Pharmaceutical Applications of Hot-Melt Extrusion: Part I

Figures & data

FIGURE 1. The number of hot-melt extrusion patents issued for pharmaceutical applications from 1983 to 2006.

FIGURE 2. The number and percentage of hot-melt extrusion patents issued by country since 1983 for pharmaceutical applications.

FIGURE 3. Twin screw prism USALAB digital 16 mm extruder (top), twin screw extruder (Courtesy of American Leistritz Co., Somerville, NJ) (bottom).

FIGURE 4. Twin screw design examples: intermeshing co-rotating twin-screw (top), and intermeshing counter-rotating twin-screw (Burns et al.). (Courtesy of American Leistritz Co., Somerville, NJ) (bottom).

FIGURE 5. Diagram of an extruder screw (repka et al., 2002a). 1) the channel depth is the distance from the screw roots to the inner barrel surface; 2) the flight clearance is the distance between the screw flight and the inner barrel surface; 3) the channel width is the distance between two neighboring flights; 4) the helix angle is the angle between the flight and the direction perpendicular to the screw axis.

FIGURE 6. Schematic diagram of a single screw extruder.

FIGURE 7. Illustration of a pelletizer used to chop rod shaped extrudates into pellets or granules. (Courtesy of Randcastle extrusion systems Inc., NJ).

FIGURE 8. Illustration of a hot-melt extrusion film assembly (top) with chill roller flake unit (bottom). (Courtesy of Thermo Electron Corporation, MA).

