Both ACE inhibitors and non steroidal anti-inflammatory drugs (NSAIDs) are prescribed together in the elderly as different diseases may occur together. In vivo and in vitro interaction studies of ACE inhibitor (enalapril) was carried out with commonly used NSAID, flurbiprofen in carrageenan induced inflammation (CIIR) rats to check the anti-inflammatory response of NSAIDs in presence of enalapril and alone. In present study, altered anti-inflammatory response was observed for flurbiprofen when given simultaneously with enalapril by comparing decrease in paw size. Results were expressed in % reduction in paw size for every hour and were calculated for edema rate and percentage reduction. In vitro interaction studies carried out using HPLC and both the drugs were analyzed by assaying both drugs alone and in combination.The combination of enalapril and flurbiprofen showed increased activity of flurbiprofen as depicted by increase of % reduction and decrease in edema rate. It was also proved from AUC of the chromatogram of combine drugs. Since this study has certain limitation as a number of tested animals were small and the duration of anti-inflammatory response was checked for flurbiprofen alone and in combination with enalapril for few hours, further studies may be required to establish the strong relationship.

In this work, two methods are described for the simultaneous determination of clopidogrel bisulfate with HMG Co-A reductase inhibitors/statins. The first method comprised of quantitative determinations of clopidogrel bisulfate in presence of HMG Co-A reductase inhibitors (atorvastatin, pravastatin simvastatin and rosuvastatin) in buffers of pH 1, 4 (simulating gastric environments), pH 7.4 (simulating blood pH) and pH 9 (simulating intestinal pH) at body temperature (37ºC) using UV/VIS spectrophotometer. Derivative spectroscopy coupled with zero-crossing measurements was used for separating the interfering wavelengths of clopidogrel and statins. Least square regression analysis was performed to measure the concentrations of these drugs. It was observed that clopidogrel interacted with statins at all four pH, especially in simulated gastric environments. In the second case, reversed phase liquid chromatographic (RP-LC) method was developed for simultaneous determination and to investigate the interactions between clopidogrel and HMG Co-A reductase inhibitors. These interactions were evaluated by RP-LC in buffers of pH 1, 4, 7.4 and 9. These studies further supported the evidence of complexation between clopidogrel and statins as the area under the curve (AUC) was found increased in almost all four pH solutions.

Verapamil, a calcium channel blocker, is classified as a class IV anti-arrhythmic agent. It is used in the treatment of hypertension, as an important therapeutic agent for angina pectoris, ischemic heart disease, hypertension and hypertrophic cardiomyopathy. Many in-vivo studies have been carried out to find out the effects on concurrent use of calcium channel blocker with various groups of drugs. In the present paper an in-vitro approach was adapted to study the interaction of verapamil with commonly administered fluoroquinolones i.e. ciprofloxacin, levofloxacin, norfloxacin and sparfloxacin. The interaction studies were carried out in different simulated body fluids pH ranges from 1-9 at 37 ºC. To perform these studies first-derivative UV spectrophotometric (using zero-crossing technique) and simultaneous RP-HPLC methods were developed and validated. HPLC analysis was conducted on Shim-pack CLC-ODS (6.0 X 150 mm) column. The mobile phase constituted of acetonitrile: water (45:55), whose pH was adjusted to 2.8 and pumped at a flow rate of 1.2 mL min-1 at 230 nm. The results obtained from both methodologies indicated that the availability of verapamil was not affected by simultaneous administration of fluoroquinolones. Hence the two drugs could be safely administered concomitantly.

Um método isocrático de cromatografia líquida de alta resolução de fase reversa (RP-HPLC) foi desenvolvido para determinação de gemifloxacin a granel, em formulações e soro humano a 270 nm. A separação cromatográfica foi adquirida em uma coluna Purospher STAR C18 (250 × 4,6 mm, 5 µm) usando a fase móvel metanol:água (90:10, v/v) ajustada para pH 2,8 com ácido fosfórico 85% em fluxo de 1,5 mL min-1 a temperatura ambiente. As curvas de calibração mostraram-se lineares dentro do intervalo de 5-100 µg mL-1 com um coeficiente de correlação de 0,9998. Os limites de detecção (LOD) e de quantificação (LOQ) foram 0,015 and 0,045 µg mL-1, respectivamente. Os resultados de precisão intra- e inter-corridas e de exatidão foram 98,73-100,12%, que foram correlacionados através do teste t student. Este método foi aplicado para interações in vitro do gemifloxacino com elementos essencial e traço.

