Wayne Matthews | GlaxoSmithKline, LLP (original) (raw)

Papers by Wayne Matthews

Research paper thumbnail of Biorelevant intrinsic dissolution profiling in early drug development: Fundamental, methodological, and industrial aspects

European Journal of Pharmaceutics and Biopharmaceutics, 2019

Intrinsic dissolution rate (IDR) is the surface specific dissolution rate of a drug. In early dru... more Intrinsic dissolution rate (IDR) is the surface specific dissolution rate of a drug. In early drug development, this property (among other parameters) is measured in order to compare different polymorphs and salt forms, guide formulation decisions, and to provide a quality marker of the active pharmaceutical ingredient (API) during production. In this review, an update on different methods and small-scale techniques that have recently evolved for determination of IDR is provided. The importance of biorelevant media and the hydrodynamic conditions of dissolution are also discussed. Different preparation techniques for samples are presented with a focus on disc, particle-and crystal-based methods. A number Bergström, C.A.S. Intrinsic dissolution profiling in early drug development 5 (49)

Research paper thumbnail of Investigation of the intra- and inter-laboratory reproducibility of a small scale standardized supersaturation and precipitation method

Molecular pharmaceutics, Dec 18, 2017

The high number of poorly water soluble compounds in drug development has increased the need for ... more The high number of poorly water soluble compounds in drug development has increased the need for enabling formulations to improve oral bioavailability. One frequently applied approach is to induce supersaturation at the absorptive site, e.g. the small intestine, increasing the amount of dissolved compound available for absorption. However, due to the stochastic nature of nucleation, supersaturating drug delivery systems may lead to inter- and intrapersonal variability. The ability to define a feasible range with respect to the supersaturation level is a crucial factor for a successful formulation. Therefore, an in vitro method is needed, from where the ability of a compound to supersaturate can be defined in a reproducible way. Hence, this study investigates the reproducibility of an in vitro small scale Standardized Supersaturation and Precipitation Method (SSPM). First an intra-laboratory reproducibility study of felodipine was conducted, after which seven partners contributed wit...

Research paper thumbnail of Identification and characterisation of a salt form of Danirixin with reduced pharmacokinetic variability in patient populations

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, Jan 3, 2017

The natural variability of gastric pH or gastric acid reducing medications can result in lower an... more The natural variability of gastric pH or gastric acid reducing medications can result in lower and more variable clinical pharmacokinetics for basic compounds in patient populations. Progressing alternative salt forms with improved solubility and dissolution properties can minimise this concern. This manuscript outlines a nonclinical approach comprising multiple biopharmaceutical, in vitro and physiologically based pharmacokinetic model (PBPK) modelling studies to enable selection of an alternative salt form for danirixin (DNX, GSK1325756), a pharmaceutical agent being developed for chronic obstructive pulmonary disease (COPD). The hydrobromide salt of DNX was identified as having superior biopharmaceutical properties compared to the free base (FB) form in clinical development and the impact of switching to the hydrobromide salt (HBr) was predicted by integrating the nonclinical data in a PBPK model (using GastroPlus™) to enable simulation of clinical drug exposure with FB and HBr s...

Research paper thumbnail of Application of QbD Principles for the Evaluation of Empty Hard Capsules as an Input Parameter in Formulation Development and Manufacturing

AAPS PharmSciTech, 2014

Understanding the product and process variable on the final product performance is an essential p... more Understanding the product and process variable on the final product performance is an essential part of the quality-by-design (QbD) principles in pharmaceutical development. The hard capsule is an established pharmaceutical dosage form used worldwide in development and manufacturing. The empty hard capsules are supplied as an excipient that is filled by pharmaceutical manufacturers with a variety of different formulations and products. To understand the potential variations of the empty hard capsules as an input parameter and its potential impact on the finished product quality, a study was performed investigating the critical quality parameters within and in between different batches of empty hard gelatin capsules. The variability of the hard capsules showed high consistency within the specification of the critical quality parameters. This also accounts for the disintegration times, when automatic endpoint detection was used. Based on these data, hard capsules can be considered as ...

Research paper thumbnail of An interlaboratory investigation of intrinsic dissolution rate determination using surface dissolution

European Journal of Pharmaceutics and Biopharmaceutics, 2020

The purpose of this study was to conduct an interlaboratory ring-study, with six partners (academ... more The purpose of this study was to conduct an interlaboratory ring-study, with six partners (academic and industrial), investigating the measurement of intrinsic dissolution rate (IDR) using surface dissolution imaging (SDI) equipment. Measurement of IDR is important in pharmaceutical research as it provides characterising information on drugs and their formulations. This work allowed us to assess the SDI's interlaboratory performance for measuring IDR using a defined standard operating procedure (see supporting information) and six drugs assigned as low (tadalafil, bromocriptine mesylate), medium (carvedilol, indomethacin) and high (ibuprofen, valsartan) solubility compounds. Fasted State Simulated Intestinal Fluid (FaSSIF) and blank FaSSIF (without sodium taurocholate and lecithin) (pH 6.5) were used as media. Using the standardised protocol an IDR value was obtained for all compounds and the results show that the overall IDR rank order matched the solubility rank order. Interlaboratory variability was also examined and it was observed that the variability for lower solubility compounds was higher, coefficient of variation > 50%, than for intermediate and high solubility compounds, with the exception of indomethacin in FaSSIF medium. Inter laboratory variability is a useful descriptor for understanding the robustness of the protocol and the system variability. On comparison to another published small-scale IDR study the rank ordering with respect to dissolution rate is identical except for the high solubility compounds. This results indicates that the SDI robustly measures IDR however, no recommendation on the use of one small scale method over the other is made.