TABLE 1. Carriers Used to Prepare Hot-melt Extruded Dosage Forms

Chemical Name	Trade Name	Tg (°C)	Tm (°C)	References
Ammonio methacrylate copolymer	Eudragit® RS/RL	64	–	(Follonier, N. et al., 1994; Kidokoro et al., 2001; Zhu et al., 2002)
Poly(dimethylaminoethylmethacrylate-co-methacrylic esters)	Eudragit® E	50	–	(Aitken-Nichol et al., 1996; Repka et al., 2000b; Repka et al., 2001a)
Poly(methyl acrylate-co-methyl methacrylate-co-methacrylic acid)7:3:1	Eudragit® 4135F	48	–	(Young et al., 2002)
Poly(methacrylic acid-co-methyl methacrylate) 1:2	Eudragit® S	160	–	(Follonier et al., 1995)
Hydroxypropyl cellulose	Klucel®	130	–	(Repka et al., 1999a; Repka et al., 2000a; Repka et al., 2000b; Repka et al., 2001a; Repka et al., 2001b; Repka et al., 2002d; Sato et al., 1997)
Ethyl cellulose	Ethocel®	133	–	(Crowley et al., 2004b; De Brabander et al., 2002; Follonier, N. et al., 1994; Follonier et al., 1995)
Cellulose acetate butyrate	CAB 381-0.5	125	157	(Follonier, N. et al., 1994; Follonier et al., 1995; Sprockel et al., 1997)
Cellulose Acetate Phthalate	–	165	192	(Follonier et al., 1995; Rippie et al., 1969)
Poly(ethylene oxide)	Polyox® WSR	−67	65–80	(Crowley et al., 2002; McGinity et al., 1997; Repka et al., 1999a; Repka et al., 2000a; Repka et al., 2002b; Zhang, 1999)
Poly(ethylene glycol)	Carbowax®	–20	37–63	(Cuff et al., 1998; Forster et al., 2001c; Hamaura et al., 1999; Hulsmann, S. et al., 2000; Koleng et al., 1997; Perissutti et al., 2002; Repka et al., 2001c)
Poly(vinyl pyrrolidone)	Kollidon®	168	–	(Follonier et al., 1995; Forster et al., 2001a; Forster et al., 2001c; Hamaura et al., 1999; Hulsmann et al., 2001; Keleb et al., 2001)
Poly(vinyl acetate)	Sentry® plus	35–40	–	(Sprockel et al., 1997; Zhang et al., 2000)
Hydroxypropyl Methylcellulose Phthalate	–	137	150	(Follonier et al., 1995; Nakamichi et al., 2002)
Polyvinylpyrrolidone-co-vinyl acetate	Kollidon® VA64	–	–	(Forster et al., 2001c; Hulsmann, S. et al., 2000)
Hydroxypropyl Methylcellulose	Methocel®	175	–	(Liu et al., 2001)
Hydroxypropyl Methylcellulose Acetate Succinate	Aqoat-AS®	–	–	(Nakamichi et al., 2001)
Poly(lactide-co-glycolide)	PLGA	–	–	(Bhardwaj et al., 1997; Bhardwaj et al., 1998)
Polyvinyl Alcohol	Elvanol®	–	–	(Follonier et al., 1995)
Chitosan Lactate	Sea-Cure®	–	–	(Follonier et al., 1995)
Pectin	Obipektin®	–	–	(Follonier et al., 1995)
Carbomer	Carbopol® 974P	–	–	(Repka et al., 2000b; Repka et al., 2001a)
Polycarbophil	Noveon® AA-1	–	–	(Repka et al., 2000b; Repka et al., 2001a)
Poly(ethylene-co-vinyl acetate)	Elvax® 40W	–36	45	(Follonier, N. et al., 1994; Van Laarhoven, J. A. H. et al., 2002; Van Laarhoven, J.A.H. et al., 2002)
Polyethylene	–	–125	140	(Aitken-Nichol et al., 1996; Sprockel et al., 1997)
Poly(vinyl acetate-co-methacrylic acid)	CIBA-I	–	84–145	(El-Egakey et al., 1971)
Epoxy resin containing secondary amine	CIBA HI	80–100	–	(El-Egakey et al., 1971)
Polycaprolactone	–	–	–	(Sprockel et al., 1997)
Carnauba Wax	–	–	82–85	(Miyagawa et al., 1996; Miyagawa et al., 1999; Sato et al., 1997)
Ethylene-vinyl acetate copolymer	Evatane®	–	–	(Ringrose et al., 1999)
Glyceryl Palmitostearate	Precirol® ATO 5	–	52–55	(Liu et al., 2001)
Hydrogenated Castor & Soybean Oil	Sterotex® K	–	–	(Liu et al., 2001)
Microcrystalline Wax	Lunacera®Paracera®	–	–	(De Brabander et al., 2000; Zhou et al., 1996)
Corn Starch	–	–	–	(Henrist, D. et al., 1999; Henrist, D. et al., 1999a; Henrist, D. et al., 1999b)
Maltodextrin	–	–	–	(De Brabander et al., 2000)
Pregelatinized Starch	–	–	–	(De Brabander et al., 2000)
Isomalt	Palatinit®	–	145–150	(Ndindayino et al., 2002b; Ndindayino et al., 2002c)
Potato Starch	–	–	–	(Stepto, 1997; Stepto, 2000)
Citric Acid	–	–	153	(Lindberg et al., 1988; Lindberg et al., 1987)
Sodium Bicarbonate	–	–	–	(Lindberg et al., 1987)
Methacrylic acid copolymer type C	Eudragit® L100-55		104.4	(Young Cr, 2005)
Chitosan	–	203	–	(Fukuda et al., 2006b)
Xanthan gum	–	–	–	(Fukuda et al., 2006b)
Agar	–	–	–	(Lyons. J.G., 2006)
Povidone	Plasdone® S-30	–	–	(Ghebremeskel et al., 2006)
Lactose	–	–	201	(Liu et al., 2001; Perissutti et al., 2002)
Microcrystalline cellulose	Avicel® PH 101	–	–	(Liu et al., 2001)
Dibasic calcium phophate	Emcompress®	–	–	(Liu et al., 2001)

