Impact of Mixing on Content Uniformity of Thin Polymer Films Containing Drug Micro-Doses

Abstract

The impact of mixer type and critical process parameters (CPPs) on critical quality attributes (CQAs), including the drug content uniformity (CU) of slurry-cast polymer films loaded with micro-sized poorly water-soluble drugs were investigated. Previously untested hypothesis was that the best mixer at suitable CPPs promotes uniform drug dispersion within film precursors leading to acceptable dried-film CU at low, ~0.6 wt% drug concentrations. Taguchi design was utilized to select the best of three mixers; low-shear impeller, high-shear planetary, and high-intensity vibrational, for dried-film drug concentration of ~23 wt%. As-received fenofibrate, a model poorly water-soluble drug (~6 µm) was directly mixed with the hydroxypropyl methylcellulose (HPMC) and glycerin aqueous solution. Impeller and planetary mixers yielded desirable film relative standard deviation (RSD), while vibrational mixer could not. For the lowest dried-film drug concentration of ~0.6 wt%, only planetary mixer yielded RSD <6%. The precursor drug homogeneity was a sufficient but not a necessary condition for achieving dried-film RSD <6%. Thus, proper selection of mixer and its CPPs assured desirable film CQAs. However, minor drug particle aggregation was identified via re-dispersion testing which also led to incomplete drug release.

Specialised Coating Processes Finding Pharmaceutical Applicability

“…It is a sophisticated bench top mixer finds suitability for particulate substrate coating following DCM 32,33 . Sophistication herein is, the mixing operation is based on resonant acoustic technology [32][33][34][35][36] . Employment of said technology creates a low frequency, high intensity shear field 34,35 .…”

“…Sophistication herein is, the mixing operation is based on resonant acoustic technology [32][33][34][35][36] . Employment of said technology creates a low frequency, high intensity shear field 34,35 . This is resulting intense vibration that helps in thorough & uniform blending of powdery material within very short time span 35.…”

Thermo-Mechanical Dry Coating as Dry Coating Process is for Pharmaceuticals

“…Here mixing operation is founded on resonant acoustic technology 47 . Said technology creates a low frequency and high intensity shear field 48 . Generated shear field helps in uniform & thorough mixing of material within very short time 46 .…”

“…Said vibrations are to create high shearing zones, within the mixing vessel of the device 47 . Said state along with high energy creates a virtually fluidised state for powder of FiUlFiPs, comprising GPs and HPs 48 . Due to fluidisation process submicron sized GPs collide with HPs.…”

“…Thereby resulting is in dry-coated HPs with uniform coating layer 46 . To control intensity of vibration and mixing time there is external digital control system 48 . These may be coated with polyurethane 1 .…”