In a previous article, we looked at how SLS, SLA, inkjet and FDM are making pills customized. 3D printing pharmaceuticals so that patients get exactly the right dose is a burgeoning research area. We believe that this has a lot of potential, so we’ve done articles on startups who are 3D printing pills such as FabRx, Anelle O and Craft Health. We’ve also editorialized about just how impactful that this could be for healthcare, looked at how people are using desktop 3D printers to print pills, the first approved 3D printed drug, how mouthguards are being used as well as IUD’s, how people are making micro reservoirs and specific doses for kids. We’ve brought you several overview & review papers and more on the subject.
Aside from the obvious, what exactly can one customize on a pill through 3D printing? In the literature, the main focus is on dosage and changing release profiles. By giving a drug a much faster release profile, for example, an old drug could be made more effective or even be used for a new disease. In the future, one could even envision individualized release profiles for each patient or different release profiles throughout one treatment for one individual. Release profiles and doses could also be tailored to different groups of people or depending on the circumstances. In many cases, the expectation is that regulatory approval would be far less costly than with introducing new substances because, after all, we’re not inventing a new pancake batter; we’re just using the existing recipe to make waffles.
Since drug companies are chiefly engaged in unicorn hunting, whereby they are continually looking for new substances for popular long term first world subscription diseases, this opportunity may be of limited interest to them. One central consideration for the drug company is if the material can be patented and protected. Taking a long look through existing portfolios is not a principal activity. Considering the sheer financial benefits, however, it perhaps should be. Drug companies can still mine their existing IP for billions through making their treatments more effective or redirecting them. In some cases, they may be able to seek additional layers of protection for new ways of administring those drugs or of new shapes for those drugs. This is all really new for everyone, so time will tell, but I do believe that there is an extensive opportunity there.
Below I’ve compiled a list of possible adaptations and customizations one could do using 3D printed pills. Partially the list appears in the literature, and the rest I’ve come up with myself. All of the 3D printing methods and below could be used to optimize release kinetics overall, diffusion, targetting, solubility, locality, mixing, wettability, or other characteristics to aid in the overall efficacy of the medication. I just generally mention release here as the desired characteristic, but it may mean other things than just the release profile (I wanted to be efficient). Sometimes I suggest other specific advantages, but these are not intended to be exhaustive.
- Individual dose: we could individualize the dosage itself per patient depending on their condition, weight, test outcomes, or any number of attributes.
- Disease based dose: We can individualize a treatment based on the seriousness of a condition or a disease’s stage.
- Running dose: we could continually on demand produce individualized tablets depending on how a patient responds to treatment.
- Group Dose: we could manufacture group-specific doses for groups such as pregnant women, people over 60, or people with certain counterindications.
- Fortified dose: We could add in new medications along with existing medicine per group or locale depending on the conditions there.
- Release Shape of Shell: We could adapt the tablets shell shape for optimal release.
- Release Texture of Shell: We could change the texture of the tablet’s shell to optimize release characteristics.
- Release Forms: We could apply shapes to the surface or subsurface of a shell to delay, break up, or accelerate release.
- Porosity: We could design for certain porosities in the outer shell (or indeed in subsequent internal shells as well) to optimize release or other characteristics.
- Release Holes: We could print specific holes at specific locations to optimize release, mixing, wettability, or other characteristics.
- Coating: We could 3D print on a coating to change the pills by adding an active coating that has medicinal value or a coating that adds aroma or another nonmedicinal property to a medication.
- Coating Texture: We could adapt the coating to include a texture to aid in the passage through the throat, for example.
- Tunable Coatings: We could make layers of coatings to change the wettability or release profiles or indeed have many releases inside one pill (outer layer disintegrates, inner works 24h, core a week).
- Pill in a Pill: We could have different medications to be taken serially, each stacked inside each successive layer of a tablet.
- Different Medications: We could generally have different medications inside a pill.
- Event-Driven Medications: If the Ph of the stomach acid is above 3, the shell dissolves.
- Event-Driven Pill in Pill: Medication is released, small pills inside the dose stay intact unless Ph is above 3.
- Layer Thickness of Pill Shell: We can easily change the layer thickness and overall wall thickness of the tablet.
- Surface channels: We could 3D print channels on the surface that would, for example, change wettability.
- Gaplets: gaplets in the surface could help the pill disintegrate faster.
- Air: We could let in, encapsulate air or make the pill float rather than sink.
- Flexibility: Tablets could be designed to be more flexible to aid in passage.
- Wall Thickness Internal: We can change the thickness of the printed dose layers to change absorption or other characteristics.
- Textures dose: We can apply textures to the dose itself to change absorption, wettability, etc.
- Coating dose: The dose inside the pill can have several coatings.
- Effective coatings: These successive coatings could be 3D printed of other medicines or active compounds each optimized to have effects at the right event or point in time.
- Shapes of the dose: the dose itself can be shaped for optimization.
- Dose Forms: We could 3D print small shapes on the surface of the dose or internally to it to alter the efficacy of the medicine.
- Dose channels: We could 3D print channels on the surface of the dose or inside of it.
