DARU Journal of Pharmaceutical Sciences
Year:2008 | Volume:16 | Issue:3|Papers Count:12

Purpose: Tinidazole is used in treatment of amoebiasis and other protozoal infections in doses of 2.0 g/day (60 mg/kg) for three days. In the present paper, controlled release formulation of tinidazole was developed with an objective to achieve colon specific drug delivery with reduced frequency of dosing, to minimize gastric side effects and thus to increase patient compliance. Methods: Matrix systems of tinidazole (500 mg) were prepared by using swellable and pH dependent polymers like hydroxypropyl methylcellulose (HPMC K4M and K15M) and eudragit (eudragit L-100 and S-100). Prepared tablets were enteric coated in order to overcome variability in gastric emptying time and delay in the release, to reduce gastric side effects and to provide prolonged localized action in colon. Process of manufacture was optimized during the scale up studies. Bioavailability study (using parallel group design) was carried of on conventional marketed, developed uncoated and enteric coated tablets in healthy human volunteers.Results: Bioavailability study showed that greater portion of tinidazole was released in the large intestine and drug level in plasma was above 4 mg/mL in blood for 24 hours. Conclusion: From the results of this study it appears that, the proposed single enteric coated tinidazole (500 mg) tablet per day could be used in place of 3-4 doses of 500 mg tinidazole conventional tablet with better control of drug release for targeted drug delivery. In addition developed colon-specific drug delivery system (CDDS) was relatively inexpensive and easy to manufacture using conventional pharmaceutical coating technique.

Backgrond and the purpose of the study: The aim of this study was to evaluate the effect of solvents used in the spray drying and the aerodynamic properties of the rifampicin microparticles and pulmonary absorption of the microparticles. Methods: Different mixtures of dichloromethane and water were used as solvents for spray drying of rifampicin microparticles. The water to dichloromethane ratios were 25:75, 50:50, 75:25, 80:20, 90:10 and 100:0. The solutions were dried at inlet temperature of 70oC. The powder properties of the samples were examined by laser diffraction, scanning electron microscopy (SEM), helium densitometer and infrared spectroscopy (IR). The aerosolization performance of these formulations was investigated using an Andersen cascade impactor. Pulmonary absorptions of formulations were examined by the in situ pulmonary absorption described by Enna and Schanker method. The plasma concentration time profiles of rifampicin were constructed 8 hours following the intravenous and the intrapulmonary administrations. The pharmacokinetics parameters, Cmax, Tmax, t1/2, AUC, mean residence time (MRT), Ka and Ke were determined for each formulations. Results and major conclusions: The Tmax values for the samples decreased by increase in the amount of water in the initial feed. The Tmax values for the spray dried samples from the different mixtures of dichloromethane and water were 60(min) and 30(min) respectively.The solvent mixture as the spray drying vehicle played an important role in the in vitro and in vivo lung deposition. The type of spray drying vehicle showed significant effect on the aerodynamic behavior and pharmacokinetic parameters of the particles. The pulmonary absorption of drug revealed the possibility of achieving the minimal inhibitory concentration (MIC) of the antibiotics. The spray drying vehicle only affected absorption patterns of the formulations and it did not have any effect on the elimination rat of particle.

Background and purpose of the study: Propranolol HCl, a widely used drug in the treatment of cardiac arrhythmias and hypertension, is a weak basic drug with pH-dependent solubility that may show release problems from sustained release dosage forms at higher pH of small intestine. This might decrease drug bioavailability and cause variable oral absorption. Preparation of a sustained release matrix system with a pH–independent release profile was the aim of the present study. Methods: Three types of organic acids namely tartaric, citric and fumaric acid in the concentrations of 5, 10 and 15% were added to the matrices prepared by hydroxypropyl methylcellulose (HPMC) and dicalcium phosphate. The drug release studies were carried out at pH 1.2 and pH 6.8 separately and mean dissolution time (MDT) as well as similarity factor (ƒ2) were calculated for all formulations. Results and discussion: It was found that incorporation of 5 and 10 % tartaric acid in tablet formulations with 30% HPMC resulted in a suitable pH-independent release profiles with significant higher ƒ2 values (89.9 and 87.6 respectively) compared to acid free tablet (58.03). The other two acids did not show the desirable effects. It seems that lower pKa of tartaric acid accompanied by its higher solubility were the main factors in the achievement of pH-independent release profiles.