Research paper thumbnail of Biorelevant intrinsic dissolution profiling in early drug development: Fundamental, methodological, and industrial aspects

European Journal of Pharmaceutics and Biopharmaceutics, 2019

Intrinsic dissolution rate (IDR) is the surface specific dissolution rate of a drug. In early dru... more Intrinsic dissolution rate (IDR) is the surface specific dissolution rate of a drug. In early drug development, this property (among other parameters) is measured in order to compare different polymorphs and salt forms, guide formulation decisions, and to provide a quality marker of the active pharmaceutical ingredient (API) during production. In this review, an update on different methods and small-scale techniques that have recently evolved for determination of IDR is provided. The importance of biorelevant media and the hydrodynamic conditions of dissolution are also discussed. Different preparation techniques for samples are presented with a focus on disc, particle-and crystal-based methods. A number Bergström, C.A.S. Intrinsic dissolution profiling in early drug development 5 (49)

Research paper thumbnail of Investigation of the intra- and inter-laboratory reproducibility of a small scale standardized supersaturation and precipitation method

Molecular pharmaceutics, Dec 18, 2017

The high number of poorly water soluble compounds in drug development has increased the need for ... more The high number of poorly water soluble compounds in drug development has increased the need for enabling formulations to improve oral bioavailability. One frequently applied approach is to induce supersaturation at the absorptive site, e.g. the small intestine, increasing the amount of dissolved compound available for absorption. However, due to the stochastic nature of nucleation, supersaturating drug delivery systems may lead to inter- and intrapersonal variability. The ability to define a feasible range with respect to the supersaturation level is a crucial factor for a successful formulation. Therefore, an in vitro method is needed, from where the ability of a compound to supersaturate can be defined in a reproducible way. Hence, this study investigates the reproducibility of an in vitro small scale Standardized Supersaturation and Precipitation Method (SSPM). First an intra-laboratory reproducibility study of felodipine was conducted, after which seven partners contributed wit...

Research paper thumbnail of Identification and characterisation of a salt form of Danirixin with reduced pharmacokinetic variability in patient populations

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, Jan 3, 2017

The natural variability of gastric pH or gastric acid reducing medications can result in lower an... more The natural variability of gastric pH or gastric acid reducing medications can result in lower and more variable clinical pharmacokinetics for basic compounds in patient populations. Progressing alternative salt forms with improved solubility and dissolution properties can minimise this concern. This manuscript outlines a nonclinical approach comprising multiple biopharmaceutical, in vitro and physiologically based pharmacokinetic model (PBPK) modelling studies to enable selection of an alternative salt form for danirixin (DNX, GSK1325756), a pharmaceutical agent being developed for chronic obstructive pulmonary disease (COPD). The hydrobromide salt of DNX was identified as having superior biopharmaceutical properties compared to the free base (FB) form in clinical development and the impact of switching to the hydrobromide salt (HBr) was predicted by integrating the nonclinical data in a PBPK model (using GastroPlus™) to enable simulation of clinical drug exposure with FB and HBr s...

Research paper thumbnail of Application of QbD Principles for the Evaluation of Empty Hard Capsules as an Input Parameter in Formulation Development and Manufacturing

AAPS PharmSciTech, 2014

Understanding the product and process variable on the final product performance is an essential p... more Understanding the product and process variable on the final product performance is an essential part of the quality-by-design (QbD) principles in pharmaceutical development. The hard capsule is an established pharmaceutical dosage form used worldwide in development and manufacturing. The empty hard capsules are supplied as an excipient that is filled by pharmaceutical manufacturers with a variety of different formulations and products. To understand the potential variations of the empty hard capsules as an input parameter and its potential impact on the finished product quality, a study was performed investigating the critical quality parameters within and in between different batches of empty hard gelatin capsules. The variability of the hard capsules showed high consistency within the specification of the critical quality parameters. This also accounts for the disintegration times, when automatic endpoint detection was used. Based on these data, hard capsules can be considered as ...

Research paper thumbnail of An interlaboratory investigation of intrinsic dissolution rate determination using surface dissolution

European Journal of Pharmaceutics and Biopharmaceutics, 2020

The purpose of this study was to conduct an interlaboratory ring-study, with six partners (academ... more The purpose of this study was to conduct an interlaboratory ring-study, with six partners (academic and industrial), investigating the measurement of intrinsic dissolution rate (IDR) using surface dissolution imaging (SDI) equipment. Measurement of IDR is important in pharmaceutical research as it provides characterising information on drugs and their formulations. This work allowed us to assess the SDI's interlaboratory performance for measuring IDR using a defined standard operating procedure (see supporting information) and six drugs assigned as low (tadalafil, bromocriptine mesylate), medium (carvedilol, indomethacin) and high (ibuprofen, valsartan) solubility compounds. Fasted State Simulated Intestinal Fluid (FaSSIF) and blank FaSSIF (without sodium taurocholate and lecithin) (pH 6.5) were used as media. Using the standardised protocol an IDR value was obtained for all compounds and the results show that the overall IDR rank order matched the solubility rank order. Interlaboratory variability was also examined and it was observed that the variability for lower solubility compounds was higher, coefficient of variation > 50%, than for intermediate and high solubility compounds, with the exception of indomethacin in FaSSIF medium. Inter laboratory variability is a useful descriptor for understanding the robustness of the protocol and the system variability. On comparison to another published small-scale IDR study the rank ordering with respect to dissolution rate is identical except for the high solubility compounds. This results indicates that the SDI robustly measures IDR however, no recommendation on the use of one small scale method over the other is made.