TABLE 2. Common Plasticizers Used in Pharmaceutical Dosage Forms

Type	Examples
Citrate esters	triethyl citrate, tributyl citrate, acetyl triethyl citrate, acetyl tributyl citrate
Fatty acid esters	butyl stearate, glycerol monostearate, stearyl alcohol
Sebacate esters	dibutyl sebacate
Phthalate esters	diethyl phthalate, dibutyl phthalate, dioctyl phosphate
Glycol derivatives	Polyethylene glycol, propylene glycol
Others	triacetin, mineral oil, castor oil
Vitamin E TPGS	D-α-tocopheryl polyethylene glycol 1000 succinate

TABLE 3. Common Processing Aids Used in Hot-melt Extruded Dosage Forms

Chemical Name	Trade Name	Reference(s)
Saccharose monopalmitate	Sucroester	(Hulsmann et al., 2001; Hulsmann, S. et al., 2000)
Glycerolester and PEG esters	Gelucire 44/14	(Hulsmann, S. et al., 2000)
Glyceryl monostearate	Imwitor	(Henrist, D. et al., 1999; Henrist, D. et al., 1999a; Henrist, D. et al., 1999b)
d-α-tocopherol(Vitamin E)	–	(Crowley et al., 2002)
Vitamin E Succinate	–	(Crowley et al., 2002)
Vitamin E TPGS	–	(Crowley et al., 2002; Repka et al., 2000a; Repka et al., 2001a)
Butylated Hydroxy Anisole	–	(Crowley et al., 2002)
Methyl Paraben	–	(Wu, 2003)
Mixture of hydrogenated castor oil and soybean oil	Sterotek® K	(Liu et al., 2001)
Glyceryl palmitostearate	Precirol® ATO 5	(Liu et al., 2001)

TABLE 4. Drug Substances Processed by Hot-melt Extrusion Techniques

Drug	Tm (°C)	Reference(s)
Nifedipine	175	(Forster et al., 2001a, 2001c; Nakamichi et al., 2002)
Indomethacin	162.7	(Forster et al., 2001a, 2001b; Forster et al., 2001c)
Piroxicam	204.9	(Forster et al., 2001b)
Tolbutamide	128.4	(Forster et al., 2001a, 2001b)
Lacidipine	184.8	(Forster et al., 2001a, 2001b, 2001c)
Chlorpheniramine Maleate	135	(Crowley et al., 2002; Fukuda et al., 2006a; Repka et al., 1999a, 2001c; Zhang, 1999; Zhu et al., 2002)
Theophylline	255	(Henrist, D. et al., 1999, 1999a 1999b; Sprockel et al., 1997; Young Cr, 2005; Young et al., 2002; Zhang et al., 2000)
17β-estradiol hemihydrate	–	(Hulsmann, S. et al., 2000; Hulsmann et al., 2001)
Oxprenolol hydrochloride	108	(Follonier, N. et al., 1994)
Fenoprofen calcium	–	(Cuff et al., 1998)
Lidocaine	68.5	(Aitken-Nichol et al., 1996; Repka et al., 2005)
Hydrocortisone	220	(Repka et al., 1999a)
Phenylpropanolamine Hydrochloride	192	(Liu et al., 2001)
Hydrochlorothiazide	274	(Keleb et al., 2001; Ndindayino et al., 2002b, 2002c)
Carbamazepine	192	(Perissutti et al., 2002)
Ibuprofen	76	(De Brabander et al., 2002, 2000; Kidokoro et al., 2001)
Melanotan-1	–	(Bhardwaj et al., 1997, 1998)
Diclofenac Sodium	284	(Lyons. J.G., 2006; Sato et al., 1997)
Acetaminophen	170	(Ndindayino et al., 2002a)
Nicardipine Hydrochloride	180	(Nakamichi et al., 2001)
Etonogestrel	200	(Van Laarhoven, J. A. H. et al., 2002; Van Laarhoven, J.A.H. et al., 2002)
Ethinyl estradiol	144	(Van Laarhoven, J.A.H. et al., 2002)
Acetylsalicylic Acid	135	(Stepto, 1997; Stepto, 2000)
Diltiazem Hydrochloride	210	(Follonier, N. et al., 1994; Zhu Y, 2006)
5-Aminosalicylic acid	280	(L. Diane Bruce, 2005)
Itraconazole	166	(Miller. D.A, 2006)
Ketoconazole	148–152	(Mididoddi et al., 2006)
Guaifenesin	78.5	(Crowley et al., 2004a)
Ketoprofen	94	(Crowley et al., 2004a)