Background: Although a number of investigation have been carried out to find alternative adjuvants to aluminum salts in vaccine formulations, they are still extensively used due to their good track record of safety, low cost and proper adjuvanticity with a variety of antigens. Adsorption of antigens onto aluminum compounds depends heavily on electrostatic forces between adjuvant and antigen. Commercial recombinant protein hepatitis B vaccines containing aluminum hydroxide as adjuvant is facing low induction of immunity in some sections of the vaccinated population. To follow the current global efforts in finding more potent hepatitis B vaccine formulation, adjuvanticity of aluminum phosphate has been compared to aluminum hydroxide. Materials and methods: The adjuvant properties of aluminum hydroxide and aluminum phosphate in a vaccine formulation containing a locally manufactured hepatitis B (HBs) surface antigen was evaluated in Balb/C mice. The formulations were administered intra peritoneally (i.p.) and the titers of antibody which was induced after 28 days were determined using ELISA technique. The geometric mean of antibody titer (GMT), seroconversion and seroprotection rates, ED50 and relative potency of different formulations were determined. Results: All the adjuvanicity markers obtained in aluminum phosphate formulation were significantly higher than aluminum hydroxide. The geometric mean of antibody titer of aluminum phosphate was approximately three folds more than aluminum hydroxide.Conclusion: Aluminum phosphate showed more adjuvanticity than aluminum hydroxide in hepatitis B vaccine. Therefore the use of aluminum phosphate as adjuvant in this vaccine may lead to higher immunity with longer duration of effects in vaccinated groups.

Background and objectives: Excoecaria agallocha L. (Family: Euphorbiaceae) is a Bangladeshi medicinal plant found predominantly in the tidal forests and swamps of the Sundarbans and other coastal areas in Bangladesh. As part of our on-going phytochemical and bioactivity studies on medicinal plants from Bangladeshi flora, the in vitro antioxidant property on the bark of this plant was evaluated. Methods: The hydroalcohol extract of the dried and ground bark of E. agallocha was assessed for antioxidant activity using a series of well-established assays including the 2,2- diphenyl-1-picrylhydrazyl (DPPH), the lipid peroxidation by thiobarbituric acid (TBA), the reducing power, the nitric oxide (NO.) and the hydrogen peroxide (H2O2) scavenging assays. Results: In the DPPH, the NO and the H2O2 scavenging assays, the extract of E. agallocha displayed significant antioxidant activities with the IC50 values of 179.16, 120.24 and 134.29 mg/ml, respectively. The reducing power of the extract increased dose-dependently, and the extract reduced the most Fe3+ ions to the extent less than butylated hydroxy toluene (BHT). In the lipid peroxidation assay, the extract showed significant inhibition of peroxidation effect at all concentrations, with an IC50 value of 189.27 mg/ml.Conclusion: Since reactive oxygen species are important contributors to serious ailments such as atherosclerosis, alcoholic liver cirrhosis and cancer, the antioxidant property of the extract of E. agallocha as observed in the present study might be useful for the development of newer and more potent antioxidants.

Background and purpose of the study: Acetaminophen is a commonly used analgesic and antipyretic agent which, in high doses, causes liver and kidney necrosis in man and animals. Curcuma longa has been reported to have anti oxidant and hepato-protective properties. In this study the protective effect of Curcuma longa extract on acetaminophen induced nephrotoxicity has been evaluated. Materials and methods: Sixty NMRI male mause were randomly divided into 6 groups. Control group received normal saline. Curcuma longa group received 1000 mg/kg of the extract of the plants, positive control group received 500 mg/kg acetaminophen. Acetaminophen and Curcuma longa extract at doses of 400, 800 and 1000 mg/kg were administered to the tested groups (T1- T3) at the same time. The jugular arteries of the mice were cut for biochemical testes after 48 hours and the kidney removed in 10% formalin solution for histopathology testes. Results: BUN, Cr and Uric acid reduced significantly in the T3 group (p<0.05). Necrosis of kidney reduced in test groups especially in T3 group. Conclusion: The results of this study indicate that Curcuma longa extract may protect kidney against acetaminophen - induced tubular necrosis in mice.

