Chad Dalton

Differential scanning calorimetry: applications in drug development.

Differential scanning calorimetry (DSC) is frequently the pharmaceutical thermal analysis technique of choice because of its ability to provide detailed information about both the physical and energetic properties of a substance. This review provides an up-to-date overview of the applications of DSC in the drug development process. It should serve as a broad introduction to those starting work in this area, and also as a valuable reference for those already practising in this field.

Processing and storage effects on water vapor sorption by some model pharmaceutical solid dosage formulations

Abstract Several excipients and their formulations were equilibrated at relative humidities and temperatures selected to simulate typical pharmaceutical storage and processing conditions. Three different water detection techniques—loss on drying, Karl Fischer coulometry and an automatic moisture balance, were used to determine the moisture content of these systems. The excipients all possessed very different water sorption tendencies, as did their formulations. Isothermal water sorption by the dry blends, granules and tablets of each formulation was identical, suggesting that the processes involved in tablet manufacturing did not affect the water sorption behavior. Accurate water content predictions for the formulations were possible by adding the contribution of water from each excipient. Such predictions may be helpful for defining upper and lower water content specifications and storage conditions for excipients and their formulations.

Discovery of MK-7246, a selective CRTH2 antagonist for the treatment of respiratory diseases

In this manuscript we wish to report the discovery of MK-7246 (4), a potent and selective CRTH2 (DP2) antagonist. SAR studies leading to MK-7246 along with two synthetic sequences enabling the preparation of this novel class of CRTH2 antagonist are reported. Finally, the pharmacokinetic and metabolic profile of MK-7246 is disclosed.

Detection of a Minor Amorphous Phase in Crystalline Etoricoxib by Dynamic Mechanical Analysis: Comparison with Raman Spectroscopy and Modulated Differential Scanning Calorimetry

Detection and quantification of the amorphous phase of etoricoxib bulk drug substances, a selective cycloogenase-2 inhibitor used for the treatment of osteoarthritis, rheumatoid arthritis, and dental pain, was carried out using modulated differential scanning calorimetry (MDSC), dynamic mechanical analysis (DMA), and Raman spectroscopy. Detection of amorphous content in pharmaceutical powders by DMA is a special application of dynamic mechanical spectroscopy. DMA was found to be a sensitive technique, able to detect the presence of an amorphous phase in a crystalline phase at concentrations as low as 0.5%. The limit of detection (LOD) determined for DMA was 2.5%. In comparison, Raman spectroscopy and MDSC had LOD values of 2% and 5% amorphous, respectively.

Drug solubility in fatty acids as a formulation design approach for lipid-based formulations: a technical note

Abstract Lipid-based drug delivery systems have been intensively investigated as a means of delivering poorly water-soluble drugs. Upon ingestion, the lipases in the gastrointestinal tract digest lipid ingredients, mainly triglycerides, within the formulation into monoglycerides and fatty acids. While numerous studies have addressed the solubility of drugs in triglycerides, comparatively few publications have addressed the solubility of drugs in fatty acids, which are the end product of digestion and responsible for the solubility of drug within mixed micelles. The objective of this investigation was to explore the solubility of a poorly water-soluble drug in fatty acids and raise the awareness of the importance of drug solubility in fatty acids. The model API (active pharmaceutical ingredient), a weak acid, is considered a BCS II compound with an aqueous solubility of 0.02 μg/mL and predicted partition coefficient >7. The solubility of API ranged from 120 mg/mL to over 1 g/mL in fatty acids with chain lengths across the range C18 to C6. Hydrogen bonding was found to be the main driver of the solubilization of API in fatty acids. The solubility of API was significantly reduced by water uptake in caprylic acid but not in oleic acid. This report demonstrates that solubility data generated in fatty acids can provide an indication of the solubility of the drug after lipid digestion. This report also highlights the importance of measuring the solubility of drugs in fatty acids in the course of lipid formulation development.