Separation and Characterization of Novel Degradation and Process Related Impurities of Bedaquiline Bulk Drug.

Bedaquiline (BDQ) is a new drug approved by United States Food and Drug Administration (USFDA) in 2012 for the treatment of drug-resistant tuberculosis, which has become a major threat globally. The manuscript presents the development of three liquid chromatography (LC) based analytical methods. The first is a stability indicating RP-HPLC (reverse phase-high performance liquid chromatography) method to analyze the BDQ in presence of its degradation products.

Etoposide encased folic acid adorned mesoporous silica nanoparticles as potent nanovehicles for enhanced prostate cancer therapy: synthesis, characterization, cellular uptake and biodistribution.

The present research was motivated by the dire need to design a targeted and safe Nano-vehicle for delivery of Etoposide (ETE), which would be tolerant of normal cells and exclusively toxic to prostate cancer cells. The folic acid functionalized mesoporous silica nanoparticles (MSNs) constructed by using a facile method acting as a unique selective platform for ETE delivery for effective prostate cancer treatment. FA@MSNs possessed good payload and encouraging in vitro release was obtained for ETE caged inside FA-MSNs compared with ETE-MSNs alone.

Investigation of in vitro permeability and in vivo pharmacokinetic behavior of bare and functionalized MCM-41 and MCM-48 mesoporous silica nanoparticles: a burst and controlled drug release system for raloxifene.

In the present work, MCM-41 and MCM-48 type of nanoparticles were successfully engineered. Effect of nanosize and amine functionalization on drug release, in vitro intestinal absorption and in vivo pharmacokinetic behavior was investigated in a comprehensive manner. The tailor-made bare and surface decorated MCM-41 and MCM-48 were synthesized and evaluated for their mesoporous skeleton, pore size, particle size, surface area, zeta potential, etc.

Facile development, characterization, and evaluation of novel bicalutamide loaded pH-sensitive mesoporous silica nanoparticles for enhanced prostate cancer therapy.

It is a challenge to deliver therapeutics exclusively to cancer cells, while sparing the normal cells. However, pH-sensitive delivery systems have proved to be highly efficient in fulfilling this task due to their ability to provide on-demand and selective release of drug at acidic tumor sites. As a proof of concept, here pH responsive drug delivery system based on mesoporous core shell nanoparticles (NPs) surrounded with poly acrylic acid (PAA) layers were prepared employing a facile synthesis strategy.

Advances in the Development of Novel Factor Xa Inhibitors: A Patent Review.

Development of new anticoagulants has been in constant demand throughout the world due to increasing rate of morbidity and mortality caused by thrombotic diseases. Factor Xa (FXa), one of the enzymes and validated target for anticoagulation, regulates the production of thrombin in the coagulation cascade. The importance of oral FXa inhibitors like rivaroxaban, apixaban and edoxaban in thromboembolic conditions is well supported by increasing number of patents and research publications during the recent years.

Tailor-made pH-sensitive polyacrylic acid functionalized mesoporous silica nanoparticles for efficient and controlled delivery of anti-cancer drug Etoposide.

A multifaceted therapeutic platform has been proposed for controlled delivery of Etoposide (ETS) leading to a synergistic advantage of maximum therapeutic efficacy and diminished toxicity. A state of the art pH responsive nanoparticles (NPs) MSNs-PAA consisting of mesoporous silica nanoparticles core and polymeric shell layers, were developed for controlled release of model anti-cancer drug ETS. Graft onto strategy was employed and amination served as an interim step, laying a vital foundation for functionalization of the MSN core with hydrophilic and pH responsive polyacrylic acid (PAA).

Facile Synthesis of Chitosan Capped Mesoporous Silica Nanoparticles: A pH Responsive Smart Delivery Platform for Raloxifene Hydrochloride.

An encapsulation of model drug raloxifene hydrochloride (RAL) inside the chitosan decorated pH responsive mesoporous system has a greater potential for accumulating in the tumor cells. The present study involves synthesis of surface modified mesoporous silica nanoparticles (MSN) with the aim of achieving pH sensitive drug delivery system. A silanol skeleton of MSN has been productively modified to amine intermediate which served as a firm platform to adapt chitosan grafted assembly and systematically evaluated.

Stress degradation of edaravone: Separation, isolation and characterization of major degradation products.

In the present study the International Conference on Harmonization-prescribed stress degradation was carried out to study the degradation profile of edaravone. To establish a Quality by Design (QbD)-assisted stability-indicating assay, the reaction solutions in which different degradation products were formed were mixed. Plackett Burman and central composite design were used to screen and optimize experimental variables to resolve edaravone and its impurities with good peak symmetry using an RP C column.

Preparation and physicochemical characterization of ingredients of Indian traditional medicine, .

Background: is an ayurvedic formulation used in the treatment of cardiac disorders. It contains the purified roots of (), (), fruits of (), (), (Sulfur), (Cinnabar) and (Sodium metaborate) as per . The purification () process changes the physiochemical properties of the raw materials which need to be studied and understood.

Preparation and characterization of microemulsion of cilostazol for enhancement of oral bioavailability.

Cilostazol is a promising drug for antiplatelet combination therapy that is very important for treatment for various cardiovascular disorders. However, oral delivery of this drug is greatly impeded by the poor solubility in aqueous solutions. The aim of this study was to develop microemulsion (ME) delivery system capable of improving the drug bioavailability.

