Poly (vinyl alcohol) microneedles: Fabrication, characterization, and application for transdermal drug delivery of doxorubicin.

Poly (vinyl alcohol) microneedles were fabricated, characterized, and applied to enhance in vitro transdermal delivery of doxorubicin. The microneedles were fabricated using the micromolding technique with the drug load in different locations within the needle array. The polymer solution was assessed for rheological properties, drug dissolution, and chemical structurestudies.

Mesoporous silica-based dosage forms improve bioavailability of poorly soluble drugs in pigs: case example fenofibrate.

Objectives: Mesoporous silicas (SLC) have demonstrated considerable potential to improve bioavailability of poorly soluble drugs by facilitating rapid dissolution and generating supersaturation. The addition of certain polymers can further enhance the dissolution of these formulations by preventing drug precipitation. This study uses fenofibrate as a model drug to investigate the performance of an SLC-based formulation, delivered with hydroxypropyl methylcellulose acetate succinate (HPMCAS) as a precipitation inhibitor, in pigs.

Use of Polyvinyl Alcohol as a Solubility Enhancing Polymer for Poorly Water-Soluble Drug Delivery (Part 2).

The KinetiSol® Dispersing (KSD) technology has enabled the investigation into the use of polyvinyl alcohol (PVAL) as a concentration enhancing polymer for amorphous solid dispersions. Our previous study revealed that the 88% hydrolyzed grade of PVAL was optimal for itraconazole (ITZ) amorphous compositions with regard to solid-state properties, non-sink dissolution performance, and bioavailability enhancement. The current study investigates the influence of molecular weight for the 88% hydrolyzed grades of PVAL on the properties of KSD processed ITZ:PVAL amorphous dispersions.

Enabling thermal processing of ritonavir-polyvinyl alcohol amorphous solid dispersions by KinetiSol® Dispersing.

Polyvinyl alcohol has received little attention as a matrix polymer in amorphous solid dispersions (ASDs) due to its thermal and rheological limitations in extrusion processing and limited organic solubility in spray drying applications. Additionally, in extrusion processing, the high temperatures required to process often exclude thermally labile APIs. The purpose of this study was to evaluate the feasibility of processing polyvinyl alcohol amorphous solid dispersions utilizing the model compound ritonavir with KinetiSol® Dispersing (KSD) technology.

Use of Polyvinyl Alcohol as a Solubility-Enhancing Polymer for Poorly Water Soluble Drug Delivery (Part 1).

Polyvinyl alcohol (PVAL) has not been investigated in a binary formulation as a concentration-enhancing polymer owing to its high melting point/high viscosity and poor organic solubility. Due to the unique attributes of the KinetiSol® dispersing (KSD) technology, PVAL has been enabled for this application and it is the aim of this paper to investigate various grades for improvement of the solubility and bioavailability of poorly water soluble active pharmaceutical ingredients. Solid amorphous dispersions were created with the model drug, itraconazole (ITZ), at a selected drug loading of 20%.

Mesoporous silica-based dosage forms improve release characteristics of poorly soluble drugs: case example fenofibrate.

Objectives: Mesoporous silica-based dosage forms offer the potential for improving the absorption of poorly soluble drugs after oral administration. In this investigation, fenofibrate was used as a model drug to study the ability of monomodal ('PSP A') and bimodal ('PSP B') porous silica to improve release by a 'spring' effect in in vitro biorelevant dissolution tests. Also investigated was the addition of various polymers to provide a 'parachute' effect, that is, to keep the drug in solution after its release.

Chiral capillary liquid chromatography based on penicillin G acylase immobilized on monolithic epoxy silica column.

An epoxy derivatized monolithic silica capillary column (100 μm i.d.) was used as a support for immobilization of penicillin G acylase (PGA), an enzyme used in the production of semisynthetic antibiotics.

Chirally functionalized anion-exchange type silica monolith for enantiomer separation of 2-aryloxypropionic acid herbicides by non-aqueous capillary electrochromatography.

A silica based monolithic capillary column derivatized with O-9-(tert-butylcarbamoyl)quinidine was prepared for CEC enantiomer separation of chiral 2-aryloxypropionic acid herbicides including inter alia dichlorprop, mecoprop and fenoprop. The silica monolith had a relatively low surface coverage with chiral cationic selector moieties. Due to the low selector density retention factors were low as well, yet still enabling enantiomer separations of the target solutes.

Profiling of endogenous peptides by multidimensional liquid chromatography: On-line automated sample cleanup for biomarker discovery in human urine.

A simple and flexible system, employing a column switching technique, has been designed to allow the analysis of peptides and proteins smaller than 15 kDa by molecular weight in filtered urine samples by performing a direct on-column injection utilising simultaneous sample clean-up and trace enrichment. The positively charged peptides and small proteins in the sample are attracted to the inner, negatively charged pore structure of the RAM-SCX column while the larger proteins and uncharged or negatively charged compounds are excluded. After preconditioning with the biological sample, large amounts of sample can be injected.

