Good Practices for the Laboratory Performance Testing of Aqueous Oral Inhaled Products (OIPs): an Assessment from the International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS).

Multiple sources must be consulted to determine the most appropriate procedures for the laboratory-based performance evaluation of aqueous oral inhaled products (OIPs) for the primary measures, dose uniformity/delivery, and aerodynamic particle (droplet) size distribution (APSD). These sources have been developed at different times, mainly in Europe and North America, during the past 25 years by diverse organizations, including pharmacopeial chapter/monograph development committees, regulatory agencies, and national and international standards bodies. As a result, there is a lack of consistency across all the recommendations, with the potential to cause confusion to those developing performance test methods. We have reviewed key methodological aspects of source guidance documents identified by a survey of the pertinent literature and evaluated the underlying evidence supporting their recommendations for the evaluation of these performance measures. We have also subsequently developed a consistent series of solutions to guide those faced with the various associated challenges when developing OIP performance testing methods for oral aqueous inhaled products.

The state of nano-sized titanium dioxide (TiO2) may affect sunscreen performance.

In the past several years, there has been a trend in the sunscreen/cosmetics industry to replace micron-sized titanium dioxide (TiO(2)) particles with nanoscale materials. The increased use of nanoscale TiO(2) has resulted in questions about these and other nanoproducts. This study examines the effects of using nanoscale TiO(2) on ultraviolet (UV) attenuation in simple to complex sunscreen formulations. UV light attenuation, product stability, and potential damage to the skin barrier were examined with both nanoscale and microscale TiO(2) particles. Results indicate that none of the formulations decreased the barrier function of the skin and the best UV attenuation occurs when the TiO(2) particles are stabilized with a coating and evenly distributed such as with non-agglomerated coated nanoscale materials. This indicates that nanoscale TiO(2) may have better efficacy while lacking toxicity.

Supplemental dietary carnitine and lipid metabolism in exercising rats.

Rats were physically trained by treadmill running and fed normal, high fat, or identical diets supplemented with 1.0% D,L-carnitine. Fatty acid oxidation, stimulated by exercise and/or by a high fat diet was studied to determine if it might be further augmented by supplemental dietary carnitine. Fatty acid oxidation in vitro or in vivo was unaffected by carnitine feeding. Carnitine feeding was associated with an increase in heart and muscle palmitylcarnitine acyltransferase activity and reduced serum cholesterol in trained rats fed the high fat diet. Under the conditions of this study, supplemental dietary carnitine did not greatly alter glyceride synthesis, lipolysis, or fatty acid oxidation, which indirectly indicates that the increased demands for fatty acid oxidation resulting from exercise or from fat feeding are adequately supported by endogenous levels of carnitine.

Gradient liquid chromatographic method for determination of chlorhexidine and its degradation products in bulk material.

A liquid chromatographic method was developed for determination of chlorhexidine and its degradation products in unformulated drug substance. A nonlinear gradient from 80% 0.1M ammonium acetate buffer, pH 5.0, to 20% buffer over 90 min (balance is acetonitrile) is applied to a 3 microns octadecylsilane bonded-phase column. The drug and some of its degradation products are determined at 230 nm. Of 11 previously identified degradation products, 9 are determined with good precision (relative standard deviation of peak area is < 2%).

Identification and isolation of chlorhexidine digluconate impurities.

We report the identification of 11 impurities in variously stressed chlorhexidine digluconate (CHG) solutions. The structural assignment of each CHG impurity involved tentative identification from HPLC-MS data followed by synthesis of the appropriate standard, isolation of the impurity from the CHG solution by flash chromatography, and comparison of HPLC-MS, HPLC-UV, and NMR data of the impurity with the standard. Six of the synthetic impurity standards represent new compounds. Degradation studies of CHG solutions systematically stressed by heat, light, and low pH are reported with identification and approximate quantification of resulting impurities. Degradation mechanisms were proposed for each set of stress conditions applied to CHG solutions. Parallels were noted between the way CHG degrades in the thermospray interface of the HPLC-MS and the way CHG degrades with shelf time. Similarities were noted in the synthetic starting materials of CHG and the final degradation products.

Lipogenesis and glyceride synthesis in the rat: response to diet and exercise.

The responses of hepatic and adipose tissue malic enzyme (ME), citrate cleavage enzyme (CCE), glucose-6-phosphate dehydrogenase (G6PD), and glyceride synthetase (GS) to exercise training and exhaustive exercies and the potential of a high fat or high carbohydrate diet to modify these responses were studied in male Carworth rats. Characteristic elevation and depression of ME, CCE, and G6PD were decreased in skeletal muscle, liver, and adipose tissues of high carbohydrate-fed rats. A significant two-way diet-training interaction was indicated for hepatic ME and G6PD. This interaction resulted from an apparent training modulation of ME and C6PD responses to the high fat and high carbohydrate diets. Adipose tissue G6PD was significantly decreased by training. Exhaustive exercise performed immediately prior to sacrifice did not significantly alter ME or CCE activities in either liver or adipose tissues, but decreased adipose tissue G6PD in untrained rats. Exhaustion was also associated with decreased GS activity in muscle and liver. Physical training was associated with a significant increase in GS in muscle and adipose tissues. In contrast to glyceride synthesis, no increase in adipose tissue lipogenic potential was noted in response to training, indicating that the physically trianed rat may have an enhanced ability to store but not synthesize fatty acids.