Optimization of the in vitro oxidative biotransformation of glimepiride as a model substrate for cytochrome p450 using factorial design.

Background And Purpose Of The Study: Glimepiride (GLM) was chosen as a model substrate in order to determine the kinetic parameters for in vitro metabolism via human liver micrososmes (HLM). We aimed to optimize the turnover of the substrate by the test system in relation to incubation time and HLM concentration in such a way that it was linearly dependent on time and less than 20% of the substrate was consumed which utilized the lowest amount of the HLM. Further we aimed to report Km and Vmax values for GLM.

Nanosuspension of efavirenz for improved oral bioavailability: formulation optimization, in vitro, in situ and in vivo evaluation.

Context: Nanosuspensions (NSs) of poorly water-soluble drugs are known to increase the oral bioavailability.

Objectives: The purpose of this study was to develop NS of efavirenz (EFV) and to investigate its potential in enhancing the oral bioavailability of EFV.

Materials And Methods: EFV NS was prepared using the media milling technique.

RP-HPLC method for simultaneous determination of butenafine hydrochloride and betamethasone dipropionate in a cream formulation.

An RP-HPLC method has been developed for the simultaneous determination of butenafine hydrochloride and betamethasone dipropionate on an Inertsil C18 column (250 x 4.6 mm id) using a mobile phase gradient consisting of methanol and water at a flow rate of 1 mL/min. Detection was carried out at 254 nm.

Biological Evaluation of Polyherbal Ayurvedic Cardiotonic Preparation "Mahamrutyunjaya rasa".

Mahamrutyunjaya rasa (MHR), an Ayurvedic formulation, used as cardiotonic, contains potentially toxic compounds like aconitine, which are detoxified during preparation using traditional methods. Comparative toxicological evaluation of laboratory prepared formulation (F1) and two marketed formulations (F2 and F3) were performed based on their effects on viability of H9c2 cells and after single oral dose administration in mice. Cardioprotective effect of formulations at 25 and 50 mg/kg doses were studied in isoproterenol- (ISO-) induced myocardial infarcted rats.

Stability-indicating HPLC method for simultaneous determination of clidinium bromide and chlordiazepoxide in combined dosage forms.

The study describes development and subsequent validation of a stability indicating reverse-phase high-performance liquid chromatography method for the simultaneous estimation of clidinium bromide (CLI) and chlordiazepoxide (CHLOR) from their combination drug product. Chromatographic separations are performed at ambient temperature on a Phenomenex Luna C(18) (250 mm x 4.6 mm, i.

Preparation and bioavailability assessment of SMEDDS containing valsartan.

A self-microemulsifying drug delivery system (SMEDDS) has been developed to enhance diffusion rate and oral bioavailability of valsartan. The solubility of valsartan was checked in different oils, surfactants, and cosurfactants and ternary phase diagrams were constructed to evaluate the microemulsion domain. The valsartan SMEDDS was prepared using Capmul MCM (oil), Tween 80 (surfactant), and polyethylene glycol 400 (cosurfactant).

Stability-indicating reversed-phase liquid chromatographic methods for the determination of aconitine and piperine in a polyherbal formulation.

Simple and rapid stability-indicating HPLC methods were developed for the individual analysis of aconitine (ACN) and piperine (PIN) in Mahamrutynjaya rasa, an herbal dosage form containing Aconitum ferox, Piper nigrum, and Piper longum in combination. Separation of the ACN from its major and minor degradation products was successfully achieved on a reversed-phase C18 column (250 x 4.6 mm id, 5 microm particle size), with isocratic elution using a mixture of acetonitrile-KH2PO4 buffer (10 mM, pH 8 +/- 0.

Enhancement of oral bioavailability of cilostazol by forming its inclusion complexes.

The study was designed to investigate the effect of cyclodextrins (CDs) on the solubility, dissolution rate, and bioavailability of cilostazol by forming inclusion complexes. Natural CDs like beta-CD, gamma-CD, and the hydrophilic beta-CD derivatives, DM-beta-CD and HP-beta-CD, were used to prepare inclusion complexes with cilostazol. Phase solubility study was carried out and the stability constants were calculated assuming a 1:1 stoichiometry.

Development of a stability-indicating high-performance liquid chromatographic method for the simultaneous determination of alprazolam and sertraline in combined dosage forms.

The objective of the current study was to develop a validated stability-indicating high-performance liquid chromatographic method for alprazolam and sertraline in combined dosage forms. The method was validated by subjecting the drugs to forced decomposition under hydrolysis, oxidation, photolysis, and thermal stress conditions prescribed by the International Conference on Harmonization. The drugs were successfully separated from major and minor degradation products on a reversed-phase C18 column by using 75 mM potassium dihydrogen phosphate buffer (pH 4.

Simultaneous determination of a ternary mixture of doxylamine succinate, pyridoxine hydrochloride, and folic acid by the ratio spectra-zero-crossing, double divisor-ratio spectra derivative, and column high-performance liquid chromatographic methods.

Three simple, rapid, and accurate methods, i.e., the derivative ratio spectra-zero-crossing method (method I), double divisor-ratio spectra derivative method (method II), and column reversed-phase high-performance liquid chromatographic (RP-HPLC) method (method III) were developed for the simultaneous determination of doxylamine succinate (DOX), pyridoxine hydrochloride (PYR), and folic acid (FA) in their ternary mixtures and in tablets.