Technology name
Last update: Apr 2025MZCL Intravaginal Ring
Developer(s)
Type of technology
Intra-vaginal ring
Administration route
Topical (Vaginal)
Development state and regulatory approval
MIV-150 (NNRTI) (MIV-150)
Pre-clinical
Not provided
Description
The MZCL intravaginal ring (IVR) is a multipurpose prevention technology delivering a non-nucleoside reverse transcriptase inhibitor (NNRTI), MIV-150, along with zinc acetate dihydrate, carrageenan, and levonorgestrel. This IVR holds therapeutic potential across multiple areas, including the prevention of HIV, HSV-2, and HPV infections, while also providing hormonal contraception. The device measures 20 mm in diameter and 4 mm in thickness, comprising an ethylene-vinyl acetate (EVA) 40 matrix that encapsulates the APIs. To enable controlled release of the APIs, there is a 500μm pore on sides.
Developer(s)
Population Council
Established in 1952 by John D. Rockefeller III, the Population Council is a nonprofit organization dedicated to biomedical, social science, and public health research. Headquartered in New York City, it operates 18 offices across Africa, Asia, and Latin America, employing nearly 400 staff from 33 countries. The Council has developed contraceptives like the Copper T IUD, Norplant, Jadelle, Mirena.
Technology highlight
1. Multipurpose prevention technology effective against HIV, HSV-2, and HPV. 2. Self-administered for user convenience. 3. Demonstrates superior safety and efficacy in preclinical studies. 4. Functions as a broad-spectrum microbicide and contraceptive.
Illustration(s)
Technology main components
The MZCL intravaginal ring (IVR) contains two regions for controlled release of APIs: the matrix and the core. The matrix, made of translucent ethylene vinyl acetate (EVA-28), holds (i) MIV-150, a non-nucleoside reverse transcriptase inhibitor, and (ii) levonorgestrel, a synthetic progestin for contraception. The core contains (i) carrageenan, a sulfated polysaccharide with antiviral properties, and (ii) zinc acetate, which has antimicrobial activity. This dual-compartment structure enables controlled API release, improving pharmacokinetics and prolonging efficacy. The IVR surface has two pores, 500 μm and 800 μm in diameter, which regulate the release kinetics for sustained drug delivery. This design optimizes therapeutic efficacy for 28 days.
The raw materials for the MZCL IVR are sourced from various manufacturers. Carrageenan is supplied by Industrial Research Limited (Wellington, New Zealand), while zinc acetate is obtained from Spectrum Chemicals (New Brunswick, NJ) and subsequently milled to < 5 μm by Particle Sciences Inc. Levonorgestrel is provided by Crystal Pharma (Valladolid, Spain), and EVA (grade 2803G) is supplied by Celanese (Florence, KY). MIV-150, the anti-HIV agent, is manufactured by Uquifa (Barcelona, Spain). As the MZCL IVR is still under development, it is not yet available for public use.
Safety, Efficacy and Evidence Summary
No adverse events (AE) were identified in the preclinical studies of MZCL Intravaginal ring.
Not provided
Not provided
Not provided
APIs compatibility profile
Small molecules like non-nucleoside reverse transcriptase inhibitors (NNRTIs) and contraceptive hormones are commonly targeted for inclusion in fixed-dose combination intravaginal rings (IVRs).
Not provided
Not provided
75-90 wt%
4 different APIs : The two small-molecule APIs are embedded in the matrix region of the IVR, whereas the large molecules are immersed in the core region.
Min: 2.9 Max: 6.3
Scale-up and manufacturing prospects
Not provided
Hot melt extruder
The IVR Fabrication includes: (i) Using customized molds, Garner Industries melt-extruded the EVA-28 pellets & precompounded them with MIV-150 (± LNG) at 120 psi and 245°F to produce half intravaginal rings (IVRs) with a central core cavity. (ii) The ZA/CG (3/7) mixture was compressed into the core, and the same matrix was extruded on top to form full MZC or MZCL IVRs. (iii) One half contained the core matrix, the other pure matrix. Target loadings were 3 mg MIV-150, 30 mg ZA, 70 mg CG, and 0.6 mg LNG. Leak tests and pore evaluations (500 μm and 800 μm). (iv) API quantification.
