Hot-melt extruded

ExxonMobil Chemical Company, On-line properties analysis of a molten polymer by Raman spectroscopy for control of a mixing device. Inventors D.G. Marrow, D.A. Yahn, and T.R. Veariel. 20 pp. (inch 10 fig.). Appl. 22 Jul 2005. Int. Cl. GOIJ 3/44 GOIN 21/65. US Patent Application Publication 2007/0019190 Al 105. V.S. Tumuluri, M.S. Kemper, I.R. Lewis, S. Prodduturi, S. Majumdar, B.A. Avery and M.A. Repka, Off-line and on-line measurements of drug-loaded hot-melt extruded films using Raman spectroscopy, Int. J. Pharm., 357, 77-84 (2008). 

V.S. Tumuluri, M.S. Kemper, I.R. Lewis, S. Prodduturi, S. Majumdar, B.A. Avery and M. Repka, Off-line and on-hne measnrements of dmg-loaded hot-melt extruded films using Raman spectroscopy, Int. J. Pharm., 357, 77-84 (2008). 

Zhu, Y., et al., Controlled release of a poorly water-soluble drug from hot-melt extrudates containing acrylic polymersPrug. Dev. Ind. Pharm., 32, 569, 2006. 

An early example of Raman mapping by Breitenbach et al. [52] showed that when crystalline ibuprofen is formulated in a hot melt extrudate the API changes to the amorphous form. Ibuprofen is a sparingly water-soluble compound, so this formulation provides a route to better bioavailability via the more soluble amorphous form. Using confocal Raman mapping the form of the API was determined at the time of manufacture and under stress conditions and was used to assess the stability of the amorphous form. These studies also showed that the API was homogeneously distributed throughout the formulation based on the relative band intensities of the amorphous API and a formulation excipient, polyvinylpyrrolidone (PVP). 

Fukuda, M., Peppas, N. A., and McGinity, J. W. (2006), Properties of sustained release hot-melt extruded tablets containing chitosan and xanthan gum, Int. J. Pharm., 310, 90-100. 

The materials used in the production of hot-melt extruded dosage forms must meet the same levels of purity and safety as those used in traditional dosage forms. Most of the compounds used in the production of hot-melt extruded pharmaceuticals have been used in the production of other solid dosage forms such as tablets, pellets, and transdermals. The materials used in hot-melt extruded products must possess some degree of thermal stability in addition to acceptable physical and chemical stability. The thermal stability of each individual compound and the composite mixture should be sufficient to withstand the production process. 

Hot-melt extruded dosage forms are complex mixtures of active medicaments and functional excipients. The functional excipients may be broadly classified as matrix carriers, release modifying agents, bulking agents, and miscellaneous additives. The selection and use of various excipients can impart specific properties to hot-melt extruded pharmaceuticals in a manner similar to those in traditional dosage forms. 

Table 1 Properties of selected carriers used in the design and production of hot-melt extruded dosage forms...

Plasticizers may also be incorporated into hot-melt extruded dosage forms to improve the physical-mechanical properties of the final dosage form. In transdermal films, the addition of a plasticizer to the... 

Table 2 Stability of polyethylene oxide (MW 1,000,000) in hot-melt extruded tablet formulations containing 6wt% chlorpheniramine maleate processed at different temperatures...

Table 3 Stability of plasticizers in hot-melt extruded HPC films processed at 180°C as a function of storage conditions (n — 6)...

Fig. 6 Influence of the granule particle size on the theophylline release properties of the tablets containing hot-melt extruded granules (n = 3). Tablets 20% extruded granules (Formula 3 25% theophylline, 2% PEG, and 73% PVAc), 79.5% Avicel PH200, and 0.5% magnesium stearate ( ) Less than 125 pm (i) 180-212 pm (a) 300 25 pm (O) 500-600 pm. (From Ref. l)...

Fig. 13 Differential scanning calorimetry profiles of hot-melt extruded films containing chlorpheniramine maleate and hydroxypropylcellulose (A) chlorpheniramine maleate (CPM) (B) 10% CPM and 90% HPC (Klucel HF) physical mix and (C) 10% CPM and 90% HPC (Klucel HF) extruded film. (From Ref. )...

Fig. 15 Glass transition temperatures of films containing different levels of Vitamin E TPGS incorporated into two formulations of HPC/PEO hot-melt extruded films n = 4). (From Ref - l)...

A bioadhesive hot-melt extruded film for intraoral drug delivery and the processing thereof has been patented.f Applications of these films may be utilized in transmucosal drug delivery or even transder-mal systems. The films may be produced separately and layered after extrusion, or in some cases, a multilayered system may be extruded in one continuous process. Currently on the market is an extruded film device that is utilized as a denture adhesive. This system includes thermoplastic polymers that have a bioadhesive quality when the film is wetted. Before application and wetting, however, this thin film may be held in one s hand and shaped or cut. This device is again produced by a one-step, continuous process using hot-melt extrusion technology. 

Table 7 Processing conditions for hot-melt extruded films containing a 50 50 ratio of hydroxypropylcellulose to polyethylene oxide with vitamin E TPGS as an additive n — 4)...

Fig. 19 Example of a force-deflection profile obtained from a butt bioadhesion experiment utilizing hot-melt extruded films in vivo using a Chatillon digital force gauge attached to a motorized test stand. (From Ref. l)...

Fig. 20 Force of adhesion of hydroxypropylcellulose hot-melt extruded films containing various polymer additives (12 subjects, n — 6). (From Ref l)...

Table 8 Release of acetaminophen from hot-melt extruded granules and tablets prepared from hot-melt extruded granules containing poly(ethylene glycol) 6000 as a thermal binder in 900ml of 50mM phosphate buffer (pH 5.8) at 37°C and a paddle speed of 50rpm...

Follonier, N. Doelker, E. Cole, E.T. Various ways of modulating the release of diltiazem hydrochloride from hot-melt extruded sustained release pellets prepared using polymeric materials. J. Controlled Release 1995, 36, 243-250. 

Repka, M.A. McGinity, J.W. Physical-mechanical, moisture absorption and bioadhesive properties of hydroxy-propylcellulose hot-melt extruded films. Biomaterials 2000, 21 (14), 1509-1517. 

Zhang, F. McGinity, J.W. Properties of hot-melt extruded theophylline tablets containing poly (vinyl acetate). Drug Dev. Ind. Pharm. 2000, 29 (6), 938-948. 

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