Thomas H. Kalantar

Properties and Applications of Microemulsions

Microemulsions are thermodynamically stable, fluid, optically clear dispersions of two immiscible liquids. Recent interest in microemulsion systems has resulted from their utility in a broad range of applications including enhanced oil recovery, consumer and pharmaceutical formulations, nanoparticle synthesis, and chemical reaction media. However, the high levels typically required to ensure complete microemulsification and formulation stability often result in unacceptably high residue, contaminant levels, and formulation cost. One way to reduce surfactant requirements in microemulsion systems is through the use of efficient surfactants and interfacially active cosurfactants. We have explored and developed microemulsion systems based on efficient anionic surfactants and glycol ether cosurfactants that are stable to temperature and compositional changes and yet employ low levels of non-volatile surfactants. These microemulsion systems are finding utility in a range of applications, including consumer and industrial cleaning formulations, chemical reaction media, polymerization, and active ingredient delivery.

A green synthesis of bis[1-(hydroxy-κO)-2(1H)-pyridinethionato-κS2]-(T-4)-zinc (zinc pyrithione) nanoparticles via mechanochemical milling

Particulate bis[1-(hydroxy-κO)-2(1H)-pyridinethionato-κS2]-(T-4)-zinc (zinc pyrithione; ZPT) in the diameter range 0.5–0.7 µm is a US FDA-approved anti-dandruff active widely used in anti-dandruff shampoos. A nanoparticulate form of ZPT is expected to exhibit a higher activity, be distributed more effectively on the scalp, require less thickening agent in the shampoo formulation to ensure its stability against settling than the standard form of ZPT, and would enable clear anti-dandruff shampoo formulations. We demonstrate, for the first time, that a green, mechanochemical nanoparticle synthesis process can be used to prepare nanoparticulate ZPT from zinc chloride and sodium pyrithione monohydrate. Both a Reeves attrition mill and a Retsch MixerMill were found to be effective tools for delivering the mechanical energy needed for the conversion. The infrared spectra and X-ray powder diffraction patterns for the products correspond to those for the known desired material. Transmission electron microscopic analysis indicates that ZPT nanoparticles with primary particle diameters in the range of 20–200 nm (mean diameters of 65–100 nm) can be obtained via this method.

High-Throughput Raman Spectroscopy Screening of Excipients for the Stabilization of Amorphous Drugs.

Low aqueous solubility of active pharmaceutical ingredients (APIs) is an enduring problem in pharmaceutical development, and it is becoming increasingly prevalent among new drug candidates. It is estimated that about 40% of drugs in the development pipeline and approximately 60% of the drugs coming directly from discovery suffer from poor aqueous solubility and slow dissolution, thereby reducing their bioavailability and efficacy and thus preventing their commercialization. It is well known that utilizing the amorphous form of a drug can be a useful approach to improve the dissolution rate and solubility of poorly water-soluble APIs. Amorphous compounds are thermodynamically unstable, but they can be stabilized by combining them with a carrier polymer (excipient) to form a solid dispersion. High-throughput Raman spectroscopy was used in this study to identify excipients that promote formation and stabilization of the amorphous drug form in solid dispersions. Four model APIs were used as poorly soluble drug candidates: ketoprofen, danazol, griseofulvin, and probucol. The Raman signals of excipients were generally negligible, and therefore Raman bands from the drugs were used with minimal spectral pre-processing. By comparing Raman spectra collected from the APIs in the crystalline and molten state, appropriate spectral features and regions were identified for the development of semi-quantitative methods to determine the amorphous content for each API. It is demonstrated that methods based on peak intensity ratio, peak width, peak distance, and classical least squares can all be effective methods for the screening of excipients. Interesting excipient-dependent phase transformation behavior was also observed for probucol.