In vitro release testing of levonorgestrel intrauterine systems: Correlation of accelerated release rates in organic/aqueous release media to Hansen Solubility Parameters.

Rokon Uz Zaman, Coleman Johnson, William Smith, Yan Wang, Ziyue Zhong, Feng Zhang, Xiaoming Xu

Abstract read

In one paragraph

Article in International journal of pharmaceutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed

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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Rokon Uz ZamanOffice of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20903, United States.

Coleman JohnsonOffice of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20903, United States.

William SmithOffice of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20903, United States.

Yan WangOffice of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20903, United States.

Ziyue ZhongDivision of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, University of Texas at Austin, Austin, TX 78712, United States.

Feng ZhangDivision of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, University of Texas at Austin, Austin, TX 78712, United States.

Xiaoming XuOffice of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20903, United States. Electronic address: Xiaoming.Xu@fda.hhs.gov.

Funding

Intramural FDA HHS FD999999

6 · The paper itself

Abstract

Levonorgestrel intrauterine systems (LNG-IUSs) are poly(dimethyl siloxane) (PDMS)-based long-acting drug delivery systems. No generic versions of LNG-IUSs are available; this is due, in part, to challenging aspects of developing and testing these products. One issue is the long timescale of real-time in vitro release tests (IVRTs) and the difficulty of developing accelerated IVRTs. This study developed a correlation between accelerated release rates in organic/aqueous release media and the Hansen Solubility Parameters (HSPs) of LNG, PDMS, and the release media. This study had three parts. First, the LNG-IUS Skyla was analyzed by real-time IVRT and various physicochemical characterization techniques. The purpose of this was to characterize Skyla's release mechanism and develop a model system termed Drug Reservoir-Membrane (DR-M). Second, the HSPs of LNG and PDMS were determined by assessing LNG's solubility and PDMS's swelling in 22 different solvents. This allowed comparison of the HSPs of LNG and PDMS with the HSPs of organic/aqueous accelerated-release media. Third, DR-M samples were tested in accelerated IVRTs and the accelerated release rates were correlated to a novel HSP-based quantity termed HSP Area, which is the triangular area in HSP space between LNG, PDMS, and the tested organic/aqueous release medium. This correlation captured accelerated release rates that were up to nine times faster than the real-time release rate. Additionally, this correlation captured release rates in media with different organic solvents (e.g., ethanol and isopropyl alcohol), and in media with different loadings of organic solvent (e.g., 10%, 20% and 30% organic solvent). We posit that the HSP Area correlation captures two mechanistic effects of the organic/aqueous accelerated-release media: first, this correlation accounts for organic solvent sorption into PDMS and increased drug permeation through PDMS; second; this correlation accounts for increased LNG solubility in the release medium and corresponding increased partitioning of LNG from PDMS into the release medium.

Indexed as

DimethylpolysiloxanesIntrauterine Devices, MedicatedLevonorgestrelDrug LiberationSolubilitySolventsbaysilonDimethylpolysiloxanesLevonorgestrelSolventsHansen solubility parameters (HSP)Intrauterine systems (IUS)In vitro releaseLevonorgestrelPDMSPoly(dimethyl siloxane)Skyla

Identifiers

PMID41856216

DOI10.1016/j.ijpharm.2026.126786

PMCPMC13050559

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.