Parameters Influencing Drug Release

The initial stage of drug release from the formulation, both in terms of the amount and the rate of release, may exercise considerable influence at the clinical response level. A close consideration of the formulation parameters of any chemical is therefore essential during the development of any new drug, and, indeed, there are examples where formulations of established drugs also appear to require additional investigation. 

Initial process development A preliminary study was established to examine the potential influence of processing parameters on some critical performance attributes of the final product, especially those associated with ultimate drug release rate, and the reproducibility of same. 

In hydrophilic matrices the drug threshold is less evident than the excipient threshold, which is responsible for the release control [73], In order to estimate the percolation threshold of HPMC K4M, different kinetic parameters were studied Higuchi rate constant, normalized Higuchi rate constant, and relaxation rate constant. The evolution of these release parameters has been studied as a function of the sum of the excipient volumetric percentage plus initial porosity. Recent studies of our research group have found the existence of a sample-spanning cluster of excipient plus pores in the hydrophilic matrix before the matrix is placed in contact with the liquid, clearly influences the release kinetics of the drug [73]. 

The thermal properties of polymers are important parameters to consider as they play key roles in the mechanical properties of biomaterials used in bone repair and prosthesis materials. These properties may also influence the drug-release properties of drug-delivery devices. Information is provided about the mobility of the polymer chains within a material at a given temperature and about the crystallinity of this material (see also Section 2.4). This characterisation is also useful in order to determine whether a polymer material is a hard or soft solid or a liquid at a given temperature. 

Drug delivery systems have been developed for doxorubicin [51] (a drug used to treat leukemia but which has cardiac risk factors), and for flavors such as decanoic acid [52]. In both cases, the encapsulation efficiency as given by load, recovery speed and recovered quantity was assessed. In addition, the stabihty (shelf life) of such gel matrices in terms of stabihty of the pharmaceutically active ingredient was increased compared to their free form. Similar appHcations for coatings for the controlled release of biocides [53] and other pharmaceuticals such as vitamins [54] have also been made. Clearly, gel porosity, pore size distribution, temperature, pH all influence the release, and these parameters must be optimized. 

Inlereslingly, ihis equation defines the parameters that will influence the subsequent delivery of therapeutic agents and is consequently used to engineer drug release. For a more comprehensive mathematical description of drug release from reservoir systems the reader is invited to consult the excellent text by Chien (a.47). 

---