DARU, Journal of Pharmaceutical Sciences
Volume:14 Issue: 2, summer 2006

The floating microspheres have been utilized to obtain prolonged and uniform release in the stomach for development of a once daily formulation. The major advantage of the preparation technique includes short processing time, the lack of exposure of the ingredients to high temperature, and high encapsulation efficiencies. In the present study, preparation of metformin hydrochloride floating microspheres, evaluation of Floating Drug Delivery System (FDDS) in vitro, prediction of the release, and optimization of floatation and drug release pattern to match target release profile was investigated. Floating microspheres were prepared by non-aqueous emulsification solvent evaporation technique using Ethylcellulose as the rate controlling polymer and 250 mg of metformin hydrochloride per batch and its in vitro performance was evaluated by the usual pharmacopoeial and other tests such as drug-polymer compatibility (FTIR scan), yield (%), particle size analysis, drug entrapment efficiency, surface topography, and in vitro floatation and release studies. Results showed that the mixing ratio of components in the organic phase affected the size, size distribution (250-1000 m), drug content (61 – 134% of theoretical load), yield (58 – 87%) and drug release of microspheres (47 – 87% after 8 h), floating time (> 8 hr) and the best results were obtained at the ratio of drug: polymer: solvent (250:750:12 and 250:146.45:9 [mg: mg: ml]), when both the batches were mixed in equal proportions. In most cases good in vitro floating behavior was observed and a broad variety of drug release pattern could be achieved by variation of the polymer and solvent ratio, which was optimized to match target release profile. The developed floating microspheres of metformin hydrochloride may be used in clinic for prolonged drug release in stomach for at least 8 hrs, thereby improving the bioavailability and patient compliance.

The effects of polymer molecular weight on drug release from erodible matrices are not well known. It would be more complicated for in-situ forming injectable implants that change gradually from liquid to solid after injection. To investigate this phenomenon, two commerciallyaavailable PLGA polymers (lactic acid-co-glycolic acid) with molecular weights of 12000 and 48000 Da were used to prepare injectable implants containing leuprolide acetate as a model peptide. The influence of polymer molecular weight on the morphology and erosion of matrices and also on their in-vitro drug release behavior over a period of 28 days was investigated. Results showed that the amount of drug released (32%) over the first 24 hours (burst phase) for 12 kDa PLGA system, was significantly (P<0.05) higher than that of the one higher molecular weight (13%). There was no difference between the steady-state release fluxes of drug from the systems. Erosion profiles were also in agreement with those of release behavior in both burst and steady-state phases. Electron microscopy studies showed that the lower molecular weight system is more porous than the higher one, which can explain the difference between burst effects.

The composition of hydrodistilled essential oil from aerial parts of Phlomis olivieri Benth. (Lamiaceae), were analyzed by GC and GC-MS. Twenty two constituents, representing 93.6% of the oil of P. olivieri were identified. The main compounds were germacrene D (66.1%), β- selinene (5.1%), b-caryophyllene (4.2%) and -pinene (4.2%). A comparison of the composition of this oil with other oils of P. olivieri from different regions showed that germacrene D and β- caryophyllene are main compounds of all oils.

Johreniopsis seseloides (C.A.MEY) Pimenov (Umbelliferae) was collected from Tehran and Kurdistan provinces in August 2004. The essential oil of the plant powdered aerial parts which were prepared by hydro-distillation and Clevenger type apparatus were about 0.1% and 0.15% (v/w) respectively. The oil had pale yellow color and intensive odor. The essential oils were analyzed with GC/MS. Thirty six compounds were identified from two plants, accounting 77.19% and 97.04% of the oil contents respectively. The essential oil of J.seseloides from Darake (Tehran province) contains monoterpenes (24.05%) and sesquiterpenes (43.19%). The essential oil of J.seseloides collected from Gardaneh Haris Kurdistan (Kurdistan province) contains monoterpenes (69.67%) and sesquiterpenes (26.69%). The main constituents of the essential oil of J.seseloides from Tehran were spathulenol (18.21%) and α-terpineol (7.97%), followed by hexahydro-farnesyl acetone (7.05%) and α-pinene (6.98%). Other monoterpenes and sesquiterpenes, either as hydrocarbons or oxygenated, were present in smaller amounts. The essential oil of J.seseloides from Kordestan province was found to be rich in α-pinene (26.25%), α-bornyl acetate (12.36%), limonene (10.32%), α-fenchyl acetate (9.06%) and β-caryophyllene (8.58%). The essential oil of other species of Johreniopsis has not been investigated up to now and this is the first report about essential oil components of J.seseloides.

