Journal of Young Pharmacists : 2011 - 3(4)

Formulation and evaluation of cephalexin extended release matrix tablets using 3 2 factorial design

V Jishnu — Fri,25 Nov 2011

V Jishnu, R Prabhakaran, RM Gilhotra

Journal of Young Pharmacists 2011 3(4):259-266

The aim of the present investigation was to prepare extended release film coated matrix tablets of cephalexin using binary mixture of two grades of hydrophilic polymer, hydroxypropyl methyl cellulose (HPMC), by direct compression method. Results of the preliminary trials indicated that the polymers used have significant release retarding effect on the formulation. To study the effect of concentration of polymers on drug release from matrix tablets, 3 2 full factorial design was applied. The concentration of HPMC K15M and HPMC 15cps were used as independent variables, while percentage drug release was selected as dependent variable. The dissolution data were fitted into zero-order, first-order, Higuchi and Korsemeyer-Peppas models to identify the pharmacokinetics and mechanism of drug release. Comparative study of dissolution profile of final batch F3 with market preparation (Sporidex AF 375) was done by similarity factor (f 2 ) determination and it was concluded that final formulation F3 (10% HPMC K15M, 17.5% HPMC 15cps) shows good similarity with the market product. The results of the accelerated stability study of final formulation F3 for 1 month revealed that storage conditions were not found to have made any significant changes in final formulation F3. The release of cephalexin was prolonged for 6 h by using polymer combinations of HPMC and a twice daily matrix tablet was formulated.

Preparation and characterization of pioglitazone cyclodextrin inclusion complexes

V Pandit — Fri,25 Nov 2011

V Pandit, R Gorantla, K Devi, RS Pai, S Sarasija

Journal of Young Pharmacists 2011 3(4):267-274

Pioglitazone, a class II Biopharmaceutical Classification System drug having poor water solubility and slow dissolution rate may have a negative impact on its subtherapeutic plasma drug levels leading to therapeutic failure. In order to improve its water solubility and thus dissolution, cyclodextrin complexation technique was followed. The phase solubility studies were carried using three different types of cyclodextrins viz., β, methyl-β and γ-cyclodextrins. The Gibbs free energy was calculated in order to determine ease of the complexation. Binary systems of pioglitazone with cyclodextrins were prepared by kneading method and spray drying method. The phase solubility profiles with all the three cyclodextrins were classified as A L -type, indicating the formation of 1:1 stoichiometric inclusion complexes. The complexation capability of cyclodextrins with pioglitazone increased in the order of methyl-β > β > γ-cyclodextrin. The Gibbs free energy was found to be in the order γ > methyl-β > β cyclodextrin. Characterization of inclusion complexes was done by solubility studies, in vitro dissolution studies, Fourier transformation-infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry and X-ray powder diffractometry studies. Inclusion complexes exhibited higher rates of dissolution than the corresponding physical mixtures and pure drug. Greater solubility was observed with spray-dried methyl-β cyclodextrin complexes (2.29 ± 0.001 mg/ml) in comparison to the kneaded methyl-β cyclodextrin complexes (1.584 ± 0.053 mg/ml) and pure drug (0.0714 ± 0.0018 mg/ml).

Formulation and optimization of mucoadhesive nanodrug delivery system of acyclovir

UV Bhosale — Fri,25 Nov 2011

UV Bhosale, V Kusum Devi, N Jain

Journal of Young Pharmacists 2011 3(4):275-283

Acyclovir is an antiviral drug used for the treatment of herpes simplex virus infections, with an oral bioavailability of only 10-20% [limiting absorption in gastrointestinal tract to duodenum and jejunum] and half-life of about 3 h, and is soluble only at acidic pH (pKa 2.27). Mucoadhesive polymeric nanodrug delivery systems of acyclovir have been designed and optimized using 2 3 full factorial design. Poly (lactic-co-glycolic acid) (PLGA) (50:50) was used as the polymer along with polycarbophil (Noveon AA-1) as the mucoadhesive polymer and pluronic F68 as the stabilizer. From the preliminary trials, the constraints for independent variables X 1 (amount of PLGA), X 2 (amount of pluronic F68) and X 3 (amount of polycarbophil) have been fixed. The dependent variables that were selected for study were particle size (Y 1 ), % drug entrapment (Y 2 ) and % drug release in 12 h (Y 3 ). The derived polynomial equations were verified by check point formulation. The application of factorial design gave a statistically systematic approach for the formulation and optimization of nanoparticles with the desired particle size, % drug release and high entrapment efficiency. Drug: Polymer ratio and concentration of stabilizer were found to influence the particle size and entrapment efficiency of acyclovir-loaded PLGA nanoparticles. The release was found to follow Fickian as well as non-Fickian diffusion mechanism with zero-order drug release for all batches. In vitro intestinal mucoadhesion of nanoparticles increased with increasing concentration of polycarbophil. These preliminary results indicate that acyclovir-loaded mucoadhesive PLGA nanoparticles could be effective in sustaining drug release for a prolonged period.