Normal-phase automated mass-directed HPLC purification of a pyrrolobenzodiazepine library with vasopressin agonist activity.

A 23-member library of pyrrolobenzodiazepine derivatives with vasopressin agonist activity was purified on a 100-mg per injection scale using normal-phase (NP) automated mass-directed HPLC. Analytical NP APCI-LC/MS on an experimental monolith silica CN column utilizing gradients of methanol in ethoxynonafluorobutane (hexane-like solvent) was used to provide data on chromatographic purity and ionization of the solutes. The analytical data collected were used to program a preparative LC/MS instrument for "smart" fraction collection based on the protonated molecular ion of the component of interest.

Deconvolution of electrokinetic and chromatographic contributions to solute migration in stereoselective ion-exchange capillary electrochromatography on monolithic silica capillary columns.

A monolithic silica stationary phase functionalized with an enantioselective strong cation exchanger based on an aminosulfonic acid derivative was used for chiral separations of basic test solutes by nonaqueous CEC and capillary LC. The effects of the applied electric field as well as the ionic strength in the eluent on electrokinetic and chromatographic contributions to the overall separation performance in the electrically driven mode were investigated. Hence, under the utilized experimental conditions, i.

Textural characterization of native and n-alky-bonded silica monoliths by mercury intrusion/extrusion, inverse size exclusion chromatography and nitrogen adsorption.

Native and n-alkyl-bonded (n-octadecyl) monolithic silica rods with mesopores in the range between 10 and 25 nm and macropores in the range between 1.8 and 6.0 microm were examined by mercury intrusion/extrusion, inverse size exclusion chromatography (ISEC) and nitrogen sorption.

Enantioselective silica-based monoliths modified with a novel aminosulfonic acid-derived strong cation exchanger for electrically driven and pressure-driven capillary chromatography.

Silica monoliths modified with trans-(1S,2S)-2-(N-4-allyloxy-3,5-dichlorobenzoyl)amino cyclohexanesulfonic acid were tested for enantioselective separations of various chiral bases by aqueous and nonaqueous CEC as well as nano-HPLC. The optimization of the immobilization procedure showed that an intermediate selector (SO) coverage, as does result from a single static immobilization cycle in the capillary at 60 degrees C with an 8% (m/v) SO solution in methanol, affords maximal EOF and optimal enantioselectivity values, while a second immobilization cycle does not lead to any improvements. Furthermore, the mobile phase composition was examined regarding the effectiveness of aqueous phases (ACN/water and methanol/water) compared to nonaqueous eluents (ACN/methanol) in terms of separation selectivity and efficiency.

Pronase-immobilized enzyme reactor: an approach for automation in glycoprotein analysis by LC/LC-ESI/MSn.

An automated analytical approach is proposed for simultaneous characterization of glycan and peptide moieties in pronase-generated glycopeptides. The proposed method is based on the use of a new pronase-immobilized enzyme reactor for the on-line rapid digestion of the target glycoprotein. By coupling the bioreactor to a Hypercarb chromatographic trap column, on-line selective glycopeptide enrichment prior to normal-phase liquid chromatography-mass spectrometry was obtained.

Monolithic silica columns of various format in automated sample clean-up/multidimensional liquid chromatography/mass spectrometry for peptidomics.

The following particulate and monolithic silica columns were implemented in a fully automated and flexible multidimensional LC/MS system with integrated sample clean-up, to perform the analysis of endogeneous peptides from filtered urine and plasma samples: restricted access sulphonic acid strong cation-exchanger (RAM-SCX) for sample clean-up, RP 18 Chromolith guard columns as trap columns and 100 microm I.D. monolithic RP 18 fused silica capillary columns as last LC dimension.

Pore structural characterization of monolithic silica columns by inverse size-exclusion chromatography.

In this work, a parallel pore model (PPM) and a pore network model (PNM) are developed to provide a state-of-art method for the calculation of several characteristic pore structural parameters from inverse size-exclusion chromatography (ISEC) experiments. The proposed PPM and PNM could be applicable to both monoliths and columns packed with porous particles. The PPM and PNM proposed in this work are able to predict the existence of the second inflection point in the experimental exclusion curve that has been observed for monolithic materials by accounting for volume partitioning of the polymer standards in the macropores of the column.

Impact of pore structural parameters on column performance and resolution of reversed-phase monolithic silica columns for peptides and proteins.

In this work, monolithic silica columns with the C4, C8, and C18 chemistry and having various macropore diameters and two different mesopore diameters are studied to access the differences in the column efficiency under isocratic elution conditions and the resolution of selected peptide pairs under reversed-phase gradient elution conditions for the separation of peptides and proteins. The columns with the pore structural characteristics that provided the most efficient separations are then employed to optimize the conditions of a gradient separation of a model mixture of peptides and proteins based on surface chemistry, gradient time, volumetric flow rate, and acetonitrile concentration. Both the mesopore and macropore diameters of the monolithic column are decisive for the column efficiency.

