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In modern medication, drug-loaded novel polymeric nanoparticles have potential advantages over conventional dosage forms. The present study focused on the formulation development and evaluation of newly introduced angiotensin receptor blocker (ARB) eprosartan mesylate loaded biodegradable acid terminated poly(lactide-co-glycolide) (50:50) nanoparticle using double emulsion solvent evaporation technique. This methodology was found to improve the therapeutic efficacy as Eprosartan Mesylate belongs to BCS class-II and water-insoluble antihypertensive drug with 13% bioavailability. In the earlier stage, screening was performed to find out the suitable combination of excipients (Polyvinyl alcohol, Dichloromethane and Ethanol) to formulate the nanoparticles. In this present study, the physical and chemical properties of polymer and drug were determined before and after the formulation of nanoparticles using experimental techniques, such as Differential Light Scattering (DLS), zeta potential, X-ray Deffractometry (XRD), Fourier-Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Liquid Chromatography-Mass Spectrometry (LC-MS/MS) analysis. The eprosartan mesylate loaded PLGA nanoparticles showed fairly monodispersive, as determined from DLS (average particle diameter 136 nm, Poly Dispesity Index = 0.3). The zeta potential was found to be -10.8mV. This formulation showed a prolonged improved drug release (82.03%) for 360 hours in phosphate buffer (pH7.4) as compared to the conventional marketed dosage form. In-vitro release kinetics data of NPs (R2=0.8979) and diffusion exponent values (n=0.3328) suggested that optimized followed the Korsmeyer-Peppas model with Fickian mechanism.

Objective: Acotiamide, a prokinetic drug used to treat Functional Dyspepsia, which acts by modulating gastric motility. However, in this present study, a simple and accurate bioanalytical method was developed for the estimation of Acotiamide in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and validated according to US-FDA guideline. Methods: The method was developed in blank human blood plasma; propranolol was used as internal standard (IS). Protein Precipitation technique was followed for the extraction of the drug from the plasma sample. In liquid chromatography, the C18 analytical column (50 x 3 mm, particle size-5 μm) was used; as a mobile phase, 0.1% formic acid in Mili Q water, and ACN with methanol (1:1) used, at 0.50 ml/min flow rate. Detection was done by positive electrospray ionization (ESI) with a run time of 7 min in multiple reaction monitoring (MRM) mode. Eight calibration concentrations were taken, ranging from 1.5625-200 ng/ml for Acotiamide. Different stability studies were performed and obtained results found within the acceptable range. Moreover, a comparative pharmacokinetic analysis was done in 24 healthy human volunteers in a single dose, randomized, crossover study. Results: The precursor to production reaction was; m/z 451.200 → 271.200 for Acotiamide and m/z 260.300 → 116.100 m/z for IS. The obtained calibration curve was linear, with a mean r2value 0.9953. Among the pharmacokinetic parameters, Cmax and Tmax were 25.71±2.31,23.61±2.32 ng/ml; 2.54±0.12, 2.43±0.21 h for reference and test samples, respectively. Conclusion: No major adverse events were noted in the clinical phase, the developed method was accurate and linear; obtained pharmacokinetic parameters hence represented.

Paclitaxel, a potential anticancer agent against solid tumors has been restricted from its oral use due to poor water solubility as well as Pgp efflux property. The present study was aimed to improve the oral bioavailability of paclitaxel through development of (o/w) nanoemulsion consisting of Capryol 90 as internal phase with Tween 20 as emulsifier with water as an external phase. Formulations were selected from the nanoemulsion region of pseudo-ternary phase diagrams, formulated by aqueous titration method. The developed nanoemulsion has been characterized by its thermodynamic stability, morphology, droplet size, zeta potential, viscosity where in vitro release was evaluated through dialysis. Paclitaxel nanoemulsion exhibited thermodynamical stability with low viscosity, nano-sized oil droplets in water with low poly-dispersity index. The shelf life of the paclitaxel nanoemulsion was found to be approximately 2.38 years. Increased permeability through the Caco-2 cell monolayer and decreased efflux is great advantageous for nanoemulsion formulation. The effects of paclitaxel nanoemulsion on breast cancer cell proliferation, morphology and DNA fragmentation were analyzed in vitro which showed significant anti-proliferation and decreased IC50 values in nanoemulsion group which may be due to enhanced uptake of paclitaxel through the oil core. Moreover, the absolute oral bioavailability and sustained release profile of the paclitaxel nanoemulsion evaluated in mouse model was found to improve up to 55.9%. The concentration of paclitaxel in mice plasma was determined by our validated LC-MS/MS method. By reviewing the significant outcome of the present investigation based on stability study, Caco-2 permeability, cell proliferative assay and pharmacokinetic profile it may be concluded that the oral nanoemulsion has got encouraging advantages over the presently available formulations of this injectable chemotherapeutic drug.