Infection with human papiloma virus (HPV) is the most frequent sexually transmitted disease worldwide. HPV types 16, 18, 31 and 33 are considered as the most important types in the cervical cancer.This study was undertaken on 64 samples of archival cervical carcinoma pathologic to assess the rate of HPV infection (HPV16,18) in cervical carcinoma among Iranian patients. HPV DNA was detected by polymerase chain reaction (PCR) and typing by restriction fragment length polymorphism (RFLP) analysis.The total prevalence of HPV in this study (HPV16,18) for all cases was 59.4% (38/64). HPV type 16 was the most common one (22/64, 34%) followed by HPV type 18 (16/64, 25%). On the basis of the rate of HPV (16,18) which were detected in squamous cell carcinoma and adenocarcinoma,only women with HPV18 infection showed a statistically significant risk for development of cervical cancer (P=0.019) while P value for HPV16 was 0.47.

Renin angiotensin system (RAS) has an important role in the regulation of hypertension. RAS includes angiotensinogen, Angiotensin Converting Enzyme (ACE), angiotensine II and angiotensin receptors (AGTR). Angiotensin receptors have several types but AT1R is the main subtype. In this study the effect of A1166→C polymorphism of AT1R gene and the role of possible genetic differences in hypertension was investigated. DNA of the whole blood leukocytes from hypertensive patients and healthy people of Mashhad population as control, were extracted and then PCR was performed on prepared samples followed by amplification of the target fragments which were then digested with the DdeI restriction enzyme. Data were classified on the basis of genotypes and gender and then alleles and genotypes frequencies were analyzed statistically. There were no significant differences in the genotype, and allele frequencies between hypertensive and normotensive subjects. However, frequency of C allele of AT1R gene in hypertensive women was significantly higher than normotensive women (P<0.05). These results suggest that C allele of AT1R gene may be an important risk factor for essential hypertension in women.

A checkerboard broth microdilution method was performed to investigate the in vitro antifungal activities of three diazeniumdiolates derivatives (DETA/NO, DPTA/NO, DEA/NO) alone and in combination with ketoconazole, amphotricin B or terbinafine against five Candida species, Cryptococcus neoformance and four dermatophyte strains. MICs and MLCs were recorded, and synergy was calculated by using fractional inhibitory and fractional lethal concentration index. DETA/NO with a half-life of 57h at 25°C showed antifungal activity against all tested dermatophyte species (MIC 0.150 to 2.5mg/ml), DPTA/NO with a half life of 3h at 37°C showed antifungal activity against five species of Candida and Cryptococcus neoformans, and DEA/NO with a half life of 2 min at 37°C and 16 min at 25°C did not show antifungal activity against tested strains. Combinations of DPTA-NO with either ketoconazole or amphotericin B were either synergistic or indifferent for all tested strain of Candida and Cryptococcus neoformance. DETA/NO was unable to enhance the antifungal activity of terbinafine against dermatophyte strains. Even where no synergistic activity was achieved, there was still a decrease in the MIC of one or both drugs which were used in combination. Antagonism was observed between terbinafine and DETA-NO against Trichophyton rubrum. Our result suggests that DETA/NO and DPTA/NO may be useful for development of new therapeutic strategies for treatment of dermatophyte and Candida infections. Clinical studies are warranted to elucidate the potential utility of these combination therapies.

