Investigations on the viscoelastic performance of pressure sensitive adhesives in drug-in-adhesive type transdermal films

Purpose We aimed to investigate the effect of solubility parameter and drug concentration on the rheological behaviour of drug-in-adhesive films intended for transdermal application. Methods Films were prepared over a range of drug concentrations (5%, 10% and 20% w/w) using ibuprofen, benzoic acid, nicotinic acid and lidocaine as model drugs in acrylic (Duro-Tak 87-4287 and Duro-Tak 87900A) or silicone (Bio-PSA 7-4301 and Bio-PSA 7-4302) pressure sensitive adhesives (PSAs). Saturation status of films was determined using light microscopy. Viscoelastic parameters were measured in rheology tests at 32°C. Results Subsaturated films had lower viscoelastic moduli whereas saturated films had higher moduli than the placebo films and/or a concentration-dependent increase in their modulus. Saturation concentration of each drug in the films was reflected by decreasing/increasing viscoelastic patterns. The viscoelastic windows (VWs) of the adhesive and drug-in-adhesive films clearly depicted the effect of solubility parameter differences, molar concentration of drug in the adhesive film and differences in PSA chemistry. Conclusions Drug solubility parameters and molar drug concentrations have an impact on rheological patterns and thus on the adhesive performance of tested pressure sensitive adhesives intended for use in transdermal drug delivery systems. Use of the Flory equation in its limiting form was appropriate to predict drug solubility in the tested formulations

Powder properties and their influence on dry powder inhaler delivery of an antitubercular drug

The purpose of this study was to determine if aerosol delivery of drug loaded microparticles to lungs infected withMycobacterium tuberculosis may be achieved by predicting dispersion of dry powders through knowledge of particle surface properties. Particle sizes of rifampicin-loaded poly(lactide-co-glycolide) microparticles (R-PLGA), rifampicin alone, and lactose and maltodextrin carrier particles (bulk and 75-125-μm sieved fractions) were determined by electron microscopy for the projected area diameter (Dp) and laser diffraction for the volume diameter (Dv). Surface energies (Y) of R-PLGA, rifampicin alone, lactose, and maltodextrin were obtained by inverse phase gas chromatography, surface areas (Sa) by N2 adsorption, and cohesive energy densities by calculation. Particle dispersion was evaluated (Andersen nonviable impactor) for 10% blends of R-PLGA and rifampicin alone with bulk and sieved fractions of the carriers. Dp for R-PLGA and rifampicin alone was 3.02 and 2.83 μm, respectively. Dv was 13±1 and 2±1 μm for R-PLGA and rifampicin alone, respectively, indicating that R-PLGA was more aggregated. This was evident in Y of 35±1 and 19±6 mJ/m2 for R-PLGA and rifampicin alone. Dp for lactose and maltodextrin (sieved and bulk) was approximately 40 mm. Bulk maltodextrin (Dv=119±6 mm) was more aggregated than bulk lactose (Dv=54±2 mm). This was a result of the higher Sa for maltodextrin (0.54 m2/g) than for lactose (0.21 m2/g). The Y of bulk lactose and maltodextrin was 40±4 and 60±6 mJ/m2 and of sieved lactose and maltodextrin was 39±1 and 50±1 mJ/m2. Impaction studies yielded higher fine particle fractions of R-PLGA from sieved lactose, 13%±3%, than from sieved maltodextrin, 7%±1%, at 90 L/min. An expression, based on these data, is proposed as a predictor of drug dispersion from carrier particles