(i) HEC: HMC: CMC [or] HEC: HPMC: NaCMC (at varying concentrations) (ii) Plasticizer (eg: glycerin, polyethylene gylcol monomethyl ether, propylene glycol, sorbitol sorbitan solution, castor oil) (iii) Dispersant (iv) Humectant (v) Disintegrant (eg: PEG 400, PEG 6000; PEG 8000) (v) Solubilizing/ alkalizing agent (eg: sodium hydroxide)

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A Phase 1 clinical trial involving 78 healthy volunteers demonstrated that 91% of participants experienced solely Grade 1 adverse events (AEs). These AEs were evenly distributed across both the film tenofovir treatment and film placebo control groups, indicating a favourable safety and tolerability profile for the film formulation. Nevertheless, adherence challenges were reported by 50% of the study population.

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1) Elcometer 4340 Motorised/Automatic Film Applicator, Mixing vessels (with vacuum applicator) 2) Metrohm, 758 KFD Titrino 3) Coating and drying vessels 4) Packaging instrumentations (not specified)

The manufacturing of vaginal films using a Hot Melt Extrusion Process requires a cleanroom environment and involves several key steps: Feeding: Selected materials are introduced into an extruder. Melting: In the extruder, materials are heated to a temperature where polymers melt—above their melting point but below their decomposition temperature. Mixing: The molten material is mixed thoroughly to ensure even distribution of the API and excipients. Extrusion: The uniform mixture is extruded through a die to form a continuous sheet or film. Cooling: Extruded film is cooled rapidly to solidifies.

1) X-ray diffraction (To examine solid state solubility) 2) TX-XT Plus texture analyser 3) UPLC

No proprietary excipient used

No novel excipient or existing excipient used

No residual solvent used

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• Biodegradable
• Drug-eluting
• Non-removable
• Reservoir-type
• Room temperature storage

Preclinical data indicate sufficient dissolution and drug release properties for a range of antiretroviral agents within the film matrix. Notably, a single-dose study of a 40 mg tenofovir (TFV) film demonstrated superior TFV delivery compared to the TFV vaginal gel formulation. Plasma and cervicovaginal fluid TFV concentrations were elevated on day 1 following TFV film administration compared to the gel, though levels converged by days 3 and 7 days later.

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A six-month accelerated stability test was conducted at 40°C to evaluate the integrity of vaginal films produced via hot melt extrusion. The results demonstrated that the weight of the films remained stable over the testing period. Variability in water content and puncture strength was found to be insignificant, indicating robust physical properties. The films with tenofovir showed good compatibility with various strains of lactobacilli as well.

Preclinical stability studies demonstrated no loss of API from vaginal films stored at 30, 40, and 50°C for 14 days. However, further investigation of storage conditions is warranted to establish long-term stability at cold storage conditions.