Phase I: Advancements in oral solid dose
Phase II: Evolution of oral solid dose technology
In the era of advancing technology, a new frontier in health care is emerging to bridge the gap of oral delivery of biologics through the concept of digitized drugs. Insulin is a prime candidate for conversion to OSD.
People with type 1 diabetes must inject insulin every day, often up to 4-5 times per day. However, when insulin is ingested in the form of a traditional tablet, it gets degraded by stomach acids, rendering it ineffective before it can reach the intestines, where it needs to be absorbed into the bloodstream to regulate blood glucose levels.
To overcome this issue, scientists have previously tried to protect insulin from stomach acid by using micro- or nanocarriers. However, these approaches relied on insulin passively diffusing into the cells that line the colon, which proved to be inefficient and limited its effectiveness. Recently, researchers have developed ‘micromotors,’ or microscale drug delivery systems, combined with insulin-loaded mini-tablets to create a self-propelled system that can efficiently transport insulin to the colon’s lining for absorption.
Researchers from Harvard and MIT have teamed with Novo Nordisk to develop an ingestible device, placed inside a capsule, that can inject insulin into the stomach wall. The self-orienting millimeter-scale applicator (SOMA) autonomously positions itself to engage with GI tissue and then deploys milliposts, or tiny needles fabricated from active pharmaceutical ingredients, directly through the gastric mucosa while avoiding perforation. The capsule dissolves within ten minutes, and the device adheres to the wall of the stomach. The sugar disc breaks apart after a few minutes, allowing the post to penetrate the stomach wall and deliver insulin into the bloodstream. Eventually, the device is naturally excreted. In vivo studies conducted in rats and pigs demonstrated that SOMA is safe and delivers API plasma levels comparable to those achieved with subcutaneous administration.
By incorporating ingestible sensors and other digital components, digitized drugs offer a promising solution for patients and drugmakers. For patients, real-time monitoring and feedback mechanisms facilitate better engagement, empowering individuals to take an active role in managing their health. For drugmakers, the drugs offer valuable data for analysis, a competitive advantage, remote patient monitoring capabilities, and the potential to develop tailored compliance support programs. The advent of digitized drugs also has the potential to address a longstanding challenge in health care — medication nonadherence. Every year, nonadherence contributes to 50% of treatment failures, about 125,000 deaths, and up to 25% of hospitalizations in the U.S. Chronic medication adherence is estimated at only 50% despite treatments requiring 80% for optimal efficacy.
Japan-based Otsuka Pharmaceutical was one of the first companies to employ digitalization to help with adherence. Otsuka’s Abilify MyCite was developed as a digitized version of the antipsychotic medication aripiprazole. Abilify tablets were first approved in 2002 for the treatment of schizophrenia. The ingestible sensor, made by Proteus Digital Health, was added to the tablet which was approved as Abilify MyCite in 2017. The drug’s sensor activates and communicates with a wearable patch worn by the patient. The patch then transmits data to a smartphone application or health care provider’s system, enabling real-time monitoring and verification of medication adherence.
The breakthrough OSD innovation offers health care professionals invaluable insights into patients’ medication-taking behaviors and the ability to tailor treatment plans accordingly.
3D printing of OSD
In the context of OSD, 3D printing, or additive manufacturing, means leveraging 3D printing technology to create customized drugs by depositing layers of pharmaceutical ingredients. “3D printing technology is also making strides in capsule manufacturing. This innovative technique enables the production of complex capsule designs with unique drug release profiles,” says Costa. It offers benefits like personalized dosing, combination therapies, and unique pill designs. However, regulatory frameworks and quality control standards are still developing, and ongoing research aims to optimize the 3D printing process for pharmaceutical applications.
In 2015, Aprecia Pharmaceuticals made history by introducing Spritam, the first FDA-approved 3D-printed drug, designed to treat seizures in individuals with epilepsy. Building on a powder-liquid 3D printing technology initially developed at MIT in the late 1980s, Aprecia developed its approach using print fluids to bind layers of powdered medication into porous tablets using a proprietary conveyor belt-like system called ZipDose. In 2020, Merck KGaG partnered with additive manufacturing specialist AMCM to reimagine tablet production by leveraging the capabilities of 3D printing. The partners utilized powder bed fusion, a technique that involves the melting and fusing of layers of powdered medication using a laser, to create precise and cost-effective 3D-printed tablets.
Their approach promised faster manufacturing and minimized the need for reformulations throughout the development and production process. It also allowed for customization, enabling tablets to be adapted to suit individual patient needs. “With 3D printing, capsules can be customized to deliver drugs with precise release kinetics and even incorporate multiple drugs into a single capsule, offering improved therapeutic options,” says Costa.
Taking flight
The future of OSD formulations continues to hold significant potential for advancement. OSD is poised to continue soaring, revolutionizing patient care through optimized drug formulations and enhanced therapeutic outcomes.
