A Two-Way Proposal for the Determination of Bioequivalence for Narrow Therapeutic Index Drugs in the European Union.

In the European Union, bioequivalence (BE) for narrow therapeutic index (NTI) drugs is currently demonstrated when the 90% confidence interval for the ratio of the population geometric means of the test and reference products for AUC, and in some cases for Cmax, falls within the acceptance range of 90.00% to 111.11%.

Isolation of bluish anthocyanin-derived pigments obtained from blueberry surplus using centrifugal partition chromatography.

Replacement of synthetic colorants with natural ones is a current marketing trend. Nevertheless, the naturally occurring blue color is rare compared to other colours. In this work, centrifugal partition chromatography (CPC) process was developed as a more efficient and sustainable alternative to reversed phase column chromatography (RP-CC) for the preparative-scale purification of portisins.

Evaluation of a Proposed Approach for the Determination of the Bioequivalence Acceptance Range for Narrow Therapeutic Index Drugs in the European Union.

Bioequivalence (BE) of products containing narrow therapeutic index (NTI) drugs in the European Union is currently established by demonstrating that the 90% confidence interval for the ratio of the population geometric means of the test compared to the reference product’s AUC, and in certain cases Cmax, is included within the tighter acceptance range of 90.00−111.11%.

Bark as an Antidiabetic Agent.

L. is used throughout the world to treat type 2 diabetes. In Portugal, a traditional herbal preparation made with stem bark of this species (AoBTHP) has been used for more than 30 years to treat this pathology.

A Proposed Approach for the Determination of the Bioequivalence Acceptance Range for Narrow Therapeutic Index Drugs in the European Union.

The current regulatory criterion for bioequivalence of narrow therapeutic index (NTI) drugs in the European Union requires that the 90% confidence interval for the ratio of the population geometric means of the test product compared with the reference for area under the plasma concentration-time curve (AUC), and in certain cases maximum plasma drug concentration (C ), to be included within the tighter acceptance range of 90.00-111.11%.

A mathematical modeling strategy to predict the spreading behavior on skin of sustainable alternatives to personal care emollients.

Spreadability is one of the most important physicochemical properties of cosmetic products, according to the consumer. Thus, it is fundamental to develop strategies with the aim to improve the knowledge and predict the behavior of alternatives to synthetic emollients. The main goal of this research article was to correlate different physicochemical attributes, namely spreading value, apparent viscosity, density, saponification value, iodine value, peroxide value, acid value and melting range, with the spreading behavior of sustainable alternatives for petrolatum and dimethicone.

Starch-Based Pickering Emulsions as Platforms for Topical Antibiotic Delivery: In Vitro and In Vivo Studies.

The present study investigated a new approach to treat superficial skin infections by topical application of minocycline hydrochloride (MH) formulated in a novel starch-based Pickering emulsion (ASt-emulsions). The emulsions were fully characterized in terms of efficacy, as well as in vitro release and permeation studies. The emulsions provided a prolonged MH release, always above its minimum inhibitory concentration against , although the drug did not permeate through the entire skin layer.

Evaluation of dissolution profile similarity - Comparison between the f, the multivariate statistical distance and the f bootstrapping methods.

A simulation study is presented, evaluating the performance of the f, the model-independent multivariate statistical distance and the f bootstrap methods in the ability to conclude similarity between two dissolution profiles. Different dissolution profiles, based on the Noyes-Whitney equation and ranging from theoretical f values between 100 and 40, were simulated. Variability was introduced in the dissolution model parameters in an increasing order, ranging from a situation complying with the European guidelines requirements for the use of the f metric to several situations where the f metric could not be used anymore.

Evading P-glycoprotein mediated-efflux chemoresistance using Solid Lipid Nanoparticles.

Multidrug resistance (MDR), whereby cancer cells become resistant to the cytotoxic effects of various structurally and mechanistically unrelated chemotherapeutic agents, is a major problem in the clinical treatment of cancer. P-glycoprotein (P-gp) is a transmembrane protein responsible for drug efflux, which decreases drug intracellular bioavailability, consequently decreasing their efficacy against cancer. Solid Lipid Nanoparticles (SLNs) have not only the ability to protect the entrapped drug against proteolytic degradation, but also allow a selective intracellular targeting.

Self-assembly PEGylation assists SLN-paclitaxel delivery inducing cancer cell apoptosis upon internalization.

In past years, a considerable progress has been made in the conversion of conventional chemotherapy into potent and safe nanomedicines. The ultimate goal is to improve the therapeutic window of current chemotherapeutics by reducing systemic toxicities and to deliver higher concentrations of the chemotherapeutic agents to malignant cells. In this work, we report that PEGylation of the nanocarriers increases drug intracellular bioavailability leading therefore to higher therapeutic efficacy.

Melatonin-based pickering emulsion for skin's photoprotection.

