Category: Formulation and Quality
Purpose: The scope of the present work is to develop and investigate a novel delivery system for the skin as alternative to the existing transdermal dosage forms. The approach chosen for the new dosage form is a polymeric bio-adhesive film forming topical spray. On the skin surface the solution solidifies into a film which is able to deliver the active moiety to the body.
Methods: For this work film forming preparations are defined as non-solid dosage forms that produce a substantial film in situ after application on the skin or any other body surface. Such compositions can either be liquids or semisolids with a film forming polymer as basic material for the matrix. The formed film is sufficiently substantial to provide a sustained drug release to the skin. Film forming polymeric solutions as a novel approach for skin drug delivery were developed and concerning their mechanical properties and rate of drug permeability. They were developed by varying type and content of the film forming polymer as well as nature and content of the permeation enhancers. The resulting formulations were evaluated according to five criteria: drying time, cosmetic attractiveness, outward stickiness, integrity on skin and drug permeability. Drug rerelease from a series of formulations was assessed in vitro. Synthetic membrane, MatTek’s EpiDerm Skin and cadaver skin was used in permeation experiments with Franz diffusion cells. The spray pattern, pump seal efficiency, average weight per metered dose and dose uniformity were evaluated to optimize the formulation.
Results: Film forming solutions were successfully formulated with polymers from different chemical groups such as acrylates (Eudragit® RL PO, Eudragit® S 100, Eudragit® NE 40D, Eudragit® E 100), cellulose derivatives (Methocel LV, Klucel® LF), polyvinylpyrrolidones (Kollidon® VA 64) and silicones (SGM 36). These formulations contained one of the polymers, a permeation enhancer, a volatile solvent and other optional excipients. An optimized formulation containing 10%(w/v) drug, 5% (w/v) permeation enhancer and 80 %(w/v) ethanol was based on good skin permeation and acceptable drug concentration. When optimized formulation tested for cumulative drug permeation per cm2 from a Mattek and human cadaver skin membrane, over the first two hours, the drug permeation ranged from 10 μg/cm2 to 500 μg/cm2 and over 24 hours, the drug permeation ranged from 10 μg/cm2 to 6500 μg/cm2. The second slower phase of drug release observed between 2 – 24 hours after spray application indicates that drug gradually permeates from the polymeric bio-adhesive film in a controlled manner. Results showed that the 10% of the spray droplets have a mean diameter of about 26 μm ± 20 μm, about 50% of the spray droplets have a mean diameter of about 55 μm ± 20 μm, and about 90% of the spray droplets have a mean diameter of about 116 μm ± 40 μm. The results indicated that the drug showed reproducible amounts of the formulation per actuation with the standard deviation of 0.6 variance.
Conclusion: The present work has demonstrated that film forming solutions for the application on the skin can be formulated with a variety of excipients, but that the selection of the excipients has to be performed with care. The potential of the film forming solutions as drug delivery systems has been shown in comparative permeation experiments with commercially available transdermal patches. From the results obtained in this work it can be concluded that the metered dose transdermal spray has potential as an alternative therapeutic system for the transdermal delivery of drugs.