Opportunity and challenges of nasal powders: Drug formulation and delivery

The blood-brain barrier (BBB) limits the distribution of systemically administered therapeutics to the central nervous system (CNS), posing a significant challenge to drug development efforts to treat neurological and psychiatric diseases and disorders. Intranasal delivery is a noninvasive and convenient method that rapidly targets therapeutics to the CNS, bypassing the BBB and minimizing systemic exposure. This review focuses on the current understanding of the mechanisms underlying intranasal delivery to the CNS, with a discussion of pathways from the nasal cavity to the CNS involving the olfactory and trigeminal nerves, the vasculature, the cerebrospinal fluid, and the lymphatic system. In addition to the properties of the therapeutic, deposition of the drug formulation within the nasal passages and composition of the formulation can influence the pathway a therapeutic follows into the CNS after intranasal administration. Experimental factors, such as head position, volume, and method of administration, and formulation parameters, such as pH, osmolarity, or inclusion of permeation enhancers or mucoadhesives, can influence formulation deposition within the nasal passages and pathways followed into the CNS. Significant research will be required to develop and improve current intranasal treatments and careful consideration should be given to the factors discussed in this review. 2009 Wiley-Liss, Inc. and the American Pharmacists Association

There is an obvious need for efficient and safe nasal absorption enhancers for the development of therapeutically efficacious nasal products for small hydrophilic drugs, peptides, proteins, nucleic acids and polysaccharides, which do not easily cross mucosal membranes, including the nasal. Recent years have seen the development of a range of nasal absorption enhancer systems such as CriticalSorb (based on Solutol HS15) (Critical Pharmaceuticals Ltd), Chisys based on chitosan (Archimedes Pharma Ltd) and Intravail based on alkylsaccharides (Aegis Therapeutics Inc.), that is presently being tested in clinical trials for a range of drugs. So far, none of these absorption enhancers have been used in a marketed nasal product. The present review discusses the evaluation of chitosan and chitosan derivatives as nasal absorption enhancers, for a range of drugs and in a range of formulations such as solutions, gels and nanoparticles and finds that chitosan and its derivatives are able to efficiently improve the nasal bioavailability. The revirtew also questions whether chitosan nanoparticles for systemic drug delivery provide any real improvement over simpler chitosan formulations. Furthermore, the review also evaluates the use of chitosan formulations for the improvement of transport of drugs directly from the nasal cavity to the brain, based on its mucoadhesive characteristics and its ability to open tight junctions in the olfactory and respiratory epithelia. It is found that the use of chitosan nanoparticles greatly increases the transport of drugs from nose to brain over and above the effect of simpler chitosan formulations. Copyright © 2014 Elsevier B.V. All rights reserved.

Over 40% of active pharmaceutical ingredients (API) in development pipelines are poorly water-soluble drugs which limit formulation approaches, clinical application and marketability because of their low dissolution and bioavailability. Solid dispersion has been considered one of the major advancements in overcoming these issues with several successfully marketed products. A number of key references that describe state-of-the-art technologies have been collected in this review, which addresses various pharmaceutical strategies and future visions for the solubilization of poorly water-soluble drugs according to the four generations of solid dispersions. This article reviews critical aspects and recent advances in formulation, preparation and characterization of solid dispersions as well as in-depth pharmaceutical solutions to overcome some problems and issues that limit the development and marketability of solid dispersion products.