1. Methodological comparison and in vitro/in vivo prediction of dissolution assays (methodological validation literature)

• Source : International Journal of Pharmaceutics 561 (2019) 124–134.

• Authors and Institutions : Isabell Speer, Maren Preis, Jörg Breitkreutz (Institute of Pharmacy and Biopharmaceuticals, University of Düsseldorf, Germany / Öster University, Finland)

• Core Title : Dissolution testing of oral film preparations: Experimental comparison of compendial and non-compendial methods

• Core Technology Essentials :

  • Cross-sectional evaluation of four dissolution methods : systematic comparison basket method (USP 1, 100 rpm), paddle and glass disc method (PGD, USP 2, 50 rpm), flow cell with 3D printed sample holder (FTC + FH3D, USP 4, 8 mL/min), and punch and filter method (PAF, 14g simulated tongue pressure + 0.25 mL/30s simulated saliva).

  • Differences in Discriminatory Power :

    • For double-layer barrier membranes (ODF-DL), FTC + FH3D (MDT80 = 366.8 min) and PGD paddle method (MDT80 = 217.1 min) have extremely high identification power and can accurately monitor the integrity of the barrier layer; while traditional basket method and PAF cannot effectively distinguish between instantaneous and double-layer membranes due to mesh blockage or operational limitations.

    • The FTC + FH3D sample chamber's tiny volume (approximately 3 mL) perfectly matches the physiological saliva volume in the human mouth and has the ability to programmatically change media, making it the best tool for simulating gastrointestinal transit (GI transit) and in vivo-in vitro correlation (IVIVC).

2. Oral dissolving film prescription design, manufacturing process and physical property characteristics (global R&D review)

• Reference : Turk J Pharm Sci 2021; 18(1): 111-121.

• Authors and Institutions : Rukiye Sevinç Özakar, Emrah Özakar (Department of Pharmacy Technology, Faculty of Pharmacy, University of Atatürk)

• Core Title : Current Overview of Oral Thin Films

• Core Technology Essentials :

  • Key formulation components (Formulation Q1/Q2) : Systematic analysis of film-forming polymers (HPMC, Pullulan, PVA, 40–50%), plasticizers (Glycerin, PEG, 0–20% for their effects on reducing glass transition temperature (Tg) and improving flexibility), superdisintegrating agents (2–8%), salivating agents (2–6%), and taste-masking mechanisms.

  • Commercial manufacturing process comparison : A detailed comparison of the advantages and disadvantages of solvent casting (film thickness 12–100 µm, excellent thickness uniformity, avoidance of thermal API degradation), hot melt extrusion (HME), and rolling method.

  • Key physical properties and CQA characterization :

    • Mechanical toughness : Folding endurance (greater than or equal to 300 times is rated as excellent toughness), tensile strength, and elongation at break (% Elongation).

    • Disintegration and dissolution assessment : small volume culture dish method (2–7 mL medium to simulate tongue vibration, disintegration time within 5–30 seconds) and Franz diffusion cell/paddle plate fixation technique.

3. Official Drug Administration Review Standards and Industrialization Application Guidelines (Regulatory Guidelines)

• Issuing Authority : Center for Drug Evaluation (CDE, NMPA) of the National Medical Products Administration

• Effective date : July 2025 (trial implementation)

• Core Title : Technical Guidelines for Pharmaceutical Research of Orally Disintegrating Films of Chemical Drugs (Trial Implementation)

• Core Technology Essentials :

  • QTPP and CQA specifications clearly define the appearance, thickness uniformity, mechanical properties (tensile strength, elongation at break, folding endurance), dissolution time (requires simulation of small-volume clinical media and verification of in vitro-in vivo correlation), and dissolution rate (recommended flow cell method or paddle disc method) as core control items.

  • Full-process control of key process parameters (CPP) :

    • Solution preparation and degassing : Strictly monitor the parameters of static setting, vacuum centrifugation, or vacuum stirring for degassing to prevent uneven content caused by microbubble residue.

    • Coating and drying : Strictly monitor the liquid inlet speed, squeegee gap height, drying air temperature, and calculate the slitting/cutting area.

  • Packaging and Commercialization Requirements :

    • Emphasis is placed on high-barrier composite rigid packaging materials (such as polyester/aluminum/polyethylene, paper/aluminum/polyethylene), and easy-open and child-proof tear-resistant designs are evaluated.

    • Commercial production batches are generally recommended to be no less than 100,000 dosage units ; generic drugs need to be compared with reference formulations (RLDs) in terms of quality and stability during the full shelf life and in-use at extreme temperatures and humidity.

II. Chinwei Technology's Perspective: Development of Orally Disintegrating Film Formulations and In Vitro Dissolution Evaluation Technology

In the development of oral films (ODF/MBF) and reverse engineering of generic drugs, the most common challenges faced by the industry are: after the film is placed in the dissolution vessel, it is very easy to generate electrostatic adsorption, float on the liquid surface, or directly adhere to the vessel wall/blade dead zone , resulting in false release delay or extremely poor repeatability (%RSD); in addition, the traditional USP 1 basket method often causes the 40 mesh pores to be blocked by the viscous gel formed by polymer hydration, resulting in a serious underestimation of dissolution.

III. References and Documents

• NMPA CDE — "Technical Guidelines for Pharmaceutical Research on Oral Dissolving Films of Chemical Drugs (Trial Implementation)", July 2025.

• US FDA — Guidance for Industry: Orally Disintegrating Tablets, Center for Drug Evaluation and Research (CDER).

• USP-NF 2024 General Chapters <711> — Dissolution, United States Pharmacopeial Convention.

• USP-NF 2024 General Chapters <1151> — Pharmaceutical Dosage Forms, United States Pharmacopeial Convention.

• Ph.Eur. 11.5 General Chapters <1807> / <2.9.40> — Oromucosal Preparations / Uniformity of Dosage Units, European Directorate for the Quality of Medicines (EDQM).

• Speer, I., Preis, M., Breitkreutz, J. (2019). Dissolution testing of oral film preparations: Experimental comparison of compendial and non-compendial methods. International Journal of Pharmaceutics, 561, 124–134.

• Sevinç Özakar, R., Özakar, E. (2021). Current Overview of Oral Thin Films. Turkish Journal of Pharmaceutical Sciences, 18(1), 111–121.

• Krampe, R., Sieber, D., Pein-Hackelbusch, M., Breitkreutz, J. (2016). A new biorelevant dissolution method for orodispersible films. European Journal of Pharmaceutics and Biopharmaceutics, 98, 20–25.