# In Vitro Based Approaches to Evaluate the Bioequivalence of Locally-Acting Rectal and Vaginal Semi-Solid Drug Products

> **NIH FDA U01** · UNIVERSITY OF RHODE ISLAND · 2022 · $250,000

## Abstract

ABSTRACT
Locally-acting rectal and vaginal semi-solid products have been widely used for the treatment of diseases and
disorders in the rectum and vagina (and/or cervix) over the past few decades. Despite their prevalence, the
development and approval of generic versions of these drug products have remained difficult due to the
complexity of these products as well as the challenges of conducting bioequivalence (BE) studies with clinical
pharmacodynamic (or pharmacokinetic) endpoints. The main objectives of the project are to: 1) identify critical
quality attributes (CQA’s) of a variety of semi-solid dosage forms (such as suppositories with/without a gelatin
coating and creams) that are common for rectal and vaginal administration; 2) develop in vitro performance test
methods and method validation strategies that are unique for these rectal and vaginal products; and 3) elucidate
drug permeation mechanisms across the rectal and vaginal mucosal membranes. The proposed research builds
upon our previous research on the comparative product characterization and method development and validation
of in vitro performance tests (such as in vitro release test (IVRT) and in vitro permeation test (IVPT)) for rectal
suppositories and vaginal creams. Miconazole nitrate that is commercially available in a variety of vaginal dosage
forms (i.e., suppository with/without a gelatin coating, cream) and mesalamine will be used as the model drugs.
Comprehensive characterization of relevant physicochemical and structural properties of a variety of semi-solid
dosage forms prevalent for rectal and vaginal administration will be conducted. The quality-by-design (QbD)
principles will be implemented to identify CQA’s as well as the key material and processing parameters that can
affect the CQA’s and in vitro product performance for a variety of topical rectal and vaginal semi-solid dosage
forms. In vitro permeation behavior of a variety of topical semi-solid dosage forms and drugs (e.g., hydrophilic
vs. hydrophobic) will be investigated using both animal and human tissues to elucidate drug permeation
mechanisms across the mucosal membranes. Lastly, a pilot study on expanding physiologically based
pharmacokinetic (PBPK) modeling to support BE assessment of locally-acting rectal and vaginal drug products
will be conducted. It is expected that a comprehensive understanding of the CQA’s and their relationship to
material and processing differences will be provided for a variety of topical semi-solid dosage forms. Moreover,
robust and sensitive in vitro performance test methods and method validation strategies that are unique for rectal
and vaginal products will be developed. The proposed research will support the establishment of in vitro
comparative product characterization-based BE approaches that are suitable for locally-acting rectal and vaginal
semi-solid drug products, thus facilitating the development of generic versions of these drug products and helping
advance the regul...

## Key facts

- **NIH application ID:** 10599677
- **Project number:** 1U01FD007656-01
- **Recipient organization:** UNIVERSITY OF RHODE ISLAND
- **Principal Investigator:** Jie Shen
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2022
- **Award amount:** $250,000
- **Award type:** 1
- **Project period:** 2022-09-15 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10599677

## Citation

> US National Institutes of Health, RePORTER application 10599677, In Vitro Based Approaches to Evaluate the Bioequivalence of Locally-Acting Rectal and Vaginal Semi-Solid Drug Products (1U01FD007656-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10599677. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*