Precision system "prints" individualized med dosages for patients

A mathematical model to predict-and a portable inkjet technology to produce-exact medication dosages tailored for specific patients, an advance in personalized medicine that could improve drug effectiveness and reduce adverse reactions, has been created by Purdue University researchers.

The drug-on-demand system is a precision system that dispenses medication in fluid form onto an edible substrate, to make solid dosage forms. Now, drug manufacturers make tablets based on clinical studies that determine the average recommended dose. If this average falls outside of the optimal dose for a particular patient, there is no way to precisely adjust the dosage except by trial and error. 

“We have demonstrated this with solutions and melts, and plan to demonstrate it with suspensions later this year,” said Arun Giridhar, an associate research scientist in the School of Chemical Engineering, Purdue University.

In the case of solutions, the solvent evaporates after deposition, leaving a solid dosage form behind. In the case of melts, the melt solidifies onto the substrate leaving a solid dosage form as well.

The components of the system are a precision pump to dispense the fluid, a vision system that takes images of fluid drops in mid-air as they are dispensed and calculates their volume to keep track of dosage amounts, an integrated fluid-heating system, appropriate automation and control systems and an edible substrate that is moved in a specified grid pattern beneath the nozzle. Example substrates could be a placebo tablet or an instant dissolve film onto which the drop or drops are deposited.

Many solid dosage forms are made by the blending, processing, and compaction of powders, which are difficult to handle compared to fluids, and pose technical challenges in online measurement and guaranteed consistency, according to Reklaitis.

“Particularly for high-potency medication like oncology agents, where the active ingredient in the tablet may only consist of a less than 20 mg, dealing with fluids provides much better precision and dosage amount control,” said Gintaras “Rex” Reklaitis, Purdue University's Burton and Kathryn Gedge Distinguished Professor of Chemical Engineering.

In addition, this system enables delivery to the patient of an individualized dosage tailored to the patient’s response to the drug.

“The number of different dosage forms made by pharma companies is limited: for example, a given drug may be made in 2 or 3 different dosage amounts, such as 50 mg and 200 mg,” Reklaitis said. “However the optimum dose for a patient may be none of these; this is especially true for chemotherapy agents, for pediatric doses, for geriatric doses, and for cases where the individual patient exhibits atypical drug absorption or drug metabolism. Indeed a significant fraction of drugs in use exhibit high interpatient variability in response.”

Current medical practice is based on starting with the standard dosage recommended by the pharmaceutical company and then sequentially adjusting that dosage based on successive physician-patient interactions until satisfactory balance between therapeutic benefit and side effects is achieved.

“Under the computer-based approach we have proposed and demonstrated using literature clinical data on several drugs, we use patient population data to develop a pharmacometric model of population response to the drug coupled with data from a few blood draws from the specific patient after being treated with that drug, to determine the individualized response of that patient to the drug,” said Poching DeLaurentis, a research scientist in Purdue's Oncological Sciences Center. “This individualized response model is then used to determine the dosage that has the highest probability of delivering the desired therapeutic benefit. The role of the precision drug-on-demand printing system then is to produce this individualized dosage, tailored to the specific patient needs.”

With such a precision manufacturing system, hospitals and pharmacies can print their own drug products in customized dosage amounts and they can use the system in-house, according to Reklaitis. “In the case of solutions, the solvent evaporates after deposition. Operationally, the number of different stock-keeping units to be kept in inventory is considerably reduced. Instead of having multiple dosage amounts of the same drug on hand, the hospital or pharmacy only needs to keep the drug product precursor in bulk containers, which can then be dosed in customized amounts.”

Most important from a clinical point of view, the proposed approach will reduce the number of adverse drug response events, which have been reported nationally to lead to up to 2 million hospital admissions per year and which cumulatively impose a very large cost on the healthcare system.

As individualized medicine is implemented on the compounding pharmacist model, FDA approval is not needed for the printing system. “FDA approval is needed for the specific pharmaceutical agents that will be dispensed with the system, as is current policy anyway,” Reklaitis said. “At this point we have demonstrated feasibility of both the predictive methodology and the drug printing device and reported this in peer reviewed publications. We are currently collaborating with several leading clinics in launching clinical trials in which this overall approach is tested on patients in proscriptive fashion. Moreover, we are currently seeking partners to commercialize the drug printing system itself.”

The system was developed in collaboration with a multidisciplinary team of researchers from the Engineering Research Center for Structured Organic Particulate Systems, involving 4 universities, and a consortium of companies with support from the National Science Foundation. There has been extensive collaboration with GlaxoSmithKline.