The Influence Of Screw Configuration And Other Mechanistic Approaches On The Morphology And Release Of Drugs From Polymeric Matrices Utilizing Hot-Melt Extrusion Technology

Twin-screw extrusion, often referred to as Hot-Melt Extrusion within the pharmaceutical industry, is an efficient, continuous and solvent-free process that has been investigated extensively for its solubility enhancement applications, and, to a lesser degree, for its potential to replace more conventional “batch” technologies. The research contained herein focuses on the latter of these with attention paid to the effects of screw configuration. In this research, the twin-screw extrusion process was utilized to produce taste masked formulations of a BCS I API, which necessitated the prevention of amorphous phase formation. The resulting granules were subsequently incorporated into an immediate release orally disintegrating tablet (ODT) platform. This processing technology was also evaluated as an alternative platform for the production of dry granulations, henceforth referred to as Twin-Screw Dry Granulation (TSDG). This novel processing approach was investigated using Quality by Design (QbD) principles; however, as the QbD paradigm in product oriented, the process was assessed by the successful production of a drug intermediate and, ultimately, an optimized target formulation. The TSDG process was utilized to produce a high drug loaded sustained release solid oral dosage form in which the crystalline lattice was preserved. Moreover, as a fundamental purpose of granulating technologies is the improvement of the flowability of one or more of the granule constituents, the resulting granules were assessed for enhanced flowability when compared to the very poorly flowing API. Finally, the effects of screw configuration on API morphology was evaluated for the effects of system dependence as the observed existing literature focuses on single systems wherein the effects of screw configuration on API morphology are not assessed for their variations from one carrier system to another. Moreover, the effects of screw configuration were evaluated from the standpoint of the preservation of the API crystalline lattice as the observed existing information on screw configuration within the pharmaceutical literature focuses on solubility enhancement via conversion of the API crystalline lattice into either a molecularly dispersed solid solution or an amorphous solid dispersion

Development and evaluation of an oral fast disintegrating anti-allergic film using hot-melt extrusion technology

The main objective of this novel study was to develop chlorpheniramine maleate orally disintegrating films (ODF) using hot-melt extrusion technology and evaluate the characteristics of the formulation using in vitro and in vivo methods. Modified starch with glycerol was used as a polymer matrix for melt extrusion. Sweetening and saliva-simulating agents were incorporated to improve palatability and lower the disintegration time of film formulations. A standard screw configuration was applied, and the last zone of the barrel was opened to discharge water vapors, which helped to manufacture non-sticky, clear, and uniform films. The film formulations demonstrated rapid disintegration times (6–11 s) and more than 95% dissolution in 5 min. In addition, the films had characteristic mechanical properties that were helpful in handling and storage. An animal model was employed to determine the taste masking of melt-extruded films. The lead film formulation was subjected to a human panel for evaluation of extent of taste masking and disintegration

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

The objective of this study was to enhance the solubility as well as to mask the intensely bitter taste of the poorly soluble drug, Mefenamic acid (MA). The taste masking and solubility of the drug was improved by using Eudragit® E PO in different ratios via hot melt extrusion (HME), solid dispersion technology. Differential scanning calorimetry (DSC) studies demonstrated that MA and E PO were completely miscible up to 40% drug loads. Powder X-ray diffraction analysis indicated that MA was converted to its amorphous phase in all of the formulations. Additionally, FT-IR analysis indicated hydrogen bonding between the drug and the carrier up to 25% of drug loading. SEM images indicated aggregation of MA at over 30% of drug loading. Based on the FT-IR, SEM and dissolution results for the extrudates, two optimized formulations (20% and 25% drug loads) were selected to formulate the orally disintegrating tablets (ODTs). ODTs were successfully prepared with excellent friability and rapid disintegration time in addition to having the desired taste-masking effect. All of the extruded formulations and the ODTs were found to be physically and chemically stable over a period of 6 months at 40 °C/75% RH and 12 months at 25 °C/60% RH, respectively