Stereoselective separations of chiral phosphinic acid pseudodipeptides by CEC using silica monoliths modified with an anion-exchange-type chiral selector.

A nonaqueous CEC method for the simultaneous separation of the four stereoisomers of the N-benzyloxycarbonyl phosphinic pseudodipeptide methyl ester benzyloxycarbonyl-homophenylalanine Z-hPhepsi(PO2HCH2)Phe-OCH3 as well as of the corresponding N-2,4-dinitrophenyl (DNP)-derivative with free C-terminal carboxylic group DNP-hPhepsi(PO2HCH2)Phe-OH was developed. For this purpose, a monolithic silica capillary column modified with a cinchona alkaloid-derived anion-exchange-type chiral selector, namely O-9-(tert-butylcarbamoyl)quinidine (tBuCQD) was prepared. The mobile phase composition (ACN/methanol ratio, counterion type) was thoroughly optimized to end up with baseline resolution of all four stereoisomers with critical resolution of as high as about 2.

Silica-based monolithic columns with mixed-mode reversed-phase/weak anion-exchange selectivity principle for high-performance liquid chromatography.

This article describes the synthesis, chromatographic characterization, and performance evaluation of analytical (100 x 4.6 mm id) and semipreparative (100 x 10 mm id) monolithic silica columns with mixed-mode RP/weak anion-exchange (RP/WAX) surface modification. The monolithic RP/WAX columns were obtained by immobilization of N-(10-undecenoyl)-3-aminoquinuclidine onto thiol-modified monolithic silica columns (Chromolith) by a radical addition reaction.

Sulphonic acid strong cation-exchange restricted access columns in sample cleanup for profiling of endogenous peptides in multidimensional liquid chromatography. Structure and function of strong cation-exchange restricted access materials.

In this work, the pore structural parameters and size exclusion properties of LiChrospher strong cation-exchange and reverse phase restricted access materials (RAM) are analysed. The molecular weight size exclusion limit for polystyrenes was found to be about 17.7 kDa, while for standard proteins, the molecular weight size exclusion limit was higher, at approximately 25 kDa.

Optimization of a trypsin-bioreactor coupled with high-performance liquid chromatography-electrospray ionization tandem mass spectrometry for quality control of biotechnological drugs.

The optimization of a silica-based trypsin bioreactor and its use in the quality control of biotechnological drugs like peptides and proteins is described. Five bioreactors based on monolithic material have been prepared, with different amount of bound trypsin. The performances of these bioreactors were compared to the proteolytic activity of a bioreactor based on silica material.

Fast, high-efficiency peptide separations on a 50-microm reversed-phase silica monolith in a nanoLC-MS set-up.

Proteomic studies have stimulated the development of novel stationary phases in miniaturised chromatographic columns that permit high linear flow velocities and exhibit high resolving power. In this work, a 50-microm reversed-phase silica-based monolith was chromatographically characterised for its use in proteomics applications using a nanoLC-MS set-up. It showed high efficiency for the separation of tryptic peptides under isocratic elution conditions (HETP(min)=5-10 microm at 2.

Monolithic silica-based capillary column with strong chiral cation-exchange type surface modification for enantioselective non-aqueous capillary electrochromatography.

A silica-based monolithic stationary phase prepared by the sol-gel process in a 100 microm I.D. fused-silica (FS) capillary has been modified chemically with 3-mercaptopropyl trimethoxysilane followed by immobilization of a strong cation-exchange (SCX) type chiral selector, (S)-N-(4-allyloxy-3,5-dichlorobenzoyl)-2-amino-3,3-dimethylbutane phosphonic acid, by radical addition reaction onto the reactive sulfhydryl surface.

Making broad proteome protein measurements in 1-5 min using high-speed RPLC separations and high-accuracy mass measurements.

The throughput of proteomics measurements that provide broad protein coverage is limited by the quality and speed of both the separations as well as the subsequent mass spectrometric analysis; at present, analysis times can range anywhere from hours (high throughput) to days or longer (low throughput). We have explored the basis for proteomics analyses conducted on the order of minutes using high-speed capillary RPLC combined through on-line electrospray ionization interface with high-accuracy mass spectrometry (MS) measurements. Short 0.

A silica-based monolithic column in capillary HPLC and CEC coupled with ESI-MS or electrospray-atmospheric-pressure laser ionization-MS.

We describe the successful coupling of CEC and capillary HPLC with the recently developed atmospheric-pressure laser ionization (APLI) method. APLI is suitable for selectively and sensitively ionizing nonpolar aromatic compounds at ambient pressure for subsequent mass-selective detection. The polycyclic aromatic hydrocarbons used as analytes are first separated either by CEC on a silica-based monolithic column or by capillary HPLC.