TABLE 5. Common Methods Used for the Characterization of Hot-melt Extrudates

Thermoanalytical Methods	Differential Scanning Calorimetry
	Thermogravimetric Analysis
	Hot Stage Microscopy
	Microthermal Analysis
Dissolution Testing
X-Ray Diffraction	Wide Angle X-Ray Diffraction
Spectroscopic Methods	IR
Microscopic Methods	Polarized Light Microscopy
	Scanning Electron Microscopy
	Transmission Electron Microscopy
	Atomic Force Microscopy
Nuclear Magnetic Resonance	Magic Angle Spinning Techniques
	Cross-Polarization Techniques
Mechanical Analysis	Tensile Strength
	Elongation
	Young's Modulus

Follonier N., Doelker E., Cole E. T. Evaluation of hot-melt extrusion as a new technique for the production of polymer-based pellets for sustained release capsules containing high loadings of freely soluble drugs. Drug Dev. Ind. Pharm. 1994; 20(8)1323–1339

 Web of Science ®Google Scholar

Kidokoro M., Shah N. H., Malick A. W., Infeld M. H., McGinity J. W. Properties of tablets containing granulations of ibuprofen and an acrylic copolymer prepared by thermal processes. Pharmaceut. Dev. Tech. 2001; 6(2)263–275

 PubMed Web of Science ®Google Scholar

Zhu Y. C., Shah N. H., Malick A. W., Infeld M. H., McGinity J. W. Solid-state plasticization of an acrylic polymer with chlorpheniramine maleate and triethyl citrate. Int. J. Pharm. 2002; 241(2)301–310

 PubMed Web of Science ®Google Scholar

Aitken-Nichol C., Zhang F., McGinity J. W. Hot melt extrusion of acrylic films. Pharm. Res. 1996; 13(5)804–808

 PubMed Web of Science ®Google Scholar

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

 PubMed Web of Science ®Google Scholar

Repka M. A., McGinity J. W. Bioadhesive properties of hydroxypropylcellulose topical films produced by hot-melt extrusion. J. Contr. Release 2001a; 70(3)341–351

 PubMed Web of Science ®Google Scholar

Young C. R., Koleng J. J., McGinity J. W. Production of spherical pellets by a hot-melt extrusion and spheronization process. Int. J. Pharm. 2002; 242: 87–92

 PubMed Web of Science ®Google Scholar

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. Contr. Release 1995; 36(3)243–250

 Web of Science ®Google Scholar

Repka M. A., Gerding T. G., Repka S. L., McGinity J. W. Influence of plasticizers and drugs on the physical-mechanical properties of hydroxypropylcellulose films prepared by hot-melt extrusion. Drug Dev. Ind. Pharm. 1999a; 25(5)625–633

 PubMed Web of Science ®Google Scholar

Repka M. A., McGinity J. W. Influence of vitamin E TPGS on the properties of hydrophilic films produced by hot-melt extrusion. Int. J. Pharm. 2000a; 202(1–2)63–70

 PubMed Web of Science ®Google Scholar

Repka M. A., McGinity J. W. Influence of chlorpheniramine maleate on topical films produced by hot-melt extrusion. Pharmaceut. Dev. Tech. 2001b; 6(3)295–302

 Web of Science ®Google Scholar

Repka M. A., Repka S. L., McGinity J. W., United States Patent No. 6,375,963 B1, 2002d

