Formulation and dissolution of polymer strip films for the delivery of poorly water-soluble drug nanoparticles

FORMULATION AND DISSOLUTION OF POLYMER STRIP FILMS FOR THE DELIVERY OF POORLY WATER-SOLUBLE DRUG NANOPARTICLES by Scott Matthew Krull Polymer films have emerged as a promising platform for delivery of pharmaceutical products in recent years due to simplified processing, greater flexibility, and improved patient compliance over traditional solid dosage forms. However, the large majority of efforts have focused on incorporation of water-soluble drugs. The objective of this dissertation is to explore the robustness and versatility of the strip film platform for delivery of poorly water-soluble drug nanoparticles to ultimately develop a predictive model for drug release from such films. The robustness of the polymer strip film platform to successfully deliver a variety of poorly water-soluble drug nanoparticles without the need for surfactant is demonstrated first. Drug nanoparticle-loaded films are prepared with and without surfactant for five distinct poorly water-soluble drugs. Fast release is achieved for films made with all five drugs despite differences in water solubility, even in the absence of surfactant, with minimal differences in film quality and properties. Next, various formulation aspects are investigated for their impact on film quality and performance. In one study, three plasticizers at three different concentrations are incorporated into drug nanoparticle-loaded polymer films. A depression in glass transition temperature is observed with increasing plasticizer concentration, along with a corresponding decrease in film tensile strength and increase in film elongation. However, the type and amount of plasticizer used has no significant impact on the dissolution rate of the films, suggesting that film mechanical properties can be effectively manipulated by varying plasticizer concentration with minimal impact on drug release. In another study, three different filmforming polymer molecular weights at three different viscosity levels are used to prepare films containing poorly water-soluble drug nanoparticles. No statistical differences in film tensile strength or elongation at break are observed between films regardless of polymer molecular weight despite requiring up to double the time to achieve 100% drug release, suggesting that film-forming polymer molecular weight can be used to manipulate drug release with little impact on film mechanical properties. The maximum practical drug loading in films is also investigated to address the misconception that strip films are limited to very low dosages. Films made using two film-forming polymer molecular weights are prepared with different concentrations of poorly water-soluble drug nanoparticles by varying the drug loading in the nanosuspension from which the nanoparticles are taken and the polymer-to-nanosuspension mixing ratio. All films up to 50 wt% drug loading show good content uniformity and drug nanoparticle redispersibility, suggesting that high drug loading can indeed be achieved in polymer films, although films tend to become less elastic and more brittle as drug loading increases above 40 wt%. Finally, a mathematical model is developed to predict the rate of drug release from polymer films containing drug particles based on first principles. In summary, various formulation aspects of the polymer strip film platform are investigated for delivery of poorly water-soluble drug nanoparticles and a mathematical model predicting the rate of drug release from such films is developed based on these studies. FORMULATION AND DISSOLUTION OF POLYMER STRIP FILMS FOR THE DELIVERY OF POORLY WATER-SOLUBLE DRUG NANOPARTICLES by Scott Matthew Krull A Dissertation Submitted to the Faculty of New Jersey Institute of Technology in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Chemical Engineering Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering