Intranasal Eutectic Powder of Zolmitriptan with Enhanced Bioavailability in the Rat Brain.

Intranasal administration can potentially deliver drugs to the brain because of the proximity of the delivery site to the olfactory lobe. We prepared triturates of micronized or crystalline zolmitriptan with a GRAS substance, nicotinamide, to form a eutectic. We characterized the formulation using differential scanning calorimetry, powder X-ray diffraction, and FTIR spectroscopy to confirm its eutectic nature and generated a phase diagram. The eutectic formulation was aerosolized using an in-house insufflator into the nares of rats. Groups of rats received zolmitriptan intravenously or intranasally, or intranasal eutectic formulation. Zolmitriptan was estimated in the olfactory lobe, cerebral cortex, cerebellum, and blood plasma at different time-points by LC-MS. Pharmacokinetics in these tissues indicated the superiority of the intranasal eutectic formulation for brain targeting when compared with results of IV solution and intranasal pure zolmitriptan powder. Enhancement of nose-to-brain transport is likely to have resulted from more rapid dissolution of the eutectic as compared to pure drug.

Particulate pulmonary delivery systems containing anti-tuberculosis agents.

There is renewed interest in delivering anti-tuberculosis (TB) drugs to the lungs by inhalation. Several groups have investigated particulate pulmonary drug delivery formulations containing anti-TB agents, prepared using a variety of design approaches and processes. This review summarizes trends that indicate feasibility and translation of research efforts aimed at developing inhaled therapies for TB. Whereas formulations intended for reconstitution as solutions prior to nebulization can be produced with relative ease, particle engineering for powder formulations is more specialized. Spray drying and emulsion methods used to prepare particulate pulmonary delivery systems of anti-TB agents are compared. Pharmaceutical characterization is outlined. Administration of repeated inhalations to laboratory animals, especially under Animal Biosafety Level-3 (ABSL-3) containment as required for TB research, is another major challenge. Techniques employed by different groups are reviewed in the context of suitability for drug delivery and amenability towards use in ABSL-3 settings. It is concluded that spray drying is suitable for production of inhalable particles, rigorous physicochemical characterization is necessary for developing inhaled therapies as drug products, and pulmonary delivery of formulations containing anti-TB drugs to animals infected with Mycobacterium tuberculosis can best be carried out using handheld devices.