Determining the Polymer Threshold Amount for Achieving Robust Drug Release from HPMC and HPC Matrix Tablets Containing a High-Dose BCS Class I Model Drug: In Vitro and In Vivo Studies

Abstract

It is challenging to achieve mechanically robust drug-release profiles from hydrophilic matrices containing a high dose of a drug with good solubility. However, a mechanically robust drug release over prolonged period of time can be achieved, especially if the viscosity and amount of the polymer is sufficiently high, above the "threshold values." The goal of this research was to determine the hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC) polymer threshold amount that would enable robust drug release from matrix tablets containing a high dose of levetiracetam as a class I model drug according to the Biopharmaceutical Classification System (BCS). For this purpose, formulations containing HPC or HPMC of similar viscosity range, but in different amounts, were prepared. Based on the dissolution results, two final formulations were selected for additional in vitro and in vivo evaluation to confirm the robustness and to show bioequivalence. Tablets were exposed to various stress conditions in vitro with the use of different mechanically stress-inducing dissolution methods. The in vitro results were compared with in vivo results obtained from fasted and fed bioequivalence studies. Under both conditions, the formulations were bioequivalent and food had a negligible influence on the pharmacokinetic parameters C max and area under the curve (AUC). It was concluded that the drug release from both selected formulations is mechanically robust and that HPC and HPMC polymers with intrinsic viscosities above 9 dL/g and in quantities above 30% enable good mechanical resistance, which ensures bioequivalence. In addition, HPC matrices were found to be more mechanically robust compared to HPMC.

The importance of binder moisture content in Metformin HCL high-dose formulations prepared by moist aqueous granulation (MAG)

“…Uroš et al evaluated the hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) polymer threshold amount for robust drug release from matrix tablets containing high dose levetiracetam (BCS class Ι compounds). The evaluation of the amount of HPC and HPMC achieved a good correlation of in vitro results and in vivo results [11] .…”

3D-Printed Veterinary Dosage Forms—A Comparative Study of Three Semi-Solid Extrusion 3D Printers

“…All ODFs showed a high R 2 for the Korsmeyer–Peppas drug diffusion model and had N values above 0.5, indicating that the release mechanism is non-Fickian diffusion, which indicates that the drug is released from the dosage form by diffusion and swelling, and that the release is time-dependent. The drug usually releases from a HPC matrix by swelling of the HPC, leading to erosion and diffusion from the gel layer [ 46 ]. The drug release of the DL films in water showed good correlation (R 2 < 0.99) for all the models except the zero order.…”

3D-Printed Veterinary Dosage Forms – A Comparative Study of Three Semi-Solid Extrusion Printers

“…All ODFs showed a high R 2 for the Korsmeyer-Peppas drug diffusion model and had N value above 0.5 indicating that the release mechanism is non-Fickian diffusion which indicates that the drug is released from the dosage form by diffusion and swelling and that the release is time-dependent. The drug releases usually from an HPC matrix by swelling of the HPC leading to erosion and diffusion from the gel layer [44]. The drug release of the DL films in water showed good correlation (R 2 <0.99) for all the models except the zero order.…”