Polycaprolactone thin-film drug delivery systems: Empirical and predictive models for device design.
OBJECTIVE
To define empirical models and parameters based on theoretical equations to describe drug release profiles from two polycaprolactone thin-film drug delivery systems. Additionally, to develop a predictive model for empirical parameters based on drugs' physicochemical properties.


METHODS
Release profiles from a selection of drugs representing the standard pharmaceutical space in both polycaprolactone matrix and reservoir systems were determined experimentally. The proposed models were used to calculate empirical parameters describing drug diffusion and release. Observed correlations between empirical parameters and drug properties were used to develop equations to predict parameters based on drug properties. Predictive and empirical models were evaluated in the design of three prototype devices: a levonorgestrel matrix system for on-demand locally administered contraception, a timolol-maleate reservoir system for glaucoma treatment, and a primaquine-bisphosphate reservoir system for malaria prophylaxis.


RESULTS
Proposed empirical equations accurately fit experimental data. Experimentally derived empirical parameters show significant correlations with LogP, molecular weight, and solubility. Empirical models based on predicted parameters accurately predict experimental release data for three prototype systems, demonstrating the accuracy and utility of these models.


CONCLUSIONS
The proposed empirical models can be used to design polycaprolactone thin-film devices for target geometries and release rates. Empirical parameters can be predicted based on drug properties. Together, these models provide tools for preliminary evaluation and design of controlled-release delivery systems.
University of California, Berkeley-University of California San Francisco Graduate Program in Bioengineering, CA, USA.
Erica
E
Schlesinger
Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA; BioMarin Pharmaceutical Inc., Novato, CA, USA.
Natalie
N
Ciaccio
University of California, Berkeley-University of California San Francisco Graduate Program in Bioengineering, CA, USA; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
Tejal A
TA
Desai
D065966:Absorption, Physicochemical; D003198:Computer Simulation; D003692:Delayed-Action Preparations / Q000138:chemical synthesis; D004058:Diffusion; D015195:Drug Design; D008422:Materials Testing; D008956:Models, Chemical; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*
D003692:Delayed-Action Preparations; D053769:Nanocapsules; D004364:Pharmaceutical Preparations; D011091:Polyesters; C016240:polycaprolactone
Diffusion; Drug delivery; Empirical; Polycaprolactone