Solid lipid nanoparticles for increased oral bioavailability of acalabrutinib in chronic lymphocytic leukaemia.

Acalabrutinib (ACP) is a first-line treatment for chronic lymphocytic leukemia but suffers from poor and variable oral bioavailability due to its pH-dependent solubility, CYP3A4 metabolism, and P-gp efflux. Thus, the objective of this study was to improve the solubility and dissolution behaviour, in turn enhancing bioavailability, by formulating solid lipid nanoparticles (SLNs). ACP loaded SLNs (ACP-SLNs) were prepared via solvent-free hot emulsification followed by a double sonication process.

Design, pharmacokinetic, and pharmacodynamic evaluation of a lecithin-chitosan hybrid nanoparticle-loaded dual-responsive in situ gel of nebivolol for effective treatment of glaucoma.

In this research work, optimized nebivolol-loaded lecithin-chitosan hybrid nanoparticles (NEB-LCNPs) were prepared using sequential screening and optimization designs. The design of experiments software (DoE) was used to obtain a robust formulation that can improve ocular delivery of the NEB in the treatment of glaucoma. The optimized NEB-LCNPs had a mean particle size of 170.

Design and Evaluation of Clove Oil-Based Self-Emulsifying Drug Delivery Systems for Improving the Oral Bioavailability of Neratinib Maleate.

Neratinib maleate (NM), a tyrosine kinase inhibitor, is used in the treatment of breast cancer. NM is orally administered at a high dose of 290 mg due to its low solubility and poor dissolution rate at pH > 3, as well as gut-wall metabolism limiting its bioavailability. Self-emulsifying drug delivery systems (SEDDSs) of NM were developed in the current study to improve its oral bioavailability.

Nebivolol Polymeric Nanoparticles-Loaded In Situ Gel for Effective Treatment of Glaucoma: Optimization, Physicochemical Characterization, and Pharmacokinetic and Pharmacodynamic Evaluation.

Nebivolol hydrochloride (NEB), a 3rd-generation beta-blocker, was recently explored in managing open-angle glaucoma due to its mechanism of action involving nitric oxide release for the vasodilation. To overcome the issue of low ocular bioavailability and the systemic side effects associated with conventional ocular formulation (aqueous suspension), we designed and optimized polycaprolactone polymeric nanoparticles (NEB-PNPs) by applying design of experiments (DoE). The particle size and drug loading of the optimized NEB-PNPs were 270.

Design, optimization, in vitro and in vivo evaluation of triamcinolone acetonide nanocrystals loaded in situ gel for topical ocular delivery.

Triamcinolone acetonide (TAA), a long-acting synthetic glucocorticoid, is commonly used for the management of posterior uveitis (PU) because of its anti-inflammatory and immunosuppressive characteristics. The commercially available formulation is in the suspension form advised for intravitreal injection, which has a number of serious problems. In the present research work, we prepared TAA nanocrystals (TAA-NCs) using the principles of design of experiments (DoE).

Optimization of a HPLC-UV bioanalytical method using Box-Behnken design to determine the oral pharmacokinetics of neratinib maleate in Wistar rats.

The current research work reports the development and validation of a sensitive, robust and reproducible bioanalytical method for quantifying neratinib maleate in rat plasma. More than 85% of the drug was extracted from the plasma samples by protein precipitation. The method was optimized using Box-Behnken design, a response surface method.

Design, Characterization and Pharmacokinetic-Pharmacodynamic Evaluation of Poloxamer and Kappa-Carrageenan-Based Dual-Responsive In Situ Gel of Nebivolol for Treatment of Open-Angle Glaucoma.

This study developed a dual-responsive in situ gel of nebivolol (NEB), a selective β-adrenergic antagonist. The gel could achieve sustained concentrations in the aqueous humor to effectively treat glaucoma. The gel was prepared using a combination of poloxamers (Poloxamer-407 (P407) and Poloxamer-188 (P188)) and kappa-carrageenan (κCRG) as thermo-responsive and ion-sensitive polymers, respectively.

Optimization and in vivo evaluation of triamcinolone acetonide loaded in situ gel prepared using reacted tamarind seed xyloglucan and kappa-carrageenan for ocular delivery.

In the current work, triamcinolone acetonide (TAA) loaded dual responsive in situ gelling system was designed and optimized using reacted tamarind seed xyloglucan (RXG) (thermoresponsive) and kappa-Carrageenan (κ-CRG) (ion-sensitive) polymers. Tamarind seed xyloglucan (TSX) was subjected to purification followed by enzymatic treatment to produce RXG with ~40 % reduction in galactose content compared to TSX. RXG was characterized using size exclusion chromatography, Fourier transform infrared and proton nuclear magnetic resonance spectroscopy to confirm the ~40 % reduction in galactoside content compared to TSX.

