# Rationally designed lipid- and food-based drug formulations to enhance oral bioavailability

> **NIH NIH R43** · MECHASIM INC. · 2021 · $251,316

## Abstract

Abstract
More than 40% of marketed drugs and about 90% of drugs in development pipelines suffer from poor aqueous
solubility and associated low bioavailability. Food, and lipids in particular, can significantly enhance the
bioavailability of such drugs. This “food effect” could be exploited by developing lipid- and food-based
formulations that demonstrate enhanced efficiency absorption, and as a result can be designed at a reduced
drug dose while maintaining the same systemic exposure. Notably, using food components as formulation
excipients would also mitigate food effects on bioavailability, thus allowing patients to take these medications
irrespective of food, reducing the complexity of medication regiments, and ultimately addressing the significant
issue of low patient adherence. However, lipid and food use in oral drug delivery is limited, in part, due to lack of
ability to predict a priori lipid function in the GI tract and its effect on drug absorption. Our team has developed
an algorithm that can predict the impact of food quantity and composition on drug absorption and bioavailability
from a mechanistic point of view. Specifically, our algorithm considers multiple parallel, dynamic processes (drug
dissolution, lipid and protein digestion, drug partitioning in colloids, absorption) to quantitatively predict the impact
of food-associated lipids and proteins on oral bioavailability. This approach offers tremendous value by enabling
rational quantitative guidance in developing improved dosage forms using lipids and other food ingredients as
formulation excipients. In this project, we aim to develop novel formulations of a poorly bioavailable oral marketed
drug that is known to be significantly impacted by food and is restricted to be taken only after a meal. The novel
dosage forms will demonstrate enhanced capabilities in that they can be administered at a lower dose for the
same therapeutic effect and administration with or without food will not impact bioavailability. Development of
these formulations will demonstrate the practical application of our algorithm to improve oral delivery of poorly
bioavailable drugs by exploiting the food effect. In the first aim, the existing algorithm will be adapted to predict
drug pharmacokinetics after administration of an aqueous lipid/protein emulsion-based delivery vehicle. Kinetic
parameters will be measured in vitro and used as model input parameters to inform selection of the most optimal
drug dose and lipid-protein mixture composition that is bioequivalent to the marketed formulation. In the second
aim, the modeling framework will be employed to select a lipid-surfactant-cosolvent system that can be
administered as a lipid-based formulation inside a capsule. Formulation parameters (e.g., drug dose, excipient
composition) will be optimized to inform development of a formulation that is bioequivalent to the marketed
dosage form. Bioequivalence among all formulations will be demonstrated via pharmaco...

## Key facts

- **NIH application ID:** 10157659
- **Project number:** 1R43GM140759-01
- **Recipient organization:** MECHASIM INC.
- **Principal Investigator:** Rebecca L Carrier
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $251,316
- **Award type:** 1
- **Project period:** 2021-09-27 → 2023-12-26

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10157659

## Citation

> US National Institutes of Health, RePORTER application 10157659, Rationally designed lipid- and food-based drug formulations to enhance oral bioavailability (1R43GM140759-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10157659. Licensed CC0.

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