Antimicrobial activity of the extract of stem bark of Diplotropis ferruginea benth

GS Cerqueira — Fri,25 Nov 2011

GS Cerqueira, NFM Rocha, JRGS Almeida, APF de Freitas, EO Lima, JMB Filho, RM de Freitas, MFF Melo Diniz

Journal of Young Pharmacists 2011 3(4):284-286

This is the first report about the antibacterial activity of Diplotropis ferruginea Benth. In this study, the ethanol extract of D. ferruginea was tested for its antimicrobial activity against strains gram-positive and gram-negative. In order to determine the minimal inhibitory concentration, assays were carried out by micro dilution method. The extract was screened for antimicrobial activity, and it showed antibacterial activity against Escherichia coli and Pseudomonas aeruginosa.

Litsea deccanensis ameliorates myocardial infarction in wistar rats: Evidence from biochemical and histological studies

P Bharath Kumar — Fri,25 Nov 2011

P Bharath Kumar, M Mari Kannan, S Darlin Quine

Journal of Young Pharmacists 2011 3(4):287-296

The present study was designed to evaluate the cardioprotective effects of methanolic extract of Litsea deccanensis (MELD) against isoproterenol-induced myocardial infarction in rats by studying cardiac markers, lipid peroxidation, lipid profile, and histological changes. Male Wistar rats were treated orally with MELD (100 and 200 mg/kg) daily for a period of 21 days. After 21 days of pretreatment, isoproterenol (100 mg/kg) was injected subcutaneously to rats at an interval of 24 h for 2 days to induce myocardial infarction. Isoproterenol-induced rats showed significant (P < 0.05) increase in the levels of serum creatine kinase, lactate dehydrogenase, thiobarbituric acid reactive substances, and lipid hydro peroxides. The serum lipid levels were altered in the isoproterenol-induced myocardial infarcted rats. The histopathological findings of the myocardial tissue evidenced myocardial damage in isoproterenol-induced rats. The oral pretreatment with MELD restored the pathological alterations in the isoproterenol-induced myocardial infarcted rats. The MELD pretreatment significantly reduced the levels of biochemical markers, lipid peroxidation and regulated the lipid profile of the antioxidant system in the isoproterenol-induced rats. An inhibited myocardial necrosis was evidenced by the histopathological findings in MELD pretreated isoproterenol-induced rats. Our study shows that oral pretreatment with MELD prevents isoproterenol-induced oxidative stress in myocardial infarction. The presence of phenolic acid and flavonoid contents were confirmed by preliminary phytochemical tests. The reducing power and free radical scavenging activities of the MELD may be the possible reason for it pharmacological actions.

Cardioprotective effects of Lagenaria siceraria fruit juice on isoproterenol-induced myocardial infarction in wistar rats: A biochemical and histoarchitecture study

A Upaganlawar — Fri,25 Nov 2011

A Upaganlawar, R Balaraman

Journal of Young Pharmacists 2011 3(4):297-303

The present study was designed to evaluate the cardioprotective effects of Lagenaria siceraria fruit juice in isoproterenol-induced myocardial infarction. Rats injected with isoproterenol (200 mg/kg, s.c.) showed a significant increase in the levels of serum uric acid, tissue Na ++ and Ca ++ ions and membrane-bound Ca +2 -ATPase activity. A significant decrease in the levels of serum protein, tissue K + ion, vitamin E level, and the activities of Na + /K + -ATPase and mg +2 -ATPase was observed. Isoproterenol injected rats also showed a significant increase in the intensity of lactate dehydrogenase isoenzyme and histopathologic alterations in the heart. Treatment with L. siceraria fruit juice (400 mg/kg/day, p.o.) for 30 days and administration of isoproterenol on 29 th and 30 th days showed a protective effect on altered biochemical and histopathologic changes. These findings indicate the cardioprotective effect of L. siceraria fruit juice in isoproterenol-induced myocardial infarction in rats.

