Critical Points in Inert Matrices

There are many factors that affect the drug release from inert matrices such as concentration and solubihty of the drug, type of polymer, utilization of polymer blends, particle size of the drug and polymer and hydrophobia of the other excipients that can be employed (fillers, lubricants, binders, etc.). 

Besides what has been previously explained, it is advisable not to formulate the system in the closeness of the percolation threshold of its components, since they are areas of great variability that will result in unpredictability in the biopharmaceutical and mechanical behavior. Therefore, the knowledge of the critical points of drugs and polymers, and the influence of the different factors that affect these critical points, lead to more robust formulations and an important decrease in the costs of the optimization process and the time to market [83]. 

The p property was proposed by Bonny and Leuenberger, knowing that the universal exponent for conductivity and transport properties is p = 2.0 in three dimensions, and arranging the release parameters in order to have a property that depends linearly on the drug percolation threshold. 

according to the fundamental equation of the percolation theory (Equation 4.2), it can be assumed that  

The drug percolation threshold or including the drug content and the initial pores for these matrices, ranged between 30-36% (w/w). With respect to the excipient percolation threshold, p, differences were found between EC (critical point aroimd 30% w/w) and HCO matrices (6% w/w). The very low percolation threshold of the lipidic matrix-forming excipient was attributed to the different particle sizes of matrixforming excipient and active substance, being the HCO particle size much smaller than the caffeine particle size. The effect of the particle size of a substance in its percolation threshold will be discussed later. 

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