(T1130-12-70) Development and Evaluation of Polyvinylpyrrolidone and Chitosan-Based Film Forming Gel containing Acyclovir

Purpose: The purpose of this study was to use Polyethylene glycol 600 (PEG 600) as a crystallization inhibitor in a film-forming gel (FFG) film as a novel approach to enhance the skin permeability and bioavailability of poorly water-soluble acyclovir.

Methods: The novel acyclovir-loaded FFG was composed of acyclovir, chitosan, polyvinylpyrrolidone (PVP), PEG 600, lactic acid at a weight ratio 1/1.5/0.5/3/2 prepared by making physical mixture. This preparation is compared in terms of its film formation time, physicochemical properties including molecular interaction features and in-vitro permeability. The film formation time is considered as the measured time when the gel (0.2 g) was completely dried on Petri dish (3 cm x 4 cm) at 35 °C. The modulus of elasticity, tensile strength and elongation at break and Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC), X-ray diffraction (XRD) also conducted as physicochemical properties. In-vitro skin permeation study was performed by using Franz diffusion cells with Phosphate buffer (pH = 7.4) and its temperature maintained at 37 °C.

Results: This FFG turns into a film through evaporation of the solvent after application to the skin with the least crystallization as shown in Fig. 1 and Fig. 2. Acyclovir-loaded FFG transforms crystalline drug to an amorphous state with no molecular interactions were observed in the FFG film as shown in Fig. 2. Compared to the film form, FFG is easier to use and apply and especially simpler to manufacture. Compared to the other formulations, the film formation time of PVP and chitosan-based FFG was only 4.6 min which is the fastest. Plus, FFG with PVP and chitosan in a ratio of 0.5/1.5 reduced the film formation time and revealed the lowest Young’s modulus. PVP and chitosan-based FFG added 3% PEG 600 showed the highest drug permeation. Compared to the commercial product and acyclovir-loaded FFG film significantly enhanced drug permeability (8.7 vs. 50.2 μg/cm² at 24 hours) as shown in Fig. 3.

Conclusion: Therefore, FFG film is a novel potential system in dosage forms used on the skin for improving the mechanical properties and the skin permeability of acyclovir. It shows also better appearance when the FFG was completely dried after application to the skin because its transparent characteristic.

Fig. 1. ACV-loaded FFG during film formation: (A), initial state; (B), 10 min after application.



Fig. 2. (A) FT-IR spectra, (B) DSC graphs and (C) XRD patterns: (a), ACV powder; (b), chitosan; (c), PVP; (d) ACV-loaded FFG film (formulation I); (e) ACV-loaded FFG film (formulation IV).



Fig. 3. Skin permeation profiles of ACV-loaded FFG. The ACV-loaded FFGs were composed of acyclovir, chitosan, PVP, PEG600, lactic acid, water, and ethanol.