Experimental and computational analysis of a pharmaceutical-grade shape memory polymer applied to the development of gastroretentive drug delivery systems.

The present paper aims at developing an integrated experimental/computational approach towards the design of shape memory devices fabricated by hot-processing with potential for use as gastroretentive drug delivery systems (DDSs) and for personalized therapy if 4D printing is involved. The approach was tested on a plasticized poly(vinyl alcohol) (PVA) of pharmaceutical grade, with a glass transition temperature close to that of the human body (i.e., 37 °C). A comprehensive experimental analysis was conducted in order to fully characterize the PVA thermo-mechanical response as well as to provide the necessary data to calibrate and validate the numerical predictions, based on a thermo-viscoelastic constitutive model, implemented within a finite element framework. Particularly, a thorough thermal, mechanical, and shape memory characterization under different testing conditions and on different sample geometries was first performed. Then, a prototype consisting of an S-shaped device was fabricated, deformed in a temporary compact configuration and tested. Simulation results were compared with the results obtained from shape memory experiments carried out on the prototype. The proposed approach provided useful results and recommendations for the design of PVA-based shape memory DDSs.

Retentive device for intravesical drug delivery based on water-induced shape memory response of poly(vinyl alcohol): design concept and 4D printing feasibility.

The use of shape memory polymers exhibiting water-induced shape recovery at body temperature and water solubility was proposed for the development of indwelling devices for intravesical drug delivery. These could be administered via catheter in a suitable temporary shape, retained in the bladder for a programmed period of time by recovery of the original shape and eliminated with urine following dissolution/erosion. Hot melt extrusion and fused deposition modeling 3D printing were employed as the manufacturing techniques, the latter resulting in 4D printing because of the shape modifications undergone by the printed item over time. Pharmaceutical-grade poly(vinyl alcohol) was selected based on its hot-processability, availability in different molecular weights and on preliminary data showing water-induced shape memory behavior. Specimens having various original and temporary geometries as well as compositions, successfully obtained, were characterized by differential scanning calorimetry and dynamic-mechanical thermal analysis as well as for fluid uptake, mass loss, shape recovery and release behavior. The samples exhibited the desired ability to recover the original shape, consistent in kinetics with the relevant thermo-mechanical properties, and concomitant prolonged release of a tracer. Although preliminary in scope, this study indicated the viability of the proposed approach to the design of retentive intravesical delivery systems.

Assessment of hot-processability and performance of ethylcellulose-based materials for injection-molded prolonged-release systems: An investigational approach.

The present work focuses on application of an investigational approach to assess the hot-processability of pharmaceutical-grade polymers with a potential for use in the manufacturing of reservoir drug delivery systems via micromolding, and the performance of resulting molded barriers. An inert thermoplastic polymer, ethylcellulose (EC), widely exploited for preparation of prolonged-release systems, was employed as a model component of the release-controlling barriers. Moldability studies were performed with plasticized EC, as such or in admixture with release modifiers, by the use of disk-shaped specimens ≥ 200 µm in thickness. The disks turned out to be a suitable tool for evaluation of the dimensional stability and diffusional barrier performance of the investigated materials after demolding. The effect of the amount of triethyl citrate, used as a plasticizer, on hot-processability of EC was assessed. The rate of a model drug diffusion across the polymeric barriers was shown to be influenced by the extent of porosity from the incorporated additives. The investigational approach proposed, of simple and rapid execution, holds potential for streamlining the development of prolonged-release systems produced by micromolding in the form of drug reservoirs, with no need for molds and molding processes to be set up on a case-by-case basis.