[top]Introduction to Insufflation / Intranasal administration
Intranasal (IN) administration of drugs
and medications is dependent on many drug
factors but provides a convenient alternative to oral and intravenous (IV) or intramuslcular (IM) routes. When a drug is administered orally it is absorbed and enters the hepatic portal vein and goes to the liver before entering circulation within the rest of the body. This makes it subject to first-pass metabolism by the liver and this greatly reduces the bioavailability (how much of the drug enters circulation) of the drug. IV and IM administration of a drug avoids this problem entirely but it is very invasive for the subject and also more impractical for long term or daily use of a drug. IN administration offers several advantages in comparison to these two other routes of administration (ROA), including the potential to bypass the blood brain barrier altogether, and directly administer a drug to the brain and central nervous system. 
There are many factors that affect the delivery of a drug to blood circulation and the central nervous system. The nasal passageways are highly vasularized which aids in the absorption of drug via IN administration, but drug factors such as solubility, stability, molecular weight, and hydrophobicity affect absorption. 
[top]How Insufflation works
When a drug in insufflated the material makes contact with the epithelial cells of the nasal membranes when it dissolves or mixes in the mucous. A drug can then be absorbed by one of two pathways, transcellular transport and paracellular transport. A drug that enters the body transcellularly passes into and through the cells that make up the membrane, and paracellular transport refers to a drug which enters the body between cells, in the paracellular space, where tight junctions hold the cells together and prevent some molecules from passing into the tissue. On a side note, typical capillaries contain gaps that allow for the free flow of substances out and into the blood, while capillaries in the brain contain tight junctions to prohibit many drugs and other substances from leaking into the tissue and surrounding neural cells.
Hydrophobic molecules of a low molecular weight tend to enter the tissue via the transcellular pathway, while hydrophilic molecules generally enter via the paracellular pathway, and the latter is also possible when a drug is prepared in such a way that the tight junctions are opened. For the majority of recreational substances, lipophilicity is the most important factor determining their absorption. Larger molecules such as peptides may interact with glycoprotein chains in the mucus and this could pose a barrier. Fat soluble compounds can permeate the cell bilayer and right into the cell in the nasal membrane. It was also determined that low molecular weight compounds like para-aminohippuric acid also passed into the tissue quite easily as well. 
1. Pharmacokinetic Attributes of Intranasal Delivery: Case studies and new opportunities. (2005). ONdrugDelivery Ltd. www.ondrugdelivery.com
2. SHYEILLA V. DHURIA, LEAH R. HANSON, WILLIAM H. FREY II. (2009). Intranasal Delivery to the Central Nervous System: Mechanisms and Experimental Considerations. Published online 29 October 2009 in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002
3. Priyanka Arora, Shringi Sharma and Sanjay Garg. (Nov. 18 2002). Permeability issues in nasal drug delivery. Elsevier Science Ltd.
4. Intranasal delivery: Physicochemical and therapeutic aspects. (2007). Henry R. Costantino, Lisbeth Illum, Gordon Brandt, Paul H. Johnson, Steven C. Quaya. International Journal of Pharmaceutics 337 (2007) 1–24.