Oxidative stress induced by fluoroquinolones on treatment for complicated urinary tract infections in Indian patients

V Talla — Fri,25 Nov 2011

V Talla, PR Veerareddy

Journal of Young Pharmacists 2011 3(4):304-309

The aim of the study is to examine the oxidative stress in patients on fluoroquinolones (ciprofloxacin, levofloxacin, gatifloxacin) therapy for complicated urinary tract infections and to correlate with plasma concentrations at different time intervals. Superoxide dismutase (SOD), glutathione, plasma antioxidant status and lipid peroxides were evaluated in 52 patients on different dosage regimens up to 5 days. There is significant and gradual elevation of lipid peroxide levels in patients on ciprofloxacin (3.6 ± 0.34 nmol/ml to 6.2 ± 0.94 nmol/ml) and levofloxacin (3.5 ± 0.84 nmol/ml to 5.1 ± 0.28 nmol/ml) dosage regimen but not with gatifloxacin (3.5 ± 0.84 nmol/ml to 3.74 ± 0.17 nmol.ml). There was substantial depletion in both SOD and glutathione levels particularly with ciprofloxacin. On the 5 th day of treatment, plasma antioxidant status decreased by 77.6% %, 50.5%, 7.56% for ciprofloxacin, levofloxacin and gatifloxacin respectively. In conclusion ciprofloxacin and levofloxacin induce more reactive oxygen species that lead to cell damage than gatifloxacin irrespective of their concentrations in patient population.

Synthesis, characterization and biological activity studies of 1,3,4-oxadiazole analogs

KI Bhat — Fri,25 Nov 2011

KI Bhat, K Sufeera, P Chaitanya Sunil Kumar

Journal of Young Pharmacists 2011 3(4):310-314

The reaction of p-bromoanilino acetohydrazide(II) with aromatic aldehydes in alcohol yielded 2-[4-bromo aniline] N-substituted benzylidine hydrazides (IIIa-IIIj), which in presence of yellow mercuric oxide and iodine in DMF, yielded corresponding 4-bromo[(N-5-substituted 1,3,4 oxadiazole-2 -yl)methyl]aniline (IVa-IVj). Structures of the compounds synthesized were confirmed by IR, 1 HNMR and MASS spectroscopic analysis. The newly synthesized compounds were screened for antibacterial, antifungal and anti-inflammatory activities. Some of the compounds showed remarkable antibacterial, antifungal and anti-inflammatory activities.

High performance liquid chromatographic fluorescence detection method for the quantification of rivastigmine in rat plasma and brain: Application to preclinical pharmacokinetic studies in rats

K Arumugam — Fri,25 Nov 2011

K Arumugam, MR Chamallamudi, SR Mallayasamy, R Mullangi, S Ganesan, L Jamadar, A Ranjithkumar, N Udupa

Journal of Young Pharmacists 2011 3(4):315-321

A highly sensitive and selective high performance liquid chromatographic fluorescence detection method has been developed and validated for the quantification of rivastigmine in rat plasma and brain. Protein precipitation and one-step liquid-liquid extraction techniques were utilized for the extraction of RSM from brain and plasma, respectively, along with an internal standard. The chromatographic separation was achieved with a column inertsil ODS-3V and a mobile phase consisting of ammonium acetate buffer (20 mM, pH 4.5) and acetonitrile (76:24, v/v) delivered at a flow rate of 1 ml/min. The lower limit of quantitation for the developed method was 10 ng/mL for both matrices. The method was found to be accurate and reproducible and was successfully used to quantify levels of RSM in plasma and brain following intravenous administration of RSM in rats.

Pharmacokinetic evaluation of paclitaxel in South Indian cancer patients: A prospective study

