Drugs Delivery Rate

The acid-base chemistry of nicotine is now well known and investigations have shown that nicotine in tobacco smoke or in smokeless tobacco prodncts can exist in pH-dependent protonated or nnprotonated free-base forms. In tobacco smoke, only the free-base form can volatilize readily from the smoke particnlate matter to the gas phase, with rapid deposition in the respiratory tract. Using volatility-based analytical measurements, the fraction of nicotine present as the free-base form can be quantitatively determined. For smokeless tobacco products, the situation differs because the tobacco is placed directly in the oral cavity. Hence, the pH of smokeless tobacco prodncts can be measured directly to yield information on the fraction of nicotine available in the nnprotonated free-base form. It is important to characterize the fraction of total nicotine in its conjugate acid-base states as this dramatically affects nicotine bioavailability, because the protonated form is hydrophilic while the nnprotonated free-base form is lipophilic and thus readily diffuses across membranes (Armitage and Turner 1970 Schievelbein et al. 1973). As drug delivery rate and addiction potential are linked (Henningfield and Keenan 1993), increases in delivery rate due to increased free-base levels affect the addiction potential. 

Key parameters that can be used to modulate the drug delivery rate or spatial targeting... 

Blending is yet another way of manipulating the polymer properties. PTMC degrades too slowly to be useful for most drug delivery applications. Blends were prepared in an attempt to enhance and control the drug delivery rate [121]. Films were prepared from PTMC and poly(adipic anhydride) (PAA), which were partially miscible and formed macroscopically homogeneous blends. The PAA was found to act as a plasticizer and facilitated the erosion of PTMC by increasing the porosity and hydration. PTMC-PAA blends offered sustained and controllable release of an incorporated therapeutic substance as shown in Fig. 11 [121]. 

Where is the area of the patch Qp, the concentration of drug in the patch R, the overall resistance and R, the resistance to release from the patch. There are a number of situations one can consider, such as the patch resistance limits the delivery, diffusion through the epidermis limits delivery, or the concentration of the drag is kept constant in the patch by using solid hydrogels. When diffusion through the epidermis layer limits, the rate of drug delivery rate is... 

However, this particular polymer has a very low glass transition temperature and when thin disks are placed in an aqueous environment, they undergo deformation and the consequent irreproducible change in surface area results in changes in drug delivery rates. For this reason, work with the linear polymer has been discontinued and work is currently in progress using crosslinked polymers which maintain their shape. This work has already been described in Sect. 4.2.4, Control of polymer hydrophilicity. 

This is 7.5 times Jtjor the polymer coating, so external diffusion controls, and the drug delivery rate can be estimated from a first-order equation. 

It is safe to assume that for a given dissolution device, the ultimate drug delivery rate will be a combination of hydrolysis (dissolution) and drug diffusion out of the polymer. Of the systems stuped to date, the release rates for biodegradable devices are essentially zero-order. 

Horcajada P, Rdmila A, P6rez-Pariente J, Vallet-Regl M (2004) Influence of pore size of MCM-41 matrices on drug delivery rate. Microporous Mesoporous Mater 68(1-3) 105-109 Hu Y, Zhi Z, Zhao Q, Wu C, Zhao P, Jiang H, Jiang T, Wang S (2012) 3D cubic mesoporous silica microsphere as a carrier for poorly soluble drug carvedilol. Microporous Mesoporous Mater 147 94-101... 

Munoz, B., Ramila, A., Perez-Pariente, J., Diaz, I. and Vallet-Regi, M. (2003) MCM-41 organic modification as drug delivery rate regulator. Chemistry of Materials, 15, 500-3. 

Solution The volume of drug solution per time is just the drug delivery rate divided by the concentration ... 

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