(i) Colorimetic UV assay using Methylene blue (ii) High Performance Liquid Chromatography (HPLC)
Excipients & delivery device(s)
No proprietary excipient used
Not provided
Not provided
No delivery device
Additional features
- Monolithic
- Removable
- Single-use
- Reservoir-type
- Room temperature storage
- At least 1 year shelf life
The proof-of-concept study demonstrates that the drug release from the vaginal ring occurs at a controlled rate through the pores within the matrix and core regions, delivering the APIs to the vaginal flora. In vitro studies indicate that the MZCL vaginal ring releases APIs over 94 days, while in vivo studies show a release duration of 28 days. Furthermore, the pharmacokinetic profile of the MZCL IVR was found to be dose-independent.
Not applicable
ICH Climate Zone IV (A/B)
5 years shelf life This product does not require specific temperature storage conditions. Store in the original package to protect from light.
Therapeutic area(s)
- Disease agnostic
- Contraception
- Other(s) : "HPV and HSV-2"
- HIV
- Pre-Exposure Prophylaxis (PrEP)
- Treatment
Potential associated API(s)
- MIV-150 (NNRTI) (MIV-150)
- Levonorgestrel (LNG)
Use of technology
- Self-administered
Monthly
Targeted user groups
- Adults
- Older Adults
- Female
- Cisgender female
- Transgender female
No
No
Yes
Not provided
MIV-150 (NNRTI) (MIV-150)
Non nucleoside Reverse Transcriptase inhibitor
Pre-clinical
Not provided
Prevention of HIV
Not provided
Once monthly
Not provided
Levonorgestrel (LNG)
Hormonal Contraception
Marketed
Not provided
Contraception
Not provided
Once monthly
Not provided
Vaginal ring for drug delivery comprising MIV-150, zinc salt, carrageenan (levonorgestrel mentioned in description)
Disclosed are compositions for inhibiting transmission of a sexually transmitted infection that contain one or more polyanionic microbicides, such as carrageenans, including lambda carrageenan, as well as water-soluble metal salts and specified antiretroviral agents comprising NNRTIs and NRTIs. Also disclosed are methods for making and using the compositions. Also disclosed are intravaginal rings for delivering water-soluble compounds, and preferably high molecular weight water-soluble polymers at essentially a zero order rate. The rings include an outer layer of non-water-swellable elastomer, and preferably high molecular weight water-soluble polymer and an inner layer of the water-soluble polymer, which is imbedded in the outer layer, and an aperture through the outer layer for release.
WO2014123880
Device, Formulations
THE POPULATION COUNCIL, INC.
Not provided
February 4, 2034
Lapsed: AU, BR, CN, EP, IN, RU, ZA
Antimicrobial compositions comprising MIV-150, carrageenans, zinc and levonorgestrel
In a preferred embodiment of the present invention, applicants have thus discovered that the specific combination of the carrageenans of this invention with water-soluble metal salts, preferably such as zinc, as well as the NNRTIs such as MIV-150, are effective in totally blocking vaginal SHIV-RT infection. Compositions of the present invention may also contain a vaginally administrable drug in the aqueous formulation along with the pH controlling agent and the lambda carrageenan or the carrageenans.
WO2011044034
Formulations
THE POPULATION COUNCIL, INC.
Not provided
October 4, 2030
Lapsed: AU, BR, CA, CO, CN, EP, MX, IN, RU, UA, ZA
Antimicrobial compositions comprising carrageenans, zinc and levonorgestrel
Disclosed are compositions for inhibiting transmission of a sexually transmitted infection that contain one or more carrageenans, including lambda carrageenan. Also disclosed are methods for making and using the compositions.
WO2003093322
Formulation
THE POPULATION COUNCIL, INC.
Not provided
April 30, 2023
Expired
MIV-150 compound
Compounds of formula (I): wherein Rx is cyano or bromo; R1 is halo; R2 is C1-C3 alkyl, and pharmaceutically acceptable salts and prodrugs thereof have activity as antiretrovirals.
WO1999036406
Compound
MEDIVIR AB
Patents pertaining to the compound MIV-150 and related methods for making the same are exclusively licensed to The Population Council Inc. by Medivir AB.
January 15, 2019
Expired
