The three in vitro methods answer different questions and are not interchangeable. Dissolution, disintegration, or drug-release testing may be used for oral dosage forms depending on the dosage form and applicable requirements. IVRT (in vitro release test) measures how fast the drug is released from a topical product into a receiving medium across an artificial membrane. IVPT (in vitro permeation test) measures how fast the drug permeates through skin, and therefore uses skin as the barrier. For oral films, in vitro release or dissolution testing may be used as part of product evaluation depending on the formulation and applicable requirements; for transdermal products, release and permeation studies may be used for product development, quality assessment, or equivalence evaluation depending on the product and regulatory pathway.
Choosing the method
| Method | What it measures | Barrier | Typical use |
|---|---|---|---|
| Dissolution / release testing | Rate of drug release from the dosage form into a test medium | None – the dosage form is the subject | Oral dosage forms; product evaluation and quality control, as applicable |
| IVRT | Rate of drug release from the product | Artificial membrane | Topical products; method development, equivalence assessment, or quality evaluation as applicable |
| IVPT | Rate of drug permeation through skin | Skin | Formulation development, permeation comparison, or equivalence support as applicable |
Apparatus and conditions are method-specific
- IVRT and IVPT apparatus: vertical diffusion cells (Franz-type) are commonly used for IVRT and IVPT, while other apparatus may also be appropriate depending on the dosage form and method. The receptor medium, temperature and stirring rate need to be selected and controlled to provide a suitable and discriminating test while maintaining appropriate sink conditions.
- Sink conditions: a commonly used rule of thumb is to keep the drug concentration in the receptor medium below about 10 per cent of its saturation solubility. The exact criterion may vary depending on the method, drug substance and receptor medium.
- Skin and membranes: excised human skin is a reference model for IVPT, but supply is limited and its handling needs to be standardised. Synthetic membranes such as Strat-M can be useful for early formulation screening, but they should not be treated as a replacement for biological skin in IVPT.
Watch the scope of each guideline
Regulatory scope differs, and using a guideline outside its scope can lead to inappropriate study design or regulatory interpretation. In China, the IVRT and IVPT guideline issued as CDE Notice No. 22 of 2025 applies to locally acting generic chemical drugs in semi-solid topical dosage forms, such as ointments, creams and gels. Transdermal and topical delivery systems are addressed by separate guidance, including FDA’s 2019 draft guidance on product development and quality considerations for these systems. A transdermal patch therefore needs to be evaluated under the applicable transdermal delivery system framework rather than automatically applying the semi-solid IVRT and IVPT framework.
Equipment implications
Aligned Machinery was founded in 2004 and operates its production base in Zhejiang Province. The company has more than 68 independently developed patents and serves more than 550 companies in over 100 countries. It entered the oral dissolving film equipment market in 2018 and also supplies transdermal patch line equipment. CE documentation is available for the products supplied, and equipment is designed in line with GMP requirements.
For development work, laboratory casting equipment can produce the film or patch samples used in release and permeation studies, while formulation testing services can generate the sample series required for method development.
FAQ
What is the difference between IVRT and IVPT?
IVRT measures how fast the drug is released from a topical product into a receiving medium across an artificial membrane. IVPT measures how fast the drug permeates through skin, so it uses skin as the barrier. Release reflects drug movement out of the product, while permeation also involves passage through the skin barrier.
When is dissolution or release testing used instead?
For oral dosage forms, dissolution, disintegration, or drug-release testing may be used depending on the formulation, dosage form, and applicable compendial or regulatory requirements.
What is the sink condition rule in diffusion cell testing?
A commonly used rule of thumb is to keep the drug concentration in the receptor medium below about 10 per cent of its saturation solubility. The exact criterion may vary depending on the method, drug substance and receptor medium.
Can an artificial membrane replace skin in IVPT?
Not as a replacement for skin in IVPT. Synthetic membranes can be useful for early formulation screening, but they do not reproduce all properties of biological skin.
Which guideline applies to a transdermal patch?
A transdermal patch should be evaluated under the applicable transdermal and topical delivery system framework and relevant product-specific guidance. China’s 2025 IVRT and IVPT guideline applies to locally acting generic semi-solid topical products, such as ointments, creams and gels, rather than serving as a general guideline for transdermal patches.
References
[1] Merck (Sigma-Aldrich), “Strat-M Membrane” application brochure (manufacturer documentation; data on 21 compounds and 8-hour cumulative permeation). https://www.sigmaaldrich.cn/deepweb/assets/sigmaaldrich/marketing/global/documents/121/128/strat-m-membrane-br2545en-ms.pdf
[2] China Center for Drug Evaluation (CDE), “Technical Guideline for In Vitro Release Test (IVRT) and In Vitro Permeation Test (IVPT) Studies of Locally Acting Generic Chemical Drugs (Interim),” Notice No. 22 of 2025, applicable to locally acting generic chemical drugs in semi-solid topical dosage forms. https://www.cde.org.cn/main/news/viewInfoCommon/114aa83096de4873146fc035b0f6f747
[3] China Center for Drug Evaluation (CDE), “Technical Guideline for Clinical Trials of Adhesion and Irritation/Sensitization Assessment of Generic Transdermal and Local Delivery Systems (Interim),” Notice No. 14 of 2026, issued and effective 29 January 2026. https://www.cde.org.cn/main/news/viewInfoCommon/16d9dbfe96cf3d22631670bdf6b763b1
[4] Aligned Machinery, “Transdermal Patch Production Line.” https://www.odfsolution.com/transdermal-patch-mfg-machine/
Post time: Aug-13-2026