- Infill percentage: We could have a higher or lower infill to accelerate release.
- Infill shape 2D: We could alter the raster of 2D shapes that the infill is made in to change the release profile.
- Chessboard Infill: We could fill some infill structures but skip a defined number of others in effect, creating air gaps inside of the pill.
- Compartlets: Compartmentalized pills with perhaps many compounds in them all in a series of smaller compartments.
- Disintegrating compartments: Similar to Spitam we could have the inside or the outside disintegrate quickly once the outer layer is breached, but they are different than gaplets or the disintegrating surface because these compartments can contain active compounds.
- Infill shape 3D: We could change the 3D shape of infill.
- Internal structures: Internal structures of the dose itself could also be individualized for disintegration and other desirable characteristics.
- Bonding optimized: We could make micro or nanosized parts that are optimized for bonding to in or with parts of the body.
- Variable release profiles in one pill: We could have an initial zero-order release profile that becomes a pulsatile release profile later on.
- Pressure-sensitive release: In case of pressure being above a certain point, structures internally could be designed to crumble.
- Targetted dose: Doses could be optimized for a precise location.
- Mixed dose: A dose could contain two diverse, active compounds in the pill itself that would act in conjunction but as sperate entities in the body. These could have different release profiles.
- Polypill: A pill could contain two separate but simultaneously released compounds.
- Separated dose: A dose could contain two incompatible compounds and release them when ready.
- Two-Component Dose: A dose could contain two separate compounds that, when appropriately combined, form either a third or some combination of the two compounds.
- New Codrugs: New types of codrugs may be developed that can be combined whereas they previously were not able to be.
- Multipill Side: for certain groups of at-risk people, multiple medications in one pill could be included as standard eg, deworming or iodine in areas where this is a problem (differs from Fortified dose in that in this case there are several pills inside the main pill. This could be done because of compatibility issues for example.
- Multipill Disease: Similar to multivitamins, more multiple treatments could be devised eg, one zinc, antibiotic and ORS pill for cholera.
- Condition-specific response: A medicated stent that if the pressure drops in the artery, it then releases blood thinners (different from event based in the sense that with event-based it is a pill lying in wait for a certain event to occur once. With condition-specific it could be a long term pill that could manage a condition by only responding when appropriate).
- Medicated stents: coatings 3D printed on stents or other devices.
- 3D printed stents: 3D printing the entire stent or device.
- Micro implants: small long term drug release implants.
- Micro Swimmers: mechanical devices that move through the body or are designed to perform some mechanical action.
- Medicated Instruments: 3D printed active coatings on medical instruments to make them more useful.
- Microneedles: that precisely target drugs.
- 3D printed disposables: disposables that are printed and/or have medical compounds printed on them to make them more useful.
- Dual-use Disposables: an IV needle with a fentanyl test material printed on top of it so that the needle changes color if the drug is detected also precluded the additional action of placing a strip.
- Not So Disposables: An IV needle that once used is sent to the lab for testing so no separate injection is required.
- 3D Printed Patches: drug, drug release patches with a specific shape to make them more effective or coated in a drug through 3D printing. Eg, a patch could be made so that it fits inside the nose comfortably.
- Holdfast devices: A medicated polymer 3D print could be made in any number of shapes to fulfill a function eg, holding in the IV but also simultaneously release a drug.
- Customized Drug Delivery Parts: Manufacturing individualized better fitting mouthguards, noseguards, ear implants that deliver drugs locally. Eg, medicated Invisalign.
- Orphan medications: printing small series of tablets for orphan treatments.
- Dialing in the therapeutic window: with some day to day medications, it may prove effective to change the dosage by printing many different ones until the right one is found iteratively by testing it on that one patient.
- Quality assurance: to prevent tampering or to ensure that the pills have always been kept at the right temperature microdots, strips, or circuits could be 3D printed on pills, doses, or containers.
- QR code: Drugs can be QR code shape or contain easily scanned QR codes to let them be identified.
- Comm Pills: Pills or implants could have antenna 3D printed on them to report values back to doctors or users.
- Active Comm Pills: A NFC or other communication could be sent to a microswimmer with 3D printed antenna telling it to release more drugs.
- Edible Tide Pods: Pills could be made to be colorful or attractive so that kids or other groups could accept them more.
- Physical Guides and Warnings: Dangerous pills could be made with sharp edges and in red to warn patients that they should be careful with them. A tablet could be the shape of an apple to remind the user to take it only with food.
- Lettering: individual instructions could be printed on the pill itself (could be 2D also) but for the blind specifically 3D letters and 3D printed braille on pills could be very helpful,
- Print Candy: One large pill’s dose could be 3D printed on an existing Snickers bar to make it easier for kids to eat.
- Container Print: The ORS could be printed inside the cup so that one needs to add water to a fill line to get the right dose.
- Food: medications and nutrients could be 3D printed and added to hospital food, so the patient unobtrusively gets their medication. The structure and individual nutrients of that food could be specific to the patient. With Print Candy you’re printing on an unchanged food, here you’re 3D printing the entire food.
- New Delivery Mechanisms: A topical medication could be 3D printed on a soap bar to make it easier to apply.
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