Establishment of a Molding Procedure to Facilitate Formulation Development for Co-extrudates

Abstract

Co-extrusion offers a number of advantages over conventional manufacturing techniques. However, the setup of a co-extrusion line is cost- and time-intense and formulation development is challenging. This work introduces a novel procedure to test the applicability of a co-extruded reservoir-type system at an early product development stage. We propose vacuum compression molding (VCM), a fast procedure that requires only small material amounts, for the manufacturing of cylindrical reservoir-type system. To this end, the commercially available co-extruded product NuvaRing and variations thereof were used as test systems. All VCM systems showed a homogeneous skin thickness that adhered well to the core, thereby providing a precise core/skin interface. As drug release is a key criterion for pharmaceutical products, a modified in vitro dissolution method was set up to test the VCM systems. The drug release from the VCM systems was in the same order of magnitude as the corresponding co-extruded strands and followed the same release kinetics. Moreover, the VCM systems were capable of indicating the relative effect of formulation-related modifications on drug release. Overall, this shows that this system is a powerful tool that facilitates formulation tailoring and co-extrusion process setup at the earliest stage.

Controlled-Release from High-Loaded Reservoir-Type Systems—A Case Study of Ethylene-Vinyl Acetate and Progesterone

“…For IVRs, the required P4 target release rate is 5 and 10 mg/day [15,16]. In this study, small-scale VCM systems were used, which predict the drug release from the corresponding IVRs [17,18]. The VCM systems consist of a cylindrical core of 10 mm diameter and two EVA membranes attached to the flat circular surfaces of the core [17].…”

“…In this study, small-scale VCM systems were used, which predict the drug release from the corresponding IVRs [17,18]. The VCM systems consist of a cylindrical core of 10 mm diameter and two EVA membranes attached to the flat circular surfaces of the core [17]. Considering the different diffusional areas of a VCM system (i.e., 1.57 cm 2 ) and an IVR of NuvaRing ® dimensions (i.e., 19.35 cm 2 ), the target P4 release from the VCM systems is 400 and 800 µg/day to achieve the 5 and 10 mg/day release from the corresponding IVRs.…”

“…The core and the membranes were produced separately via the VCM technology and finally combined, to form the VCM systems of 10 mm diameter and 4 mm height Formulation details are given in Table 1. Details of the preparation method can be found elsewhere [17]. To prepare the membranes, 6.7-21 mg of EVA9, EVA18 or EVA28 -depending on the target membrane thickness -were processed at 140 • C (EVA9) and 110 • C (EVA18, EVA28).…”

“…Therefore, in our study, we defined both target release rates. In an attempt to save material and time, we applied and further developed small-scale systems that were recently shown to predict the performance of IVRs by our group [17,18]. In a first step, we rationally designed reservoir systems based on the physicochemical properties of the selected drug and the polymers.…”

Determining Thermal Conductivity of Small Molecule Amorphous Drugs with Modulated Differential Scanning Calorimetry and Vacuum Molding Sample Preparation

“…The method is based on combining vacuum molding sample preparation with regular modulated differential scanning calorimetry (mDSC), utilizing a previously reported method [9]. Sample preparation tools using vacuum compression molding are increasingly becoming part of the standard analytical equipment park within pharmaceutical research and development [10][11][12] and DSC is a regular part of sample characterization, in particular for amorphous compounds. Several methods and a few application notes, published by thermal equipment manufacturers, using DSC to measure thermal conductivity are described in the literature [9,[13][14][15][16][17].…”