Formulation and Characterization of Polymeric Films Containing Combinations of Antiretrovirals (ARVs) for HIV Prevention

Abstract

Purpose To develop polymeric films containing dual combinations of anti-HIV drug candidate tenofovir, maraviroc and dapivirine for vaginal application as topical microbicides. Methods A solvent casting method was used to manufacture the films. Solid phase solubility was used to identify potential polymers for use in the film formulation. Physical and chemical properties (such as water content, puncture strength and in vitro release) and product stability were determined. The bioactivity of the film products against HIV was assessed using the TZM-bl assay and a cervical explant model. Results Polymers identified from the solid phase solubility study maintained tenofovir and maraviroc in an amorphous state and prevented drug crystallization. Three combination film products were developed using cellulose polymers and polyvinyl alcohol. The residual water content in all films was < 10% (w/w). All films delivered the active agents with release of > 50% of film drug content within 30 minutes. Stability testing confirmed that the combination film products were stable for 12 months at ambient temperature and 6 months under stressed conditions. Antiviral activity was confirmed in TZM-bl and cervical explant models. Conclusions Polymeric films can be used as a stable dosage form for the delivery of antiretroviral combinations as microbicides.

Griffithsin-Modified Electrospun Fibers as a Delivery Scaffold To Prevent HIV Infection

“…Similarly, for intravaginal films, user adherence is a common barrier to obtaining efficacy and is impacted by the perceived difficulty of film administration, as well as localized irritation after prolonged contact (76,77). Furthermore, the rapid and complete release of the incorporated agents from intravaginal films within hours of administration may result in transient protection against STIs, thereby remaining a major hurdle to obtaining long-term delivery and efficacy (78,79).…”

Safety and Pharmacokinetics of Quick-Dissolving Polymeric Vaginal Films Delivering the Antiretroviral IQP-0528 for Preexposure Prophylaxis

“…Vaginal films containing the IQP-0528 nanoparticles (IQP-0528NP) and vaginal films containing unencapsulated IQP-0528 (IQP-0528) were manufactured through the solvent casting and evaporation method as previously described (34,46). Briefly, the polymeric film excipients were mixed in a water solution, followed by the addition of 1.5% (film, wt/wt) IQP-0528 or the equivalent drug concentration of IQP-0528 nanoparticles.…”

“…The polymeric solution was cast into thin sheets on an Elcometer 4340 automatic film applicator (Elcometer, Rochester Hills, MI) to evaporate the solvents, resulting in the final quick-dissolving polymeric film. The physicochemical properties of the films were determined as previously described and had the following characteristics: area, 1,200 mm 2 ; mass, 235 Ϯ 4 mg; opaque white appearance and smooth and pliable texture; thickness, 0.22 Ϯ 0.01 mm; visual disintegration time, 8.6 Ϯ 1.5 min; water content, 4.635% Ϯ 0.049%; tensile strength, 9.675 Ϯ 0.330 N; puncture strength, 6.710 Ϯ 0.454 N; dissolves at pH 7 (34). The dissolution of the films was pH independent and controlled by the vaginal fluid volume.…”

“…The in vitro release of IQP-0528 (1.5%, wt/wt) from the quick-dissolving films and the nanoparticle-encapsulated (1.5%, wt/wt drug equivalent) quick-dissolving films was evaluated in a USP 4 apparatus (Sotax CP 7) as previously detailed (34,41). The flow rate was set to 15 ml/min at a temperature of 37°C.…”

“…Vaginal films to treat bacterial vaginosis and vaginal candidiasis have also been developed (26,27). A number of promising ARVs and/or microbicides, such as dapivirine, TFV, dapivirine in combination with TFV and maraviroc, retrocyclin-101, and cellulose acetate phthalate, have been formulated into films (28)(29)(30)(31)(32)(33)(34). A few studies have evaluated the safety, pharmacokinetics (PK) and pharmacodynamics of films in macaques and humans (29,35).…”