 Google Scholar

Sato H., Miyagawa Y. Dissolution mechanism of diclofenac sodium wax matrix granules. J. Pharmaceut. Sci. 1997; 86(8)929–934

 PubMed Web of Science ®Google Scholar

Crowley M. M., Schroeder B., Fredersdorf A., Obara S., Talarico M., Kucera S., et al. Physicochemical properties and mechanism of drug release from ethyl cellulose matrix tablets prepared by direct compression and hot-melt extrusion. Int. J. Pharm. 2004b; 271(1–2)77–84

 PubMed Web of Science ®Google Scholar

De Brabander C., Van Den Mooter G., Vervaet C., Remon J. P. Characterization of ibuprofen as a nontraditional plasticizer of ethyl cellulose. J. Pharm. Sci. 2002; 91(7)1678–1685

 PubMed Web of Science ®Google Scholar

Sprockel O. L., Sen M., Shivanand P., Prapaitrakul W. A melt extrusion process for manufacturing matrix drug delivery systems. Int. J. Pharm. 1997; 155(2)191–199

 Web of Science ®Google Scholar

Rippie E. G., Johnson J. R. Regulation of dissolution rate by pellet geometry. J. Pharmaceut. Sci. 1969; 58(4)428–431

 PubMed Web of Science ®Google Scholar

Crowley M. M., Zhang F., Koleng J. J., McGinity J. W. Stability of polyethylene oxide in matrix tablets prepared by hot-melt extrusion. Biomaterials 2002; 23(21)4241–4248

 PubMed Web of Science ®Google Scholar

McGinity J., Zhang F., World Patent No. 9749384, 1997

 Google Scholar

Repka M. A., O'haver J., See C. H., Gutta K., Munjal M. Nail morphology studies as assessments for onychomycosis treatment modalities. Int. J. Pharm. 2002b; 245: 25–36

 PubMed Web of Science ®Google Scholar

Zhang F. Hot-melt extrusion as a novel technology to prepare sustained-release dosage forms. Unpublished Dissertation, The University Of Texas At Austin, Austin 1999

 Google Scholar

Cuff G., Raouf F. A preliminary evaluation of injection molding as a technology to produce tablets. Pharmaceut. Tech. 1998; 22: 96–106

 Google Scholar

Forster A., Hempenstall J., Tucker I., Rades T. Selection of excipients for melt extrusion with two poorly water-soluble drugs by solubility parameter calculation and thermal analysis. Int. J. Pharm. 2001c; 226: 147–161

 PubMed Web of Science ®Google Scholar

Hamaura T., Newton J. M. Interaction between water and poly(vinylpyrrolidone) containing polyethylene glycol. J. Pharm. Sci. 1999; 88(11)1228–1233

 PubMed Web of Science ®Google Scholar

Hulsmann, S., & Backensfeld, T. (2000). World 0057853.

 Google Scholar

Koleng J. J., McGinity J. W. Preparation and evaluation of rapid-release granules using a novel hot-melt extrusion technique. Paper Presented At The 16th Pharmaceutical Technology Conference, Athens, 1997

 Google Scholar

Perissutti B., Newton J. M., Podczeck F., Rubessa F. Preparation of extruded carbamazepine and PEG 4000 as a potential rapid release dosage form. Eur. J. Pharm. Biopharm. 2002; 53(1)125–132

 PubMed Web of Science ®Google Scholar

Repka M. A., McGinity J. W. Influence of chlorpheniramine maleate on topical hydroxypropylcellulose films produced by hot-melt extrusion. Pharmaceut. Dev. Tech. 2001c; 6(3)297–304

 PubMed Web of Science ®Google Scholar

Forster A., Hempenstall J., Rades T. Characterization of glass solutions of poorly water-soluble drugs produced by melt extrusion with hydrophilic amorphous polymers. J. Pharm. Pharmacol. 2001a; 53(3)303–315

