In vitro and in vivo testing methods for respiratory drug delivery.

IMPORTANCE OF THE FIELD: Successful respiratory drug delivery for local and systemic purposes is predicated on the availability of in vitro and in vivo methods for determining drug delivery and disposition following respiratory administration. AREAS COVERED IN THIS REVIEW: In this review, the relevance of new in vitro and in vivo methods for screening respiratory drug delivery is discussed. Specific topics covered include in vitro particle size characterization, in vitro dissolution test methods for respiratory formulations and in vitro respiratory absorption and disposition screening methods. Furthermore, in vivo respiratory dosing methods, in vivo respiratory aerosol deposition and drug absorption screening methods, and correlation between in vitro and in vivo methods are reviewed. WHAT THE READER WILL GAIN: After reading this article, the reader will have an enriched knowledge regarding the various in vitro and in vivo testing methods for respiratory drug delivery. Most importantly, this paper will make it possible for readers to appreciate the strengths and weaknesses of each test method, which in turn will assist them in selecting specific methods that suit their scientific needs. TAKE HOME MESSAGE: New in vitro and in vivo methods for screening respiratory drug delivery are indispensible, especially from the respiratory drug development and quality control perspective. Each method has unique advantages and disadvantages that influence method selection and data interpretation. Although in vitro methods are used during drug development, they augment rather than substitute in vivo methods.

Application of process analytical technology in tablet process development using NIR spectroscopy: blend uniformity, content uniformity and coating thickness measurements.

Near-infrared (NIR) spectroscopy was employed as a process analytical technique in three steps of tabletting process: to monitor the blend homogeneity, evaluate the content uniformity of tablets and determine the tablets coating thickness. A diode-array spectrometer mounted on a lab blender (SP15 NIR lab blender) was used to monitor blend uniformity using a calibration-free model with drug concentration ranging from 2.98 to 9.25% (w/w). The method developed accurately depicted the changes in concentration of the drug during blending and the positive effect of a delumping step in the production process. Blend homogeneity was reached within 2 min of the blending step post-delumping, with relative standard deviation (R.S.D.) values varying from 1.0 to 2.5% depending on the drug concentration of the blend. A Fourier-transform spectrometer (Bruker MPA) was used to analyze content uniformity and coating thickness with calibration based models. Prediction of a validation set with tablets compacted at pressures not present in the calibration set yielded an root mean square error of cross validation (RMSEP) of 1.94%; prediction of tablets compacted at pressures present in the calibration set yielded a RMSEP of 1.48%. Performance of the model was influenced by several physical tablet properties, which could be reduced by spectral pre-processing. A model based on reflectance spectra predicted coating thickness and its variation more accurately than the model based on transmission spectra. Inter-tablet coating variation was predicted with NIR and compared to reference thickness measurements. Both methods gave comparable results. Initial inter-tablet variation of tablets sampled in-process during coating was high, but stabilized after 30 min into the process.

Nasal mucoadhesive drug delivery: background, applications, trends and future perspectives.

Nasal drug delivery has now been recognized as a very promising route for delivery of therapeutic compounds including biopharmaceuticals. It has been demonstrated that low absorption of drugs can be countered by using absorption enhancers or increasing the drug residence time in the nasal cavity, and that some mucoadhesive polymers can serve both functions. This article reviews the background of nasal mucoadhesive drug delivery with special references to the biological and pharmaceutical considerations for nasal mucoadhesive drug administration. Applications of nasal mucoadhesives for the delivery of small organic molecules, antibiotics, proteins, vaccines and DNA are also discussed. Furthermore, new classes of functionalized mucoadhesive polymers, the characterization and safety aspects of nasal drug products as well as the opportunities presented by nasal drug delivery are extensively discussed.