Design and evaluation of rufinamide nanocrystals loaded thermoresponsive nasal gelling system for improved drug distribution to brain.

Rufinamide (Rufi) is an antiepileptic drug used to manage Lennox-Gastaut Syndrome and partial seizures. The oral bioavailability of Rufi is less due to its poor solubility and low dissolution rate in the gastrointestinal fluids. This results in less amount of drug reaching the brain following the oral administration of drug.

UGT1A1 and UGT1A3 activity and inhibition in human liver and intestinal microsomes and a recombinant UGT system under similar assay conditions using selective substrates and inhibitors.

enzyme kinetics and inhibition data was compared for UGT1A1 and UGT1A3 isoforms under similar assay conditions using human liver microsomes (HLM), human intestinal microsomes (HIM) and recombinant UGT (rUGT) enzyme systems.UGT1A1 catalysed β-estradiol 3-β-D-glucuronide formation showed allosteric sigmoidal kinetics in all enzyme systems; while UGT1A3 catalysed CDCA 24-acyl-β-D-glucuronide formation exhibited Michaelis-Menten kinetics in HLM, substrate inhibition kinetics in HIM and rUGT systems. Corresponding or concentrations of β-estradiol and CDCA were employed in the respective UGT inhibition studies.

Dose identification of triamcinolone acetonide for noninvasive pre-corneal administration in the treatment of posterior uveitis using a rapid, sensitive HPLC method with photodiode-array detector.

Triamcinolone acetonide (TAA) is the drug of choice in the management of ocular inflammations due to its anti-inflammatory and immuno-suppressant activity. Available marketed formulations (Triesence, Trivaris, Kenalog) are in the suspension form recommended to be administered via intravitreal injection, which has many major complications. In the present study, we have designed and evaluated Hydroxypropyl-β-cyclodextrin (HP-β-CD),) based conventional formulations of TAA (aqueous suspensions) with different dose strengths to identify the dose strength required for achieving the effective concentrations in vitreous humor following pre-corneal administration of the formulations.

Design and evaluation of thermo-responsive nasal in situ gelling system dispersed with piribedil loaded lecithin-chitosan hybrid nanoparticles for improved brain availability.

Piribedil (PBD) is a compound that has shown efficacy in clinical trials to treat motor and non-motor symptoms of Parkinson's disease. However, drug delivery issues like low oral bioavailability, high dosing frequency (3-5 tablets/day), gastrointestinal side-effects reduced the clinical use of PBD. In this work, we have developed lecithin-chitosan hybrid nanoparticles (PBD-LCNs) to improve the direct nose to brain uptake of PBD.

Design, optimization and pharmacokinetic evaluation of Piribedil loaded solid lipid nanoparticles dispersed in nasal in situ gelling system for effective management of Parkinson's disease.

Piribedil (PBD) is an anti-Parkinson's drug that gained interest recently due to its unique pharmacological profile. But its clinical use is severely limited by drug delivery issues like high dosing frequency (up to 5 tablets/day), low oral bioavailability (<10%), severe GI side-effects, etc. In this work, we have developed solid lipid nanoparticles (PBD-SLNs) to access the nose to brain pathways for direct uptake of PBD.

Rufinamide-Loaded Chitosan Nanoparticles in Xyloglucan-Based Thermoresponsive Gel for Direct Nose to Brain Delivery.

In 2004, the US FDA approved Rufinamide, an anti-epileptic drug under the brand name Banzel. In 2015, Banzel received approval for its use in pediatric patients (ages 1-4 years). Rufinamide shows low oral bioavailability due to a low dissolution rate resulting in less of the drug reaching the brain.

Cilnidipine loaded poly (ε-caprolactone) nanoparticles for enhanced oral delivery: optimization using DoE, physical characterization, pharmacokinetic, and pharmacodynamic evaluation.

Cilnidipine (CND), an anti-hypertensive drug, possesses low oral bioavailability due to its poor aqueous solubility, low dissolution rate, and high gut wall metabolism. In the present study, an attempt has been made to prepare CND loaded polycaprolactone based nanoparticles (CND-PCL-NPs) by nanoprecipitation method applying the concepts of Design of Experiments. Critical factors affecting particle size and loading efficiency (LE%) were assessed by a hybrid design approach, comprising of Mini Run Resolution IV design followed by Box-Behnken design.