An isocratic reversed phase high-performance liquid chromatographic (RP-HPLC) method has been developed for the determination of gemifloxacin in bulk, dosage formulations and human serum at 270 nm. Chromatographic separation was achieved on Purospher STAR C18 (250 × 4.6 mm, 5 µm) column using mobile phase methanol:water (90:10, v/v) adjusted pH 2.8 via phosphoric acid 85% having flow rate of 1.5 mL min-1 at ambient temperature. Calibration curves were linear over range of 5-100 µg mL-1 with a correlation coefficient 0.9998. The limit of detection (LOD) and limit of quantitation (LOQ) were 0.015 and 0.045 µg mL-1, respectively. Intra and inter-run precision and accuracy results were 98.73-100.12% and then correlated through student'st-test. This method was further applied for in vitro interactions of gemifloxacin with essential and trace elements.

Simultaneous determination of moxifloxacin (MOX) and H2-antagonists was first time developed in bulk and formulations. Purospher STAR C18 (250 x 4.6 mm, 5 μm) column was used. The mobile phase (methanol: water: ACN, 60:45:5 v/v/v, pH 2.7) was delivered at a flow rate of 1.0 mL min-1, eluent was monitored at 236, 270 and 310 nm for cimetidine, famotidine and ranitidine, respectively. The proposed method is specific, accurate (98-103%), precise (intra-day and inter-day variation 0.098-1.970%) and linear (r>0.998). The LOD and LOQ were 0.006-0.018 and 0.019-0.005 μg mL-1, respectively. The statistical parameters were applied to verify the results. The method is applicable to routine analysis of formulations and interaction of MOX with H2-antagonist.

The present paper describes the effect of metals ions on the in vitro availability of enoxacin (a second generation quinolone antibiotic) owing to drug-metal interaction. These interaction studies were performed at 37 °C in different pH environments simulating human body compartments and were studied by UV spectroscopic technique. In order to determine the probability of these reactions different kinetic parameters (dissolution constants (K) and free energy change (ΔG)) for these reactions were also calculated. It is proposed that the structure of enoxacin contains various electron donating sites which facilitate its binding with metallic cations forming chelates. Hence taking food products, nutritional supplements or multivitamins containing multivalent cations at the same time as enoxacin, could reduce the absorption of the drug into the circulation and thus would decrease the effectiveness of the drug. In addition, the MIC of enoxacin for various microorganisms before and after interaction with metal ions was calculated which in most cases was increased which possibly could impair the clinical efficacy of the drug.

Simple, specific, economical and precise high performance liquid chromatographic method for the simultaneous determination of enalapril in presence of statins (rosuvastatin, atorvastatin and simvastatin) in API (active pharmaceutical ingredient) and formulation has been developed and validated. Chromatography was carried out at 25"C on a prepacked Purospher Star, C18 (5 mm, 250 x 4.6 mm) column with the isocratic mobile phase of acetonitrile: water (60:40 v/v) adjusting pH to 2.8. The UV detection was carried at 230 nm. The results obtained showed good agreement with the declared contents. Enalapril and statins separated in less than 10 mins with good resolution and minimal tailing and without interference of excepients. The method was linear in the range of 2.5-100 μgmL-1 for enalapril concentration with a correlation co-efficient 0.9995 and in the range 0.625-25 μgmL-1 for statins concentrations having correlation coefficient 0.9990 (inter and intraday CV<2 .0%). The recovery was 99-102%. The method was validated according to ICH guidelines and the acceptance criteria for accuracy, precision, linearity, specificity and system suitability were met in all cases. The proposed method can be used for quantitative determination of enalapril and statins alone or in combination from API and formulations.

1. A simple isocratic reversed phase high performance liquid chromatographic (HPLC) method using C18 column with ultraviolet detection at 225 nm has been described for quantitative determination of gliquidone in formulation and human serum. The system is operated at room temperature using a mobile phase consisting of methanol: water (90:10) adjusted to pH 3.50 with phosphoric acid with a flow rate of 1 in Lmin-1. Methylparaben is successfully used as an internal standard. The assay is reproducible, linear (concentration range of 0.60-25 µmL-1) with correlation coefficient of 0.9999 and accurate (99.23 to 102.78%). The intra and inter run precision results are 1.14 and 1.32%. The LOD and LOQ values are 0.03 and 0.6 µmL-1, respectively There are no interfering peaks duetothe excipients present in the pharmaceutical tablet. Thus, the proposed method is simple and suitable for the analysis of active ingredient in tablet dosage form and human serum.