Context: Based on its antioxidant activity, melatonin was recently found to have a protection effect against photocarcinogenesis.

Objective: This work aimed to develop an innovative sunscreen formulation based on the Pickering emulsions concept, stabilized by physical UV filters, modified starch and natural oils associated to melatonin as a key strategy for prevention against UV-induced skin damage.

Materials And Methods: For this purpose, melatonin was incorporated in Pickering emulsions that were characterized using physicochemical, in vitro and in vivo testing.

Prediction of drug distribution in rat and humans using an artificial neural networks ensemble and a PBPK model.

Purpose: To develop a QSAR model, based on calculated molecular descriptors and an Artificial Neural Networks Ensemble (ANNE), for the estimation of rat tissue-to-blood partition coefficients (Kt:b), as well as the assessment of the applicability domain of the model and its utility in predicting the drug distribution in humans.

Methods: A total of 1460 individual Kt:b values (75% train and 25% validation), obtained in 13 different rat tissues were collected in the literature. A correlation between simple molecular descriptors for lipophilicity, ionization, size and hydrogen bonding capacity and Kt:b data was attempted by using an ANNE.

Tissue-to-blood distribution coefficients in the rat: utility for estimation of the volume of distribution in man.

A compilation of rat tissue-to-blood partition coefficient data obtained both in vitro and in vivo in thirteen different tissues for a total of 309 different drugs is presented. An evaluation of the relationship between several fundamental physicochemical molecular descriptors and these distribution parameters was made. In addition, the ability to predict the Human Volume of distribution by regression analysis and by a Physiologically-based approach was also tested.

Experimental design towards an optimal lipid nanosystem: a new opportunity for paclitaxel-based therapeutics.

Lipid based nanoparticles represent a class of nanocarriers that have caused great expectation, particularly due to their suitability to incorporate BCS class II and IV drugs. The use of solid lipid nanoparticles (SLNs) as a nanocarrier for antineoplastic agents has been underexplored when compared to the encapsulation of the same agents in polymeric particles. The preparation and efficacy assessment of a SLN platform as drug delivery carrier for anticancer agents, herein proposed as a strategy to find innovative formulations, could dramatically improve the outcome of cancer therapy.

Prediction of the human oral bioavailability by using in vitro and in silico drug related parameters in a physiologically based absorption model.

Estimates of the human oral absolute bioavailability were made by using a physiological-based pharmacokinetic model of absorption and the drug solubility at the gastrointestinal pH range 1.5-7.5, the apparent permeability (P(app)) in Caco-2 cells and the intrinsic clearance (Cl(int)) in human hepatocytes suspensions as major drug related parameters.

An alternative single dose parameter to avoid the need for steady-state studies on oral extended-release drug products.

Use of single and multiple-dose studies is required to establish the bioequivalence between two extended-release oral dosage forms under the current European Guidelines. However, FDA is less strict in this regard and only requires a single-dose study. The objective of this work is to use a computer simulation in order to test the two approaches.

Prediction of the in vitro permeability determined in Caco-2 cells by using artificial neural networks.

Caco-2 cells are currently the most used in vitro tool for prediction of the potential oral absorption of new drugs. The existence of computational models based on this data may potentiate the early selection process of new drugs, but the current models are based on a limited number of cases or on a reduced molecular space. We present an artificial neural network based only on calculated molecular descriptors for modelling 296 in vitro Caco-2 apparent permeability (P(app)) drug values collected in the literature using also a pruning procedure for reducing the descriptors space.

Prediction of the in vitro intrinsic clearance determined in suspensions of human hepatocytes by using artificial neural networks.

Use of in vitro suspensions of human hepatocytes is currently accepted as one of the most promising tools for prediction of metabolic clearance in new drugs. The possibility of creating computational models based on this data may potentiate the early selection process of new drugs. We present an artificial neural network for modelling human hepatocyte intrinsic clearances (CL(int)) based only on calculated molecular descriptors.

Prediction of drug distribution within blood.

Drug distribution in blood, defined as drug blood-to-plasma concentration ratio (R(b)), is a fundamental pharmacokinetic parameter. It relates the plasma clearance to the blood clearance, enabling the physiological interpretation of this parameter. Although easily experimentally determined, R(b) values are lacking for the vast majority of drugs.

Lymphatic uptake of pulmonary delivered radiolabelled solid lipid nanoparticles.

Unlabelled: Lymphatic drainage plays an important role in the uptake of particulates in the respiratory system, being also associated to the spreading of lung cancer through metastasis development. In recent years solid lipid nanoparticles (SLN) have been proposed as carriers of anti-tumoural drugs, for their low toxicity and surface characteristics make them suitable for either imaging (gamma-scintigraphy) or therapy upon encapsulation of cytotoxic drugs. Assessment of inhaled radiolabelled SLN biodistribution is described in the present work.