Background and the purpose of study: Hydroalcoholic extract of Pycnocycla spinosa has a relaxant effect on ileum and inhibits castor oil induced diarrhoea in mice. However, effects of P. spinosa seed extracts on ileum and uterus hasn’t been investigated. The aim of this study was to investigate effect of P. spinosa seed and extracts of the aerial part on rat ileum and uterus smooth muscle contraction. Methods: A 70% ethanol extract of seed and aerial parts of P. spinosa was prepared by a percolation method. Uterine horns or ileum were dissected from non-pregnant female Wistar rats (200-230g) and cut into longitudinal strips and mounted for isotonic recording under 1g tension in Tyrode’s solution. Effects of the extracts were examined on tonic contractions induced by KCl (80mM) on both tissues and on phasic spasm induced by oxytocin (0.002iu/ml) on the uterus. Results: The aerial part extract inhibited rat ileum contractions induced by 80mM KCl (IC50=42±3.4mg/ml) in a concentration dependent manner and it also inhibited rat uterus contraction induced by 80 mM KCl. However, its inhibitory effects were observed with higher concentration of the extract (IC50=420±90μg/ml) and at concentration of 1.28mg/ml of the extract in the bath the response was 19±7%. The aerial part extract (40-640mg/ml) also reduced the evoked phasic response of uterus by oxytocin (IC50=71±17.3mg/ml). The seed extract reduced the uterus response to oxytocin in a concentration-dependent manner, and inhibited tissue response completely at 160mg/ml (IC50=27±4mg/ml).Major conclusion: From this study it was concluded that the seed extract of P. spinosa have similar inhibitory properties on rat isolated uterus and ileum contractions, while the extract of the aerial part of P. spinosa is more selective inhibitor of ileum contraction, and at higher concentrations it also inhibits uterus spasm.

Background: Airway instrumentation in patients with bronchial hyper reactivity, may evoke life-threatening asthma attack and a good strategy for the prevention of bronchospasm has not been defined. In a randomized, prospective, placebo-controlled study, it was determined whether prophylaxis with either inhaled salbutamol-or combined inhaled salbutamol and oral methylprednisolone improves lung functions and prevents wheezing after intubation. Methods: Thirty one patients with partially reversible airway obstruction (airway resistance> 180%, forced expiratory volume in 1 second [FEV1] < 70% of predicted value, and FEV1 increase> 12% after two puffs of salbutamol) were randomized to receive daily either 3-2 puffs (0.2 mg) of salbutamol (n=16) or 3-2 puffs (0.2 mg) of salbutamol and 40 mg of methylprednisolone (n=15) orally for 5 days. In all patients lung function was evaluated daily and wheezing changes was assessed before and 5 minutes after tracheal intubation. Results: Both salbutamol and combined inhaled salbutamol and oral methylprednisolone treatment significantly improved airway resistance and FEV1 to a steady state, with no difference between groups. When a single-dose of salbutamol pre-induction or prolonged salbutamol treatment was employed, most patients (8 of 10 and 7 of 9) experienced wheezing after intubation. In contrast, only one patient of those who received both salbutamol and methylprednisolone experienced wheezing (P=0.0058).Conclusions: Pretreatment with either salbutamol or combined inhaled salbutamol and oral methylprednisolone significantly improves lung function and decreases the incidence of wheezing after tracheal intubation. Methylprednisolone decreases incidence of wheezing more than salbutamol. Therefore, in patients with bronchial hyper reactivity, preoperative treatment with both methylprednisolone and salbutamol minimizes intubation-evoked broncho-constriction.

Background and the purpose of the study: The occurrence of Extended Spectrum b- Lactamase (ESBL)-producing Entrobacteriaceae has been steadily increased in recent years, resulting in limitation of therapeutic options. The purpose of this study was to determine prevalence of ESBL-producing Entrobacteriaceae isolated from Intensive Care Units (ICUs) and to investigate their phenotypic and genotypic characteristics. Methods: A total of one hundred fifty isolates were collected from urine and urinary catheter, sputum, blood, wound and other clinical samples from patient admitted in ICUs. All isolates were identified by biochemical tests and then were screened for ESBL production by Disk Agar Diffusion (DAD) according to the Clinical and Laboratory Standards Institute (CLSI) guideline. The species that met screening criteria were further tested for the effects of clavulanic acid by confirmatory method. ESBL-positive species were tested for blaTEM and blaSHV genes by PCR assay. Results: Of total of 150 bacterial isolates, 133(89.3%) isolates were positive in the resistance to all tested cephalosporin indicators; and 89(59.3%) isolates were confirmed as ESBL producer. Klebsiella pneumoniae, Escherichia coli and Entrobacter spp. were the most ESBL-producing species. All isolates were sensitive to imipenem. The blaTEM (55.5%) was the most common gene detected in ESBL phenotypic-positive isolates using PCR method.Conclusion: The present study shows high prevalence of ESBL-producing Entrobacteriaceae from ICU patients. The increased rate of these species is mainly due to the inadequate and unnecessary antimicrobial therapy. Rational administration of b-lactams and appropriate infection control policies may reduce prevalence of ESBL-producing bacteria in ICUs.

