Drug release formulation factors

A reported application of canonical analysis involved a novel combination of the canonical form of the regression equation with a computer-aided grid search technique to optimize controlled drug release from a pellet system prepared by extrusion and spheronization [28,29]. Formulation factors were used as independent variables, and in vitro dissolution was the main response, or dependent variable. Both a minimum and a maximum drug release rate was predicted and verified by preparation and testing of the predicted formulations. Excellent agreement between the predicted values and the actual values was evident for the four-component pellet system in this study. 

C. B. Lalor, G. L. Flynn, and N. Weiner. Formulation factors affecting release of drug from topical formulations. I. Effect of emulsion type upon in vitro delivery of ethyl p-aminobenzoate. J. Pharm. Sci. 83 1525-1528 (1994). 

The effects of various formulation factors on the in vitro release characteristics of spherical polymethylmethacrylate implants were studied. Physical and mathematical models were proposed to describe the in vitro release profiles. The in vitro release data could be described by a biexponential equation of the following type fraction of tobramycin remaining in the implant at time t=Aerai+BQ, where a, and P represent the rate constants for the initial rapid and subsequent slow phases of release. The influence of drug loading, volume of dissolution medium, implant size and type of cement and the incorporation of water-soluble additives on the release profiles and a and P rate constants is described. 

Kader A, Jalil R. Formulation factors affecting drug release from poly(lactic acid)(PLA) microcapsule tablets. Drug Dev Ind Phann 1999 25(2) 141 151. 

The degree of ionization under physiologic conditions Product formulation characteristics Disintegration and dissolution rates for solid dosages Drug release characteristics for timed-release preparations Patient factors... 

The calculation of the factors from the mean profiles of the two drug products presupposes that the variability at each sample time point is low. Thus, for immediate release formulations, the FDA guidance [137] allows a coefficient of variation of no more than 20% for the early data points (e.g., 10 or 15min), while a coefficient of variation less than 10% is required for the other time points. 

Safety is a prime concern in the development of pharmaceutical products. A drug that has an excellent therapeutic effect cannot be released to the market if it has serious adverse effects. Extensive pharmacologic studies and strict evaluations of CAs are required before gaining approval from the Food and Drug Administration (FDA). Factors assessed include the formulation, hemodynamic effect, toxicity, adverse effects, viscosity, osmolality, and immunogenicity of the agent [86]. 

Aside from the physicochemical properties of the polymer itself, there are additional factors that can influence drug release and the performance characteristics of the dosage form. Examples of these factors are highlighted in Table 3. Dosage forms can be formulated into a wide range of geometries and physical... 

It is not the aim of this article to evaluate formulation aspects that may influence dissolution of drugs from dosage forms. However, it suffices to mention that dissolution rates of drug substances or drug release from formulated products may be influenced (increased or decreased) by factors such as assay selection, the presence of surfactants, polymorphic modification, and by the use of water-soluble carriers in solid dispersions. 

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