J Vasantha — Fri,25 Nov 2011

J Vasantha, G Kannan, T Goud, T Palani, R Vanitha, R Anitha, JMM Priya

Journal of Young Pharmacists 2011 3(4):322-328

Paclitaxel is a promising drug in the treatment of different solid tumors. It exhibits nonlinear pharmacokinetics, particularly when administered as a constant rate infusion for shorter duration (e.g., 3 h). Because of the nonlinearity, relatively small changes in dose may lead to large changes in peak plasma concentration and total drug exposure. The study was conducted to evaluate the pharmacokinetics of different doses of paclitaxel administered intravenously as an infusion. A prospective study was conducted in 23 cancer patients aged between 28 and 74 years, treated with paclitaxel (130, 200, 230, and 260 mg/m 2 ) over 3 h as constant rate infusion. Plasma samples were collected from all patients at 0, 1, and 3 h and for five patients at 5 and 13 h and paclitaxel concentrations were determined using high-performance liquid chromatography method. The overall mean clearance was found to be 47.5847 ± 142.028 l/h; the mean volume of distribution was 142.028 ± 73.438 l; mean elimination rate constant was 0.336 ± 0.002/h; mean half-life was 2.086 ± 0.009 h; mean area under the curve (AUC) was 5.5917 ± 2.707 mg/ml*h; and the mean of mean residence time was 2.980 ± 0.0131 h. Paclitaxel showed nonlinear kinetics and the pharmacokinetic parameters calculated were similar to those quoted in the literature. The peak plasma concentration at 130 mg dose level was 2 m/ml, but an increase in dose was not associated with proportional increase in plasma concentration. No significant difference was found between pharmacokinetic parameters such as clearance, volume of distribution, and AUC at different dose levels.

Drug-drug interactions in hospitalized cardiac patients

UV Mateti — Fri,25 Nov 2011

UV Mateti, T Rajakannan, H Nekkanti, V Rajesh, SR Mallaysamy, P Ramachandran

Journal of Young Pharmacists 2011 3(4):329-333

Drug-drug interactions (DDIs) are defined as two or more drugs interacting in such a manner that the effectiveness or toxicity of one or more drugs is altered. DDI in patients receiving multidrug therapy is a major concern. The aim of the present study was to assess the incidence and risk factors of DDIs in patients admitted in cardiology unit of a teaching hospital. A prospective, observational study was carried out for a period of 3 months (April-July 2009). During the study period, a total of 600 prescriptions were analyzed and it was found that 88 patients had at least one DDI. The percentage of DDIs was higher in females compared to males (56.82% vs. 43.18%). DDIs were observed more in the age group of 60 years and above (57.96). Patients with more than 10 prescribed drugs developed DDIs more frequently [58 (65.91%)]. Heparin [55 (62.25%)] and aspirin [42 (47.72%)] were the most common drugs responsible for DDIs. Bleeding was the commonest clinical consequence [76 (86.63%)] found in this study population. On assessment of severity of DDIs, majority of the cases were classified as moderate in severity (61.36%). Aging, female gender and increase in concurrent medications were found to be associated with increased DDIs. Patients having these risk factors can be actively monitored during their stay in the cardiology department to identify DDIs.

Pharmacy education in India: Strategies for a better future

V Jishnu — Fri,25 Nov 2011

V Jishnu, RM Gilhotra, DN Mishra

Journal of Young Pharmacists 2011 3(4):334-342

In this world of specialization and globalization the pharmacy education in India is suffering from serious backdrops and flaws. There is an urgent need to initiate an academic exercise aimed at attaining revamping of curriculum, keeping in pace with current and emerging trends in the field of pharmacy. Unfortunately all these years, enough emphasis was not laid on strengthening the components of Community Pharmacy, Hospital and Clinical pharmacy, while designing curriculum at diploma and degree levels of teaching. The curriculum followed by almost all universities in India are no were up to the world standards and students are still getting the 20-30 yrs older compounding practical exposure in labs during the graduation level. The article emphasises the concept of innovation ecosystems and quality management. Application of TQM to the educational system improves the present situation. The counseling system which serves to be the gateway of the students for entry into the profession should be brought under the scanner. Introducing specializations at the graduation level will result in professional expertise and excellence. Education is a customer focused industry and every student should be capable of evaluating themselves for continuously improving their quality and professionalism. Teacher focused mastery learning should give away to student focused smart learning. An educational institution should provide the student with a stress-free atmosphere for learning and developing his intellectual capabilities. Every college should have a counseling centre to address the problems of students in their academic and personal life. An emphasis on the concept of quality teacher is included. Revival of the pharmacy education in India is the need of the hour which in turn will pave the way for the up gradation of the pharmacy profession in the country.

Buyouts of Indian pharmaceutical companies by multinational pharmaceutical companies: An issue of concern

D Sreedhar — Fri,25 Nov 2011

D Sreedhar, MD Janodia, VS Ligade

Journal of Young Pharmacists 2011 3(4):343-344