Patients diagnosed with diabetes are prescribed a large number of medications for appropriate therapy, increasing risk of side effects or drug interactions. Metformin, a guanidine derivative is commonly used as a drug of choice for the treatment of non insulin dependent diabetes mellitus. There are a number of interactions reported for metformin. On the other hand, NSAIDs are generally used for the treatment of pain, fever and inflammation, particularly arthritis. Since the former drug is used in long term therapy, it may be co-administered with other drugs. In the present paper, we investigated the in-vitro availability of metformin in presence of commonly used NSAIDs, like diclofenic sodium, flurbiprofen, ibuprofen, mefenamic acid, meloxicam and tiaprofenic acid. These studies were carried out using modified BP 2007 dissolution test apparatus in simulated body environments at 37°C. These drug interactions were analyzed by UV/ VIS spectroscopy and the effect on the availability of both metformin and NSAIDs in presence of each other was calculated by applying simultaneous equation which was derived by modifying Beers law. The interactions were further studied by RP-HPLC with mobile phase consisting of methanol and water (80:20 v/v) maintained at a flow rate of 1 mLmin-1 at isobestic point 241 nm (metformin, diclofenac sodium, flurbiprofen, tiaprofenic acid, ibuprofen, meloxicam and mefenamic acid) respectively The results showed that the in vitro availability of NSAIDs and metformin owing to interaction was depressed through the formation of charge transfer complexes which was found to be associated with inter- and intra-molecular rearrangement of the electronic cloud of the interacting drugs. Henee it is envisaged that concurrent administration of metformin and NSAIDs could alter the bio-availability and impair the clinical efficacy of both drugs. Effect of pH is also studied on these drug-drug interactions.

An accurate, sensitive and least time consuming reverse phase high performance liquid chromatographic (RP-HPLC) method for the estimation of ceftriaxone in the presence of statin drugs in formulation and human serum has been developed and validated. Chromatographic separation was conducted on prepacked Purospher Star, C18 (5 mm, 250 x 4.6 mm) column at room temperature usingmethanol:water:acetonitrile (70:15:20 v/v/v) as amobile phase, pH adjusted at 2.8 with ortho-phosphoric acid and at a flow rate of 1.0 mL/minute, while UV detection was performed at 240 nm. The results obtained showed a good agreement with the declared content. The method shows good linearity in the range of 2.5-25 µg/mL with a correlation coefficient 0.9966 - 0.9998 (inter-and intra-day RSD < 2 %).The limit of detection and quantification for ceftriaxone and statins in pharmaceutical formulation and serum were inthe range 0.124 -1.006 µg/mL. Analytical recovery was >98.72 %. The proposed methodmay be used forthe quantitative analysis of commonly administered statin's i.e. simvastatin, rosuvastatin atorvastatin and pravastatin alone or in combination with ceftriaxone from raw materials, dosage formulations and in serum. The established HPLC method is rapid, accurate and selective, because of its sensitivity and reproducibility.

An isocratic reversed phase high-performance liquid chromatographic (RP-HPLC) method has been developed for the simultaneous determination of gemifloxacin and diuretics (hydrochlorothiazide and furosemide) in bulk, dosage formulations and human serum at 232 nm. Chromatographic separation was achieved on Purospher Start C18 (250 mm x 4.6 mm, 5 µm) column using mobile phase, methanol: water: acetonitrile (70:25:5 v/v/v) adjusted to pH 3.0 via phosphoric acid 85% having flow rate of 0.8 mL min -1 at room temperature. Calibration curves were linear over range of 0.5-10 µg mL -1 with a correlation coefficient ± 0.999. LOD and LOQ were in the ranges of 0.75-2.56 µg mL -1. Intra and inter-run precision and accuracy results were 98.26 to 100.9.

In the present paper, we describe the in vitro availability of simvastatin, a potent HMG-CoA reductase inhibitor, in presence of losartan potassium, which is a non-peptide angiotensin II receptor antagonist. These studies were carried out at 37, 48 and 60°C in different pH environments simulating human body compartments. The reactions were studied by UV spectroscopy and the availability of both drugs in presence of each other was determined by deriving a simultaneous equation for two component system through modifcation of Beer`s law. The interactions were further characterized by IR and H¹NMR spectroscopic techniques. It was observed that availability of simvastatin in presence of losartan at 37 ºC in simulated gastric juice, at pH 7.4 and pH 9.0 was blocked by losartan through the formation of a charge-transfer complex while the availability of losartan in turn was immensely increased. In pH 4.0 these effects were reversed, availability of simvastatin increased and the availability of losartan was depressed. Similar results were observed at higher temperatures.

High Performance Liquid Chromatographic method was developed and applied for the simultaneous determination of diltiazem and fluoroquinolones in bulk, pharmaceutical formulations and human serum in presence of caffeine as internal standard. A Hiber®, RP-18 column was used with mobile phase consisting of acetonitrile:methanol:water (30:20:50 v/v, pH 3.6) and quantitative evaluation was performed at 230 run. Suitability of this method for the quantitative determination of the drugs was proved by validation in accordance with the requirements laid down by International Conference on Harmonization (ICH) guidelines.The method was selective, precise, accurate and can be used for routine analysis of pharmaceutical preparations, quality control and clinical laboratories.