Background and the purpose of the study: Helicobacter pylori express abundant amounts of AhpC enzyme that functions to reduce organic hydroperoxides (ROOH) into the corresponding non-toxic alcohols (ROH). This conserved antigen has been earlier described as specific and unique for H. pylori and therefore, both H. pylori AhpC and Anti-AhpC could be useful in the development of serologic and stool antigen tests, to detecting and monitoring H. pylori infection. AhpC may also serves as a potential target for an antimicrobial agent or for vaccine development. The aim of this study was to simplify isolation and purification of the AhpC and production of a highly specific polyclonal antibody against it. Methods and Results: In this paper a simple method was used for protein purification and antibody production which avoids both the long term AhpC protein purification procedure and the addition of Freund’s adjuvant. One-dimensional preparative gel electrophoresis allows a single and short purification step and the high resolution capacity of this technique leads to a high level of purity of the protein and consequently to a very high specificity of the antibody. Moreover, it avoids contamination by other non-specific proteins which often appear during protein purification by column chromatographic techniques. Major Conclusion: The present method is simple, rapid and cost-effective and makes it possible to produce antibody for stool antigen enzyme immunoassay in short time and at low cost.

Background and purpose of the study: Bcl-2 and Cyclin D1 (CCND1) are key elements in cancer development and progression. Bcl-2 acts as a cell death suppressor and is involved in apoptosis regulation. Cyclin D1 is an important regulator of G1/S phase of the cell cycle progression. In addition, estrogen receptor (ER) is an important prognostic factor in breast cancer cells. Therefore it is important to determine the Bcl-2 and CCND1 expression in MCF7, T47D and MDA-MB-468 breast cancer cell lines with different ER status following Adriamycin (ADR) treatment. Methods: Cytotoxicity of ADR (250 and 500nM) after 1-5 days exposure of the cell lines was evaluated by MTT assay. The mRNA and protein levels of Bcl-2 and cyclin D1 in tested cell lines were also analyzed by RT-PCR and immunocytochemistry (ICC) methods. Results: ADR cytotoxicity was highest in MDA-MB-468 and lowest in MCF7 cells in a time-dependent manner. Bcl-2 mRNA increased in MCF7 and decreased in MDA-MB-468 after exposure to ADR but it was less detectable in T47D cells. The expression of CCND1 in MCF7 with high level of ER expression was higher than the other two cell lines in untreated conditions. However, CCND1 mRNA did not show significant changes after ADR treatment. Immunocytochemical analysis did not show significant differences between Bcl-2 protein expression in the presence or absence of ADR in MDA-MB-468 cell line while in T47D and MCF7 cells its expression decreased after exposure to ADR. In addition to nuclear expression of cyclin D1 in all cell lines, strong cytoplasmic expression of cyclin D1 protein was observed only in MCF7 and T47D cells. Conclusion: The tested cell lines with different levels of ER expression showed differential molecular responses to ADR that is important in tumor-targeted cancer therapy.

Background and the purpose of the study: Fluoroquinolones are an important group of antimicrobial agents that are used widely in the treatment of various infectious diseases.The purpose of the present study was to synthesize new N-piperazinyl quinolone derivatives with 5-chloro-2-theinyl group having possible antimicrobial activity.Methods: Reaction of ciprofloxacin (1), norfloxacin (2) and enoxacin (3) with a-bromoketone 10 or a-bromooxime derivatives 11a-c in DMF, in the presence of NaHCO3 at room temperature, afforded corresponding ketones 4a-c or oxime derivatives 5-7(a-c), respectively.Results and major conclusion: The synthesized compounds were tested against a series of Grampositive and Gram-negative bacteria. The results of MIC tests against both Gram-positive and Gram-negative bacteria revealed that ciprofloxacin derivatives (compounds 4a, 5a, 6a and 7a) were more active than norfloxacin and enoxacin analogues. Compound 5a, containing N-[2-(5-chlorothiophen-2-yl)-2-hydroxyiminoethyl] residue provided a high in vitro antibacterial activity against Gram-positive bacteria, with MIC of 0.06, 0.125, 0.5 and 0.125 mg/mL against S. aureus, S. epidermidis, E. feacalis and B. subtilis, respectively. Its activity was found to be 4 to 8 times better than reference drug (ciprofloxacin) against all Gram-positive bacteria with the exception of E. feacalis.