the emulsifier in the continuous phase and stirring rate of the medium. However, increasing the viscosity of the dispersed organic phase increased the particle size of microspheres. Both the drug and polymer concentration in the organic phase increased the entrapment of nimodipine in ethyl cellulose microspheres. Drug content of the microspheres was lowered by increasing the viscosity of the dispersed phase and increasing the concentration of poly vinyl alcohol. The rate of drug release from microspheres was directly influenced by the drug to polymer ratio, as any increase in this ratio allowed the higher release rates from microspheres. The higher  the polymer concentration the lower was the rate of drug release from microspheres.

Superoxide dismutase (SOD) is an important antioxidant that protects many types of cells from the free radical damage. One of the possible ways for the use of SOD is its incorporation in liposomes. The aim of this study was to investigate the effect of cationic phospholipids on the entrapment of human erythrocyte superoxide dismutase (Cu/Zn SOD) in liposomes. Also, in the present study, we examined the effect of this formulation on the permeability of these liposomes for SOD at two different temperatures (4 °C and 37 °C). Cu/Zn SOD was purified from human erythrocytes. Several methods, including, precipitation by acetone, chloroform, centrifugation and also ion exchange chromatography on DEAE-32 were applied. In this study, encapsulated SOD in liposomes was prepared using the film hydration method. The results obtained from the prepared human erythrocyte SOD showed that at the end of the last stage, the purification was 21 times the result of the first stage, with a specific activity of 3000 U/mg. The enzyme activity and the retained enzymatic activity in liposome solution were 74±0.2 U/mg and 45%, respectively. Incubation of SOD-liposomes at 4 °C and 37 °C for 8 hours, caused the enzyme activity to decrease to 66±0.2 U/mg and 31±0.2 U/mg, respectively. The present study showed that preparation of the liposomes with cationic phospholipids was an important role in the increase of the entrapped enzyme.

Three major flavonoid fractions were separated from a methanol extract of Calendula officinalis flowers by preparative TLC. These fractions were evaluated for the inhibition of parent and tamoxifen resistant T47D human breast cancer cells. We also examined the effect of quercetin and isorhamnetin on the growth of parent and resistant T47D cells in the presence and absence of tamoxifen. It was found that quercetin increased cell proliferation of the resistant T47D cells at the presence of tamoxifen but no effect was detected by using quercitin alone. The fractions isolated from  Calendula officinalis did not show any inhibitory effects on the cells. Isorhamnetin did not have any proliferative or anti-proliferative activity on the both cell lines.

The composition of the essential oils of two African (“white” and “yellow”) olibanums available in the commercial market of Isfahan (Iran) was analyzed by gas chromatography (GC) and GC-mass spectroscopy methods. The main constituents of the “White” olibanum oil were alpha-pinene (34.8%), limonene (15.9%), alphathujene (9.0%), para-cymene (7.0%), myrcene (6.2%) and sabinene (6.0%). Major components of the “yellow” olibanum oil were alpha-pinene (48.0%), limonene (21.7%), myrcene (4.9%),beta-caryophyllene (4.9%) and para-cymene (3.5%).

The binding of drugs by plasma proteins is an important phenomenon, because it influences the size of the free fraction of the drugs in plasma. In this study the influence of dipyridamole (DP) on the protein binding of propranolol (PL) and PL on the protein binding of DP were studied alone and in the presence of nicotine (NC).        The equilibrium dialysis was employed for protein binding studies. Results showed that DP (10 μg/ml) increased the protein binding of PL (1-40 μg/ml) by 4.1%, and PL(30 μg/ml) decreased the protein binding of DP (1-30 μg/ml) by 3.7%. NC (2 μg/ml) did not have any influence on the protein binding of PL and DP. Therefore, coadministration of PL and DP may cause an alteration in their pharmacological effects, but cigarette smoking possibly does not change protein binding of PL and DP.

The administration of b-interferon is a recognized treatment for multiple sclerosis. The frequency of side effects is an important factor in drug or product selection. In this study, the side effects of three available b-interferon products are compared in 122 multiple sclerosis patients who were treated with b-interferon products for at least three months and had the Expanded Disability Status Scale (EDSS) between 1 and 6. The frequencies of side effects were determined for each group and the collected information were compared in the three treated groups. Fever, chills, headache, malaise and asthenia were the most frequent observed complications. Necrosis at the injection site was seen only in Betaseron group. Somnolence was more frequent with the administration of Avonex. Gastro-intestinal disturbances were less frequent in patients treated with Rebif. Weight gain was more frequent in patients treated with Avonex, and seizure and migraine were observed only in this group.Urticaria and hypersensitivity skin reactions were less frequent with the administration of Avonex. Rebif may be a better choice for patients with gastrointestinal disturbances, suicidal attempts and chronic fatigue syndrome. Avonex may be better tolerated in patients with a history of urticaria and hypersensitivity skin  reactions, but it is less recommended for patients with a history of seizure, migraine and syncope. Betaseron may be a better choice in patients with a history of chest pain and hypertension.

Apatient was admitted to the hospital because of epistaxis, ecchymoses and gum bleeding with INR of 5.5. This patient had a known case of diabetes mellitus type II, 5 years ago. The last dose of glibenclamide for managing signs and symptoms of diabetes mellitus was 20 mg/day. Her medical history also showed that last month she was diagnosed with atrial fibrillation with normal left ventricular ejection fraction (LVEF> 45%) and was placed on warfarin (5 mg) and propranolol (80 mg) daily, which resulted in resolution of atrial fibrilation, a pulse rate of 80 bps and INR of 3 (target INR=2-3). An objective causality assessment indicated the increased effect of warfarin and as a result bleeding could best be explained by drug-drug interaction because there are no other factors such as pathological evidences (e.g. thyroid disease, hepatic disorders) to prove it otherwise. This case is the third report of drug interaction between warfarin and glibenclamide, therefore, this is an interesting and educational case.      In view of our experience in the present case, it should be stressed that close monitoring of coagulation capacity is necessary in co-administration of warfarin and other drugs which can affect pharmacokinetic and pharmacodynamic of warfarin.