Stabilization of fenofibrate in low molecular weight hydroxypropylcellulose matrices produced by hot-melt extrusion

Abstract

The objective of this study was to improve the dissolution rate and to enhance the stability of a poorly water-soluble and low glass-trasition temperature (T(g)) model drug, fenofibrate, in low molecular weight grades of hydroxypropylcellulose matrices produced by hot-melt extrusion (HME). Percent drug loading had a significant effect on the extrudability of the formulations. Dissolution rate of fenofibrate from melt extruded pellets was faster than that of the pure drug (p < 0.05). Incorporation of sugars within the formulation further increased the fenofibrate release rates. Differential scanning calorimetry results revealed that the crystalline drug was converted into an amorphous form during the HME process. Fenofibrate is prone to recrystallization due to its low T(g). Various polymers were evaluated as stabilizing agents among which polyvinylpyrrolidone 17PF and amino methacrylate copolymer exhibited a significant inhibitory effect on fenofibrate recrystallization in the hot-melt extrudates. Subsequently immediate-release fenofibrate tablets were successfully developed and complete drug release was achieved within 5 min. The dissolution profile was comparable to that of a currently marketed formulation. The hot-melt extruded fenofibrate tablets were stable, and exhibited an unchanged drug release profile after 3-month storage at 40°C/75% RH.

Mefenamic acid taste-masked oral disintegrating tablets with enhanced solubility via molecular interaction produced by hot melt extrusion technology

“…However, the disappearance of the MA melting peak in both of the physical mixtures up to 40% drug load and the melt extrudates confirmed the formation of amorphous solid dispersions of MA in Eudragit ® E PO. Additionally, the absence of the melting peak in the thermograms indicates that the drug was completely solubilized in the melt-extruded matrices [27]. …”

Influence of pressurized carbon dioxide on ketoprofen-incorporated hot-melt extruded low molecular weight hydroxypropylcellulose

“…There are many advantages of using HME over the conventional pharmaceutical processing methods, such as it is a relatively fast continuous manufacturing process 7, 8 and it can convert an active pharmaceutical ingredients (API) into its amorphous state 9 . Moreover, another important advantage of HME is that no solvent is required, so it is considered a “green method” to enhance the solubility and oral bioavailability of poorly water soluble drugs 10, 11 .…”

Development of an antifungal denture adhesive film for oral candidiasis utilizing hot melt extrusion technology

“…It is used in the production of a variety of dosage forms including tablets, pellets, and novel drug delivery systems [17–21]. Examples of advantages of this technique over traditional methods include: 1) enhancing solubility (and hence bioavailability) of poorly soluble drugs by molecularly dispersing the drug within the polymer matrix, 2) processing is environmentally friendly since no organic solvents or water are used, 3) it lends itself to a continuous and less labor intensive process, which is amenable to Quality by Design (QbD) and Process Analytical Techniques (PAT), and 4) it is considered as a promising method to manufacture scalable products.…”