 PubMed Web of Science ®Google Scholar

Hulsmann S., Backensfeld T., Bodmeier R. Stability of extruded 17 ss-estradiol solid dispersions. Pharm. Dev. Technol 2001; 6(2)223–229

 PubMed Web of Science ®Google Scholar

Keleb E. I., Vermeire A., Vervaet C., Remon J. P. Cold extrusion as a continuous single-step granulation and tabletting process. Eur. J. Pharm. Biopharm. 2001; 52(3)359–368

 PubMed Web of Science ®Google Scholar

Zhang F., McGinity J. W. Properties of hot-melt extruded theophylline tablets containing poly(vinyl acetate). Drug Dev. Ind. Pharm. 2000; 26(9)931–942

 PubMed Web of Science ®Google Scholar

Nakamichi K., Nakano T., Yasuura H., Izumi S., Kawashima Y. The role of kneading paddle and the effects of screw revolution speed and water content on the preparation of solid dispersions using a twin-screw extruder. Int. J. Pharm. 2002; 241: 203–211

 PubMed Web of Science ®Google Scholar

Hulsmann S., Backensfeld T., Keitel S., Bodmeier R. Melt extrusion—an alternative method for enhancing the dissolution rate of 17-estradiol hemihydrate. Eur. J. Pharm. Biopharm. 2000; 49: 237–242

 PubMed Web of Science ®Google Scholar

Liu J., Zhang F., McGinity J. W. Properties of lipophilic matrix tablets containing phenylpropanolamine hydrochloride prepared by hot-melt extrusion. Eur. J. Pharm. Biopharm. 2001; 52: 181–190

 PubMed Web of Science ®Google Scholar

Nakamichi K., Yasuura H., Fukui H., Oka M., Izumi S. Evaluation of a floating dosage form of nicardipine hydrochloride and hydroxypropylmethylcellulose acetate succinate prepared using a twin-screw extruder. Int. J. Pharm. 2001; 218(1–2)103–112

 PubMed Web of Science ®Google Scholar

Bhardwaj R., Blanchard J. In vitro evaluation of poly(D, L-lactide-co-glycolide) polymer-based implants containing the alpha-melanocyte stimulating hormone analog, melanotan-I. J. Control. Release 1997; 45(1)49–55

 Web of Science ®Google Scholar

Bhardwaj R., Blanchard J. In vitro characterization and in vivo release profile of a poly(D, L-lactide-co-glycolide)-based implant delivery system for the alpha-msh analog, melanotan-I. Int. J. Pharm. 1998; 170(1)109–117

 Web of Science ®Google Scholar

Van Laarhoven J. A. H., Kruft M. A. B., Vromans H. Effect of supersaturation and crystallization phenomena on the release properties of a controlled release device based on eva copolymer. J. Control. Release 2002; 82(2–3)309–317

 PubMed Web of Science ®Google Scholar

Van Laarhoven J. A. H., Kruft M. A. B., Vromans H. In vitro release properties of etonogestrel and ethinyl estradiol from a contraceptive vaginal ring. Int. J. Pharm. 2002; 232(1–2)163–173

 PubMed Web of Science ®Google Scholar

El-Egakey M. A., Soliva M., Speiser P. Hot extruded dosage forms Part I: Technology and dissolution kinetics of polymeric matrices. Pharm. Acta Helv. 1971; 46: 31–52

 PubMedGoogle Scholar

Miyagawa Y., Okabe T., Yamaguchi Y., Al E. Controlled release of diclofenac sodium from wax matrix granule. Int. J. Pharma. 1996; 138(2)215–224

 Web of Science ®Google Scholar

Miyagawa Y., Sato H., Okabe T., Nishiyama T., Miyajima M. A., Sunada H. In vivo performance of wax matrix granules prepared by a twin- screw compounding extruder. Drug Dev. Ind. Pharm. 1999; 25(4)429–435

