brian carlin - Academia.edu (original) (raw)

Papers by brian carlin

Raw material compliance and GMP do not eliminate variability. Quality by Design should minimize t... more Raw material compliance and GMP do not eliminate variability. Quality by Design should minimize the risk that raw material variability will adversely affect the finished product Critical Quality Attributes. The sources of technological risk from excipients are reviewed and approaches to excipient risk management are discussed. Supplier involvement throughout the product life-cycle is recommended to minimize excipient-related risk.

He who knows not and knows not that he knows not is a fool; avoid him. He who knows not and knows... more He who knows not and knows not that he knows not is a fool; avoid him. He who knows not and knows that he knows not is a student; teach him. He who knows and knows not that he knows is asleep; wake him. He who knows and knows that he knows is a wise man; follow him.

Journal of Excipients and Food Chemicals, 2012

Pharmaceutical Quality by Design

A coprocessed particles containing substantially anhydrous coprocessed microcrystalline cellulose... more A coprocessed particles containing substantially anhydrous coprocessed microcrystalline cellulose and at least one polyol, wherein: the ratio of microcrystalline cellulose and at least one polyol is from 99: 1 to 1:99, the "at least" a polyol containing four carbon atoms, and the ratio of the compactability of an unlubricated composition and compactness of a lubricated is 1.9 or less when the lubricated composition additionally comprises 1% of magnesium stearate.

Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms, 2016

Journal of Excipients and Food Chemicals, Mar 30, 2015

European Journal of Pharmaceutics and Biopharmaceutics Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E V, May 1, 2009

The aim of this study was to better understand the underlying drug release mechanisms from aqueou... more The aim of this study was to better understand the underlying drug release mechanisms from aqueous ethylcellulose-coated pellets containing different types of drugs and starter cores. Theophylline, paracetamol, metoprolol succinate, diltiazem HCl and metoprolol tartrate were used as model drugs exhibiting significantly different solubilities (e.g. 14, 19, 284, 662 and 800 mg/mL at 37°C in 0.1 N HCl). The pellet core consisted of a drug matrix, drug-layered sugar bead or drug-layered microcrystalline cellulose (MCC) bead, generating different osmotic driving forces upon contact with aqueous media. Importantly, the addition of small amounts of poly(vinyl alcohol)-poly(ethylene glycol) graft copolymer (PVA-PEG graft copolymer) to the ethylcellulose coatings allowed for controlled drug release within 8-12 h, irrespective of the type of drug and composition of the pellet core. Drug release was found to be controlled by diffusion through the intact polymeric membranes, irrespective of the drug solubility and type of core formulation. The ethylcellulose coating was dominant for the control of drug release, minimizing potential effects of the type of pellet core and nature of the surrounding bulk fluid, e.g. osmolality. Thus, this type of controlled drug delivery system can be used for very different drugs and is robust.

Journal of Excipients and Food Chemicals, Dec 22, 2012

Journal of Excipients and Food Chemicals, Sep 27, 2013

Raw material compliance with compendial specifications, and supply chain integrity, are necessary... more Raw material compliance with compendial specifications, and supply chain integrity, are necessary but insufficient requirements for patient safety. The former ensures the identity of the material, absence of toxic and unsafe components, and fitness for the intended route of administration. The latter ensures that the material has been manufactured and distributed in accordance with Good Manufacturing and Distribution Practices. However, compliance with compendial specifications alone does not guarantee 'excipient pedigree'. As evidenced by the FDA Monograph Modernisation Initiative, for some excipients, compendial ID tests and assays can themselves be inadequate. Neither compliance, nor supply chain integrity, can ensure fitness for purpose in a particular application.

Rational Design and Formulation, 2008

International Journal of Pharmaceutics, 2015

The quality by design (QbD) initiative is promoting a better understanding of excipient performan... more The quality by design (QbD) initiative is promoting a better understanding of excipient performance and the identification of critical material attributes (CMAs). Despite microcrystalline cellulose (MCC) being one of the most popular direct compression binders, only a few studies attempted identifying its CMAs. These studies were based either on a limited number of samples or on MCC produced on a small scale and/or in conditions that deviate from those normally encountered in production. The present work utilizes multivariate analyses first to describe a large database of MCCs produced on a commercial scale, including an overview of their physicochemical properties, and secondly to correlate the most significant material attributes with tabletability. Particle size and moisture content are often considered as the most common if not the sole CMAs with regard to MCC performance in direct compression. The evaluation of more than 80 neat MCCs and the performance of selected samples in a model formulation revealed the importance of other potential critical attributes such as tapped density. Drug product developers and excipient suppliers should work together to identify these CMAs, which may not always be captured by the certificate of analysis.