Self-assembled lecithin-chitosan nanoparticles improve the oral bioavailability and alter the pharmacokinetics of raloxifene.

In this study, we report the development and evaluation of soy lecithin-chitosan hybrid nanoparticles to improve the oral bioavailability of raloxifene hydrochloride. The nanoparticles were formed by interaction of negatively charged soy lecithin with positively charged chitosan. The ratio of soy lecithin to chitosan was critical for the charge, and hence the size of the nanoparticles.

Piribedil loaded thermo-responsive nasal in situ gelling system for enhanced delivery to the brain: formulation optimization, physical characterization, and in vitro and in vivo evaluation.

Methyl cellulose (MC) based nasal in situ gels were developed to enhance the brain delivery of piribedil (PBD), an anti-Parkinson's drug. Different grades of MC and several solutes (NaCl, KCl, Na.Citrate, STPP, PEG-6000, sucrose, etc.

Oral Bioavailability Enhancement of Raloxifene with Nanostructured Lipid Carriers.

Raloxifene hydrochloride (RLX) shows poor bioavailability (<2%), high inter-patient variability and extensive gut metabolism (>90%). The objective of this study was to develop nanostructured lipid carriers (NLCs) for RLX to enhance its bioavailability. The NLC formulations were produced with glyceryl tribehenate and oleic acid.

Pharmacodynamic, pharmacokinetic and physical characterization of cilnidipine loaded solid lipid nanoparticles for oral delivery optimized using the principles of design of experiments.

Cilnidipine (CND), an anti-hypertensive drug, is known to have low oral bioavailability due to its poor aqueous solubility, low dissolution rate and high gut wall metabolism. In the present study, CND loaded compritol based nanoparticles (CND-CMP-NPs) were prepared by emulsification-solvent evaporation method applying the concepts of design of experiments. Critical factors affecting particle size and loading efficiency (LE%) were assessed by hybrid design approach, comprising of Mini Run Resolution IV design followed by Box-Behnken design.

Comparative study of cilnidipine loaded PLGA nanoparticles: process optimization by DoE, physico-chemical characterization and in vivo evaluation.

Cilnidipine (CND) is known to have low oral bioavailability due to its poor aqueous solubility, low dissolution rate, and high gut wall metabolism. In the present study, CND-loaded PLGA nanoparticles (CND-PLGA-NPs) were prepared with two different grades of PLGA (50:50 and 75:25) by design of experiment. Critical factors affecting particle size and entrapment efficiency (EE%) were assessed by mixed design approach, comprising of Plackett-Burman design followed by rotatable central composite design.

Development and validation of a bio-analytical method for simultaneous quantification of nebivolol and labetalol in aqueous humor and plasma using LC-MS/MS and its application to ocular pharmacokinetic studies.

Beta blockers is the class of choice of drugs in treatment of open angle Glaucoma. However, many of these drugs suffer from systemic side effects due to their absorption into systemic circulation via nasolachrymal duct. To evaluate the safety and efficacy of nebivolol and labetalol for the treatment of open angle glaucoma, it is important to have a bioanalytical method for measuring the drug concentrations both in aqueous humor and plasma.

Apoptosis-Mediated Cytotoxic Effect of var. on Colon (HT29) and Hepatic (HepG2) Cancer Cell Lines.

Introduction: var. (Wight) Grav. and Mayur.

Design of experiments-based RP - HPLC bioanalytical method development for estimation of Rufinamide in rat plasma and brain and its application in pharmacokinetic study.

This study reports a fully validated HPLC-UV (High Performance Liquid Chromatography- Ultra Violet) method for quantitative estimation of Rufinamide (RUFI), an antiepileptic drug, in rat plasma and brain matrices. A response surface methodology based Box Behnken experimental design, using the principles of Design of Experiments (DoE), was employed to optimize critical chromatographic conditions viz. pH and proportion of the buffer and wavelength of detection, for achieving good sensitivity (peak area) and specificity (number of theoretical plates).

Development and validation of rapid and sensitive LC methods with PDA and fluorescence detection for determination of piribedil in rat plasma and brain tissues and their pharmacokinetic application.

Simple, selective and sensitive high-performance liquid chromatographic (HPLC) bioanalytical methods using fluorescence (FL) and photodiode array (PDA) detectors were developed and validated for determination of piribedil (PBD), an anti-Parkinson's drug, in rat plasma and brain samples, with telmisartan as internal standard (IS). Protein precipitation technique was used to extract PBD from both biological matrices. Chromatographic separation was achieved on a Phenomenex Kinetex C end-capped column (250 × 4.