Are Mathematical Equations Important for Improving Drug-Delivery Devices Performances?

Drug delivery & mathematical modelingMathematical theories applied to drug delivery represent an extremely interesting field of increasing academic and industrial importance with tremendous consequences for the future due to the possibility of predicting and tuning the release of drugs 1,2.Thanks to significant advances in computer science and electronics, the optimization of drug delivery systems using computational approaches can be expected to successfully improve the ease and accuracy of application 3,4.Similar to what is happening in other disciplines that seem far removed from the drug delivery field, such as aviation or reactive systems, computational efforts are becoming fundamental to research into future improvements in pharmaceutical technology 5,6.Taking into consideration the type of administration, the active principle of the cargo and the desired release kinetics, the predictions obtained from in silico studies can be used to estimate the optimized formulation, shape and manufacturing procedure of the dosage form to be produced.In this respect, mathematical models used in the optimization of drug delivery devices can help to save time and reduce expenses 7,8.In fact, predictions obtained from theoretical studies can reduce the number of experiments needed to develop or optimize drug delivery devices.Furthermore, the correct knowledge of all the phenomena (mass and energy) that can take place in controlled drug delivery systems can be another key point in convincing the audience of the importance of this study.In particular, it could help to improve the safety and efficacy of new pharmaceutical therapies, which is a prerequisite for their development, underlining once again the importance not only from an academic but also from an industrial perspective 9.It is indeed true that knowing what is happening in a system, instead of considering it as a 'black box', is fundamental in the whole decision-making process, starting from the laboratory formulation and procedures through good manufacturing practice (GMP) production to clinical trials and commercialization.This approach is fundamental in determining which device characteristics are critical to achieving the system performance required by medicine.In the last decades, many different models have been developed and are available in the literature 101112, but most of them are still lacking in ease and accuracy of operation.The pioneer of theories applied to the transport of drug molecules through polymeric devices is Professor Higuchi (1918-1987), followed more recently by Professors Peppas and Siepmann 10.In 1961, Professor Higuchi published his famous equation, which allowed an unexpectedly simple description of drug release using semi-empirical parameters depending on the geometry studied 13,14.This was the beginning of understanding how drugs could be released from pharmaceutical forms.To date, many different models have been described, including semi-empirical/empirical models and mechanistic realistic models.In the first case, the mathematics is purely descriptive and not strictly related to real natural, physical and/or chemical phenomena.As a result, these models provide only very limited insight into the mechanisms of delivery through the devices, and their predictive ability is very low.However, they can be useful if the information