Background This study was aimed to investigate the relative bioavailability of fixed-dose-combination (FDC) product of amlodipine, telmisartan and hydrochlorothiazide with individual marketed products in healthy male volunteers. Control of blood pressure with fixed dose combination of the above drugs acting through different mechanism have a benefit of convenient dosing in terms of compliance, lower the dose and subsequently reduce the side effects. Methods The authors investigated the relative bioavailability under a fasting state of the 3 drugs in a randomized, open-label, 2-treatment, 2-period, 2-sequence, crossover bioequivalence study with a washout period of 21 days. Plasma concentration of the analytes were assayed in timed samples with a simple, highly sensitive and rapid validated method using HPLC coupled to tandem mass spectrometry that had a lower limit of quantification of 1 ng/mL for all the 3 components. Results Test and reference formulations gave a mean Cmax of 5.234±0.914 ng/mL and 4.991±0.563 ng/mL, 108.839±13.601 ng/mL and 114.783±12.315 ng/mL and 97.814±10.779 ng/mL and 93.731±10.018 ng/mL for amlodipine, telmisartan and hydrochlorothiazide respectively. The AUC0-t of amlodipine, telmisartan and hydrochlorothiazide was 161.484 ng.h/mL, 1 917.644 ng.h/mL and 822.847 ng.h/mL for test formulation and 162.108 ng.h/mL, 2 014.764 ng.h/mL and 829.323 ng.h/mL for reference in the fasting state. Conclusion The 90% confidence intervals for the test/reference ratio of the pharmacokinetic parameters in fasting state (mean Cmax, AUC0-t, and AUC0-∞) were within the acceptable range of 80.00-125.00. Thus, these findings clearly indicate that the FDC product is bioequivalent with the individual marketed products in terms of rate and extent of drug absorption and is well tolerated with no significant adverse reactions.

Background: Enalapril (EPL) is an angiotensin-converting enzyme inhibitor for the treatment of hypertension and chronic heart failure. Enalaprilat (EPLT) is an active metabolite that contributes to the overall activity of EPL. Aim: To quantitate EPL along with its metabolite EPLT using LC–MS/MS, a bioanalytical method was developed and validated with tolbutamide in human plasma using a protein precipitation technique. Results: The sensitive and selective method has an LLOQ of 1 ng/ml with a linearity range of 1–500 ng/ml for both EPL and EPLT using 300 µl of plasma without any matrix effect. Conclusion: Linearity, specificity, accuracy, precision and stability, as well as its application to the analysis of plasma samples after oral administration of 20 mg of EPL maleate in healthy volunteers demonstrate applicability to bioavailability/bioequivalence studies., Lay abstract: The present study describes a sensitive, selective, simple, accurate and reproducible LC–MS/MS method for the simultaneous determination of both enalapril (EPL) and enalaprilat (EPLT) in human plasma. The results obtained indicate the high sensitivity of the described method for analysis of EPL and EPLT, which render this method particularly useful for pharmacokinetic or bioequivalence studies. The proposed method has been applied for the analysis of EPL and EPLT in the plasma of healthy volunteers in a single-dose pharmacokinetic study.

A novel sensitive, specific, reproducible and innovative reverse-phase high-performance liquid chromatographic method was developed for the detection of olmesartan medoxomil. A Hypersil BDS C18, 250 × 4.6 mm, 5 μm particle size column with a mobile phase composed of acetonitrile and 10 mM KH2PO4 buffer (pH 3.5) in a ratio of 55 : 45 v/v was used at a flow rate of 1.0 mL min−1 and the effluents were monitored at 250 nm. The calibration curve was linear in the range of 5.0 to 150.0 μg mL−1 with a determination coefficient (r2) of 0.998 that had been calculated by a least-squares regression method. The method is simple and rapid with a run time of 8.0 min. The method was fully validated according to ICH guidelines. This sensitive method with a LOD of 10.0 ng mL−1 and LOQ of 30.0 ng mL−1 showed precision in the range of 0.58–0.97% with an accuracy ranging between 98.84 and 101.53% and is selective for nanoemulsion assay and solubility determination in different matrices (oils, surfactants and mixtures of both). This method was successfully applied to quantitatively assess the solubility of olmesartan medoxomil in various oils, surfactants and mixtures of both. The innovative application of this method was the assay of olmesartan medoxomil, for the first time, in novel formulations such as in a nanoemulsion. Thus it acts as a guideline for preliminary screening studies for novel nanoemulsion formulations apart from just being a HPLC method.