Iranian Journal of Pharmaceutical Research
Volume:8 Issue: 2, Spring 2009

The aim of this study is to formulate a novel ophthalmic nanosuspension (ONS), an alternative carrier system to traditional colloidal carriers for controlled release (CR) of acyclovir (ACV). In the present study, ONS is employed to avoid some of major disadvantages of colloidal carriers systems such as instability in cul de sac and short half life by increasing efficiency of drug encapsulation as well as by CR. A quassi-emulsion solvent evaporation method was used to prepare ACV loaded Eudragit RS 100 ONS with the aim of improved ocular bioavailability and distribution. Five different formulations were prepared and evaluated for pH of ONS, particle size, entrapment efficiency, differential scanning calorimetry (DSC), in vitro release profile, in vivo release studies and stability studies. An average size range of 100 to 300 nm in diameter was obtained and encapsulation efficiency up to 95.0% was observed for all the formulations. Cumulative percent drug released for all formulations after 24 h was between 79.28 to 95% indicating effective CR property of ONS. The release profile revealed from best formulation followed Non-Fickian diffusion mechanism. In vivo studies showed that ACV concentration in aqueous humor at 8 h was 82.83, 77.49 and 34.15 mg/ml. Stability studies showed a maximum drug content and almost similar in vitro release compared to the initial data found for the sample stored at 4°C. Overall, the study also revealed that ONS was capable of releasing the drug for a prolonged period of time and increased bioavailability.

Implantable contraceptive is likely to be a promising new option for fertility control, as we have entered the twenty-first century and the world’s population grows by one billion people in a single decade. The main objective of this study was to develop a subdermal implant for levonorgestrol (a synthetic progestin from 19-norandrostanes) using a high molecular weight biodegradable polymer, i.e. poly L-lactide (PLA), to combine the advantages of both biodegradable systems (i.e. no need to surgery for the removal of the system after the drug delivery period) and non-biodegradable reservoirs (zero order release kinetics). The implants were fabricated using a simple dip casting method. Results demonstrated that the drug release profile could be completely controlled by factors such as implant body weight, presence or absence of polyethylene glycol (PEG) in the formulation, the molecular weight of the added PEGs and their amounts, presence of osmotically active agents inside the implant, and finally the amount of loaded levonorgestrel. A constant release of levonorgestrel for at least 9 months was achieved.

This study was performed to explore the presence of heavy metals in some popular herbal medicines of the Iranian market. Primarily, this study was planned to do the task by the USP method. In the second step, those plants which contained more than 10 ppm of total heavy metals were analyzed by atomic absorption method. In this study, 43 popular herbal medicines were investigated according to the limit test procedure in the USP. It was found that 27 of these plants contained less than 10 ppm heavy metals compared to a standard lead solution, while 16 contained more than 10 ppm. The presence of Pb (<2.5), Cd (<0.25), Co (<1) and Ni (<1.5) could be considered safe.

Sesamol is a sesame lignan. Sesame lignans have multiple functions, including antioxidant activity and also seem to have potential as a source of phytostrogens. This study was condncted to evaluate sesamol contents of 7 brands of Iranian sesame seeds (sesamum indicume L.). The brands were named Karaj 29, Darab 14, Ultan, Dezful, Varamin, Branching Naz, and Nonbranching Naz. After method validation, the methanolic extracts of seeds were investigated by HPLC. Their mean of total sesamol was found to be 4.67±0.92 mg/g (ranging between 2.75 and 6.13 mg/g). The brands Karaj 29 with 5.84±0.25 mg/g, Dezful with 5.48±0.08 mg/g, and Varamin with 5.4±0.1mg/g had the highest content, and Darab 14 with the content of 3.30±0.57mg/g had the lowest (p<0.05). Iranian sesame can be considered to be a good source of natural antioxidants for medicinal and commercial uses.

Pseudomonas aeruginosa is an important opportunistic pathogen causing widespread infections by numerous virulence factors. Increasing resistance to antibiotics makes the Pseudomonas infections treatment further difficult. The purpose of this study was to evaluate antimicrobial characteristics of essential oils from Matricaria chamomilla, Artemisia persica, Zataria multiflora, Myrtus communis, Ruta graveolens, Eucalyptus camaldulensis and Ferula gummosa on Pseudomonas aeruginosa (ATCC 27853).The selected essential oils were screened against P. aeruginosa using the disc diffusion method. The minimal inhibitory and bactericidal concentrations (MIC and MBC) of the active essential oils were tested using macrodilution method at concentrations ranging from 0.125 to 256 μg/ml. It was found by GC/MS analyses that Z. multiflora, M. communis and E. camaldulensis possess the most potent oils.Three of the seven essential oils (Z. multiflora, M. communis and E. camaldulensis) were significantly active against P. aeruginosa exhibiting MIC/MBC of 64/128, 64/64 and 64/128 µg/ml, respectively. Gas chromatography mass spectrometry (GC/MS) analysis led to identification of 32, 21 and 22 components in M. communis, E. camaldulensis and Z. multiflora oils, respectively.With a view to antibacterial activity of some oils against the tested bacterium, their safe antibacterial potentials can therefore be exploited as alternative agents in combating infections of P. aeruginosa origin.

