In vitro-in vivo correlation for nevirapine extended release tablets.

An in vitro-in vivo correlation (IVIVC) for four nevirapine extended release tablets with varying polymer contents was developed. The pharmacokinetics of extended release formulations were assessed in a parallel group study with healthy volunteers and compared with corresponding in vitro dissolution data obtained using a USP apparatus type 1. In vitro samples were analysed using HPLC with UV detection and in vivo samples were analysed using a HPLC-MS/MS assay; the IVIVC analyses comparing the two results were performed using WinNonlin.

Miscibility/stability considerations in binary solid dispersion systems composed of functional excipients towards the design of multi-component amorphous systems.

The correlations between amorphous miscibility/physical stability of binary solid dispersions (a highly crystalline additive-an amorphous polymer) and the physicochemical properties of the components were investigated. Crystalline functional excipients including surfactants, organic acids, and organic bases were prepared in binary solid dispersions in amorphous polymers by solvent evaporation method. Amorphous miscibility and physical stability of the systems were characterized using polarized light microscope, differential scanning calorimeter, and powder X-ray diffraction.

Drug-excipient complexation in lipid based delivery systems: an investigation of the Tipranavir-1,3-dioctanolyglycerol complex.

This report describes the solubility properties of a poorly soluble drug-excipient complex in a lipid based formulation. Tipranavir (TPV) was used as the model drug and 1,3-dioctanoylglycerol (DOG) as the excipient. The TPV-DOG complex was prepared by dissolving TPV and DOG in ethanol at 60 degrees C followed by evaporation of ethanol.

Different measures of molecular mobility: comparison between calorimetric and thermally stimulated current relaxation times below Tg and correlation with dielectric relaxation times above Tg.

Stability of the amorphous state has been linked to molecular mobility of the matrix; however different techniques may capture different mobility substates. Our previous work suggested that two calorimetric techniques, Isothermal Microcalorimetry (TAM) and MDSC, measured different aspects of mobility with TAM measuring, in part, some faster modes of relaxation in addition to the modes mobilized at T(g). The aim of this work is to compare the relaxation times obtained using Thermally Stimulated Depolarization Current Spectroscopy (TSDC) with calorimetric mobility measured below T(g) and to determine if all measures of relaxation times below T(g) are consistent with relaxation times obtained above T(g) using Dielectric Spectroscopy (DRS).

Prediction of onset of crystallization from experimental relaxation times. II. Comparison between predicted and experimental onset times.

Unlabelled: Given a good correlation between onsets of crystallization and mobility above T(g), one might be able to predict crystallization onsets at a temperature of interest far below T(g) from this correlation and measurement of mobility at a temperature below T(g). Such predictions require that: (a) correlation between crystallization onset and mobility is the same above and below T(g), and (b) techniques used to measure mobility above and below T(g) measure the same kind of mobility [(b) demonstrated previously using dielectric and calorimetric techniques]. The objective of present work is to determine whether crystallization onset times couple with relaxation times determined above T(g), and if so to verify predictions made below T(g) (from data above T(g)) with experimental data.

Factors affecting the formation of eutectic solid dispersions and their dissolution behavior.

The objective of this work was to obtain a fundamental understanding of the factors, specifically the properties of poorly water-soluble drugs and water-soluble carriers, which influence predominantly, the formation of eutectic or monotectic crystalline solid dispersion and their dissolution behavior. A theoretical model was applied on five poorly water-soluble drugs (fenofibrate, flurbiprofen, griseofulvin, naproxen, and ibuprofen) having diverse physicochemical properties and water-soluble carrier (polyethylene glycol (PEG) 8000) for the evaluation of these factors. Of these, two drugs, fenofibrate and flurbiprofen, and PEG of different molecular weights (3350, 8000, and 20000), were chosen as model drugs and carriers for further investigation.

Predictions of onset of crystallization from experimental relaxation times I-correlation of molecular mobility from temperatures above the glass transition to temperatures below the glass transition.

Purpose: Predicting onsets of crystallization at temperatures below T (g), from data above T (g), would require that the correlation between crystallization onset and mobility is same above and below T (g), and the techniques being used to measure mobility above and below T (g) are measuring essentially the same kind of mobility. The aim of this work is to determine if the relaxation times obtained using different techniques (DSC, TAM) below T (g) correlate with relaxation time obtained above T (g) using dielectric spectroscopy.

Methods: Model compounds for this work were chosen based on their varied DeltaH (f), DeltaC (p)(T (g)) and H-bonding in crystalline state vs.

A mechanistic investigation of an amorphous pharmaceutical and its solid dispersions, part II: molecular mobility and activation thermodynamic parameters.

Purpose: The ability of TSDC to characterize further amorphous materials beyond that possible with DSC was presented in part I (16) of this work. The purpose of part II presented here is to detect and quantitatively characterize time-scales of molecular motions (relaxation times) in amorphous solids at and below the glass transition temperature, to determine distributions of relaxation times associated with different modes of molecular mobility and their temperature dependence, and to determine experimentally the impact upon these parameters of combining the drug with excipients (i.e.

A mechanistic investigation of an amorphous pharmaceutical and its solid dispersions, part I: a comparative analysis by thermally stimulated depolarization current and differential scanning calorimetry.

Purpose: To explore using thermally stimulated depolarization current (TSDC), in comparison to differential scanning calorimetry (DSC), for the characterization of molecular mobility of an amorphous pharmaceutical new chemical entity (LAB687), an amorphous polymer (PVPK-30), and their combination as solid dispersions at different % drug loadings.

Methods: Amorphous drug was prepared by quenching from the melt. Solid dispersions containing 10-60% of drug in polymer were prepared by solvent evaporation method.

Ritonavir-PEG 8000 amorphous solid dispersions: in vitro and in vivo evaluations.

Ritonavir is a large, lipophilic molecule that is practically insoluble in aqueous media and exhibits an exceedingly slow intrinsic dissolution rate. Although it has favorable lipophilicity, in vitro permeability studies have shown that ritonavir is a substrate of P-glycoprotein. Thus, the oral absorption of ritonavir could be limited by both dissolution and permeability, thereby making it a Class IV compound in the Biopharmaceutics Classification System.

Properties of rapidly dissolving eutectic mixtures of poly(ethylene glycol) and fenofibrate: the eutectic microstructure.

Poly(ethylene glycol) or PEG is an ideal inactive component for preparing simple binary eutectic mixtures because of its low entropy of fusion ( approximately 0.0076 J/mol-K), lower melting point (approximately 62 degrees C) compared to most pharmaceuticals, miscibility with drugs at elevated temperatures, and its covalent crystalline lattice. Implication of these physicochemical properties on eutectic crystallization and size reduction of the drug is discussed.