This study was designed to compare the influence of ordinary (multiple-dose) and once-daily administration of gentamicin on tubular nephrotoxicity based on the urinary excretion of magnesium (Mg) as an indicator for this type of side effect. Thirty-two hospitalized patients, who were assigned to receive at least 5-days treatment with gentamicin at the infectious disease ward of Imam Hospital in Tehran, were prospectively studied. Seventeen patients received multiple-doses of gentamicin per day and 15 patients received once-daily regimen. At the beginning and at the end of of gentamicin therapy, blood urea, serum creatinine (Cr) and Mg levels were measured. Additionally 24-hour urine samples were collected for measurement of urinary volume, creatinine and Mg excretions. In both treatment groups serum Mg concentration was significantly lower and fraction excretion of (FEMg) were considerably higher at the end of gentamicin therapy compared with the beginning of the treatment. However, the serum and urinary creatinine levels did not change significantly in the two groups

inger (rhizome of Zingiber officinale Roscoe) is a widespread herbal medicine mainly used for the treatment of gastrointestinal (GI) disorders including: dyspepsia, nausea and diarrhea. Aromatic, spasmolytic, carminative and absorbent properties of ginger suggest that it has direct effects on the GI tract and anti-ulcerogenic potential. In the present study, the effects of this herbal remedy on an acute model of experimental duodenal ulcer induced by cysteamine was evaluated. Hydroalcoholic extract ofgginger with doses of 100, 350, 700 mg/kg, ranitidine (50 mg/kg), sucralfate (500 mg/kg) and 5 ml/kg of vehicle were administered orally (p.o.) to separate groups of male Wistar rats. Other groups received vehicle (5 ml/kg), extract (300 mg/kg) and ranitidine (50 mg/kg) intraperitoneally (i.p.). After ulcer induction, the number, scoring, area and finally ulcer index were assessed for each duodenum. Administration of extract by i.p. or at chronic doses (350 mg/kg) and ranitidine (p.o. and i.p.) resulted in significant reduction in mucosal damage for the entire ulcer factors which were assessed. Larger doses of extract given p.o. (350 and 700 mg/kg) were effective to reduce both the ulcer area and index but the lowest dose of extract (100 mg/kg) was not effective. Taken together, we conclude that ginger hydroalcoholic extract was effective to protect against duodenal ulceration and for i.p. injection as well as chronic administration, the efficacy was comparable with ranitidine as reference drug.

Single-pass intestinal perfusion technique (SPIP) is the most used classic technique employed in the study of intestinal absorption of compounds in which a non-absorbable marker such as phenol red is used to correct the water flux. A simple and rapid reversed-phase high performance liquid chromatographic method with UV detection at 227 nm was developed for simultaneous quantitation of propranolol and metoprolol along with phenol red for in-situ permeability studies. The mobile phase was a mixture of 55% methanol, 45% of 0.05 M KH2PO4 aqueous solution (adjusted to pH 6) and 0.2 % (v/v) triethylamine. Analysis was run at a flow rate of 1 ml/min with a 9 min run time. The calibration curves were linear for all three compounds (r > 0.999) across the concentration range of 7.5-125 μg/ml with a limit of detection of 4.24, 2.18 and 8.57 ng/ml and limit of quantification of 14, 7.2 and 28.3 ng/ml for metoprolol, propranolol and phenol red respectively. The coefficient of variation for intra-assay and inter-assay precision was less than 8% and the accuracy was between 93.6-107%. Using the SPIP technique and the suggested HPLC method for sample analysis, the mean values of 0.49 e-4 (±0.19) cm/sec and 0.32 e-4 (± 0.09) cm/sec were obtained for propranolol and metoprolol intestinal permeability coefficients respectively.