Effect of solvents and cellulosic polymers on quality attributes of films loaded with a poorly water-soluble drug.

The combined effect of solvent, cellulosic polymer, and a poorly water-soluble drug, fenofibrate (FNB) on solution-cast pharmaceutical film quality attributes, e.g., morphology, drug recrystallization, content uniformity, mechanical properties, dissolution rate and supersaturation level, was investigated. Film morphology, content uniformity, and mechanical properties were impacted by the extent of FNB recrystallization which was strongly affected by FNB solubility in the solvent as compared to the polymer type, hydroxypropyl methylcellulose or hydroxypropyl cellulose. FNB recrystallization affected drug dissolution rates and supersaturation under non-sink conditions. Specifically, the area under the curve linearly correlated with recrystallization. After one-year storage, FNB recrystallization reached very high levels even for the films with no initial recrystallization, suggesting low initial crystallinity does not guarantee stability. Thus, uncontrolled recrystallization and poor time-stability would be unavoidable for solution-cast films. Overall, both the polymer and the solvent strongly impact drug recrystallization, film structure, mechanical properties, dissolution rate, and supersaturation.

Efavirenz nanomicelles loaded vaginal film (EZ film) for preexposure prophylaxis (PrEP) of HIV.

Preexposure prophylaxis (PrEP) using oral or vaginal microbicide is an emerging and effective strategy to prevent HIV transmission. Vaginal film is becoming more acceptable and a convenient dosage form compared to cream, gel and suppository. Extremely poor aqueous solubility of efavirenz (EFV) limits its use as vaginal microbicide. The aim of this study was to develop and evaluate a monomeric surfactant free, rapidly soluble vaginal film of EFV (EZ film). EZ film was prepared using a tetrafunctional block polymer (Tetronic 1107), carrageenan and polyvinyl alcohol (PVA) by solvent evaporation method. First, different solubilizers were screened for EFV solubility, in vitro cytotoxicity and cell membrane integrity assay on HeLa cells. Optimized film was characterized for solid state, mechanical strength, epithelial integrity, in vitro drug release in simulated vaginal fluid (SVF), simulated seminal fluid (SSF) and in vitro anti-HIV activity. Optimized EZ film showed a particle size of 48 ±â€¯3.8 nm with PDI of 0.299. Differential scanning colorimetry (DSC) thermogram suggested the complete amorphization of EFV within the film. EZ film rapidly disintegrated (30 s) with complete release of EFV in SVF and SSF. The film was found to be non-toxic to HeLa cells and showed similar anti-HIV-1 activity as that of EFV in DMSO. EZ film did not show any significant change in the TEER value in HEC 1A cell line. Hence, the findings from the current study strongly suggest that the EZ film could be a cost-effective and convenient dosage form for PrEP of HIV.

A predictive transport model for convective drying of polymer strip films loaded with a BCS Class II drug.

Drying is an important unit operation in the manufacturing of polymer strip films as it affects various film quality attributes. Optimal design and control of convective drying process require models that capture the impact of critical process parameters such as air temperature and velocity on the temporal evolution of film thickness and moisture. Here, a detailed transport model was presented to capture moisture diffusion, heat transfer and moving boundary in convective drying of polymer strip films loaded with griseofulvin (GF), a poorly water-soluble drug. It incorporates a solvent diffusivity model based on free-volume theory. Experimentally, film precursor suspensions were prepared by mixing silica-coated and micronized GF powder with an aqueous solution of hydroxypropyl methylcellulose (HPMC)-glycerin. Films were cast and moisture-time variation during drying was measured. The transport model, whose diffusivity parameters were estimated using drying data at a reference condition, was validated at different drying conditions and wet film thicknesses. It delineates underlying mechanisms of drying kinetics and demarcates a smooth transition from constant-rate to falling-rate period. Overall, our results suggest that the transport model is capable of predicting the temporal evolution of moisture and final film thickness at different drying air velocities and temperatures with reasonable accuracy.