Erodible coatings based on HPMC and cellulase for oral time-controlled release of drugs

Abstract

Oral drug delivery systems for time-controlled release, intended for chronotherapy or colon targeting, are often in the form of coated dosage forms provided with swellable/soluble hydrophilic polymer coatings. The latter are responsible for programmable lag phases prior to release, due to their progressive hydration in the biological fluids. When based on high-viscosity polymers and/or manufactured by press-coating, the performance of functional hydroxypropyl methylcellulose (HPMC) layers was not fully satisfactory. Particularly, it encompassed an initial phase of slow release because of outward diffusion of the drug through a persistent gel barrier surrounding the core. To promote erosion of such a barrier, the use of a cellulolytic product (Sternzym  C13030) was here explored. For this purpose, the dry mass loss behavior of tableted matrices based on various HPMC grades, containing increasing percentages of Sternzym ® C13030, was preliminarily \studied, highlighting a clear and concentration-dependent effect of the enzyme especially with high-viscosity polymers. Subsequently, Sternzym  C13030-containing systems, wherein the cellulolytic product was either incorporated into a high-viscosity HPMC coating or formed a separate underlying layer, were manufactured. Evaluated for release, such systems gave rise to more reproducible profiles, with shortened lag phases and reduced diffusional release, as compared to the reference formulation devoid of enzyme.

Oral colon delivery platform based on a novel combination approach: Design concept and preliminary evaluation

“…The outer Eudragit ® S/Amylo N460 layer was applied onto tablets coated with low-viscosity HPMC or injection-molded HPC capsules. Both the HPMC-coated tablets and the injection-molded HPC capsules were designed to provide time-controlled release with a pre-programmed lag phase [22,23,33,34]. The Eudragit ®.…”

Cellulase as an “active” excipient in prolonged-release HPMC matrices: A novel strategy towards zero-order release kinetics

“…At scheduled time points during the test, 50 ml of fluid was withdrawn, replaced with fresh medium, and dried at 80 °C to constant weight (Foppoli et al, 2020b).…”

“…In the field of pharmaceutical formulation, the effect of cellulase on the release kinetics of a time-controlled oral delivery system (Chronotopic™) was recently investigated, following pioneering attempts to exploit glycosidases, namely pectinase, in the design of a capsular device (Krögel and Bodmeier, 1999;Bussemer et al, 2001;Foppoli et al, 2020b; ). The Chronotopic™ system was based on a functional hydroxypropyl methylcellulose (HPMC) layer intended to defer the onset of release through progressive dissolution/erosion undergone in contact with aqueous fluids.…”

Orally administered niclosamide-based organic/inorganic hybrid suppresses SARS-CoV-2 infection

“…In addition, MgO itself could be used as an adjuvant medicine for COVID-19 therapy as evidenced by several reported studies [23]. The NIC-MgO oral formulation was finally coated with pharmaceutically inert, FDA approved excipient, hydroxy propyl methyl cellulose (HPMC) [24][25][26][27][28], to make the final product as NIC-MgO-HPMC which is expected to have better pharmacokinetic (PK) effects to sustain the NIC release for improved therapeutic effects against SARS-CoV-2 pre-clinical and clinical studies . Previously, we could also understand that repurposed NIC formulation with montmorillonite (MMT) [29], hydrotalcite [22], porous silicas and geopolymer [30] enhanced the PK performance of NIC.…”