Diabetes mellitus is one of the most common endocrine diseases and its type II is the major form of diabetes, accounting for 90% of cases worldwide. The inhibition of carbohydrate hydrolyzing enzymes such as α-amylase can be an important strategy in the control of blood glucose levels in patients with type II diabetes. In this investigation, three Morus species, M. alba, M. alba var. nigra and M. nigra, were studied for their possible effects on the starch breakdown by α-amylase in vitro. M. alba var. nigra [IC50=13.26 (12.86-13.66) mg/ml] and M. alba [IC50=17.60 (17.39-17.80) mg/ml] revealed appreciable α-amylase inhibitory activities in a concentration-dependent manner. Furthermore, the most active extract (i.e. M. alba var. nigra,) was partitioned by stepwise solvent-solvent extraction process and the inhibitory activities of each of the fractions on the enzyme were studied. According to the results, all the fractions (n-hexane, chloroform, ethyl acetate and aqueous fractions) had potent inhibitory effects on the α-amylase activity. However, the lowest inhibitory potency was observed for the aqueous fraction.

In this study, effects of Buthus eupeus venom on chick biventer cervices nerve-muscle preparation were investigated by twitch tension method. The venom, at 1.3 μg/ml, increased contractile responses in indirect stimulations. These effects were milder in direct muscle stimulations. It also caused significant enhancement in postjunctional sensitivity as assessed by responses to exogenous acetylcholine, carbacole and potassium chloride. These results indicate that B. eupeus venom can cause irreversible facilitation of neuromuscular transmission by affecting postjunctional excitability in both nicotinic receptors and ion channels of the muscle cells membrane.

Indirect evidence suggests that estrogen is involved in the etiology of breast cancer. Estrogen is also thought to modulate nitric oxide (NO) in human breast tumor tissue via regulation of inducible nitric oxide synthase (iNOS). Objectives of this study were to determine whether estradiol (E2) affects iNOS expression level in breast cancer cells and to study the effect of various concentrations of E2 on cell proliferation. Immunocytochemical technique was employed to assess iNOS expression level. Proliferation of parent and 10-6 M tamoxifen resistant cells (T47D/TAMR-6) were assessed by MTT assay in the presence of E2. Addition of E2 (10-12 to 10-8 M) increases the expression of iNOS in parent cells, but not T47D/TAMR-6, Further increase in concentrations of E2 (10-8 to 10-4 M) again decreases the expression of iNOS in parent cells, but increase that of the T47D/TAMR-6 cells. Expression of iNOS in parent cells in a medium containing 1% serum (low serum) is less than the cells grown in a medium containing 10% FBS (normal serum). This trend was not seen in T47D/TAMR-6 cells. The results of these experiments may indicate that increasing of iNOS expression decreases the viability of parent cells whilst increasing the number of T47D/TAMR-6.

This study was performed to assess the clopidogrel activity in inhibition of platelet aggregation in suspected angina patients on a daily dosag of 75 mg of clopidogrel for at least 7 days. This clinical trial was conducted in the outpatients department of Cardiology, Post graduate Medical Institute, Lady Reading Hospital, Peshawar from 15th October 2007 to 20th December 2007. We included 105 suspected angina patients and measured their platelet aggregation using the WBA aggregometer provided by the sponsoring pharmaceutical company. these patient were then given seven 75 mg clopidogrel tablets for one week for a once daily regimen and were asked to come for follow up after one week. Of 133 patients, 105 completed the follow up process and platelet aggregation were measured. Both readings were noted on specially designed farms prepared in accordance with the objective of the study. Patients who were on any other anti-platelet like aspirin warfarine, heparin, etc were excluded from the study. A total of 105 patients with 28 males (52.83%) and 25 females (47.16%) were included in the study. According to age, the patients were in the range of 35 to 75 years with mean agebeing 55.79+8.74 years. Mean systolic blood pressure was 136.61+18.24 mmHg and mean diastolic blood pressure was 87.80+11.26 mmHg. Standard error of sampling for type A and type B drugs were 0.128 and 0.120, respectively. the platelet aggregation readings after follow up were zero in 73 patients (69.52%), 1-3 ohms in 26 (24.76%), and 4-6 ohms in 6 (5.71%). As a whole, clopidogrel reduced the platelet aggregation readings to below 3 ohms in 99/105 (94.28%), while in 6 (5.71%), there was some expected resistance to clopidogrel, and readings above 3 ohms were recorded. Clopidogrel has a major role in inhibition of platelet aggregation in patients with CAD. But, the activity of clopidogrel and the dose required to inhibit platelet aggregation may depend upon the individuals. Resistance to clopidogrel, especially in low doses, is expected