 PubMed Web of Science ®Google Scholar

Ringrose B. J., Kronfli E. Feasibility study on the melt processing of radiation-grafted ethylene-vinyl acetate copolymer resins. Adv. Polym. Technol. 1999; 18(4)343–350

 Web of Science ®Google Scholar

De Brabander C., Vervaet C., Fiermans L., Remon J. P. Matrix mini-tablets based on starch/microcrystalline wax mixtures. Int. J. Pharm. 2000; 199(2)195–203

 PubMed Web of Science ®Google Scholar

Zhou F., Vervaet C., Remon J. P. Matrix pellets based on the combination of waxes, starches and maltodextrins. Int. J. Pharm. 1996; 133(1–2)155–160

 Web of Science ®Google Scholar

Henrist D., Lefebvre R. A., Remon J. P. Bioavailability of starch based hot stage extrusion formulations. Int. J. Pharm. 1999; 187(2)185–191

 PubMedGoogle Scholar

Henrist D., Remon J. P. Influence of the formulation composition on the in vitro characteristics of hot stage extrudates. Int. J. Pharm 1999a; 188(1)111–119

 PubMedGoogle Scholar

Henrist D., Remon J. P. Influence of the process parameters on the characteristics of starch based hot stage extrudates. Int. J. Pharm. 1999b; 189(1)7–17

 PubMedGoogle Scholar

Ndindayino F., Vervaet C., Van Den Mooter G., Remon J. Bioavailability of hydrochlorothiazide from isomalt-based moulded tablets. Int. J. Pharm. 2002b; 246(1–2)199–202

 PubMed Web of Science ®Google Scholar

Ndindayino F., Vervaet C., Van Den Mooter G., Remon J. P. Direct compression and moulding properties of co-extruded isomalt/drug mixtures. Int. J. Pharm. 2002c; 235(1–2)159–168

 PubMed Web of Science ®Google Scholar

Stepto R. F. T. Thermoplastic starch and drug delivery capsules. Polym. Int. 1997; 43(2)155–158

 Web of Science ®Google Scholar

Stepto R. F. T. Thermoplastic Starch. Paper Presented At The Macromol. Symp. 2000

 Google Scholar

Lindberg N. O., Tufvesson C., Holm P., Olbjer L. Extrusion of an effervescent granulation with a twin screw extruder, Baker Perkins Mpf 50 D. influence on intragranular porosity and liquid saturation. Drug Dev. Ind. Pharm. 1988; 14(13)1791–1798

 Web of Science ®Google Scholar

Lindberg N. O., Tufvesson C., Olbjer L. Extrusion of an effervescent granulation with a twin screw extruder, Baker Perkins Mpf 50 D. Drug Dev. Ind. Pharm. 1987; 13: 1891–1913

 Web of Science ®Google Scholar

Young C. R. D. C., Cerea M., Farrell T., Fegely K. A., Rajabi Siahboomi A., McGinity J. W. Physicochemical characterization and mechanisms of release of theophylline from melt-extruded dosage forms based on a methacrylic acid copolymer. Int. J. Pharm. 2005; 301(1–2)112–120

 PubMed Web of Science ®Google Scholar

Fukuda M., Peppas N. A., McGinity J. W. Properties of sustained release hot-melt extruded tablets containing chitosan and xanthan gum. Int. J. Pharm. 2006b; 31: 90–100

 Web of Science ®Google Scholar

Lyons J. G. D. D. M., Kennedy J. E., Geever L. M., O'sullivan P., Higginbotham C. L. The use of agar as a novel filler for monolithic matrices produced using hot melt extrusion. Eur. J. Of Pharm. And Biopharm 2006; 64(1)75–81

 PubMed Web of Science ®Google Scholar

Ghebremeskel N. A., Vemavarapu C., Lodaya M. Use of surfactants as plasticizers in preparing solid dispersions of poorly soluble API: Stability testing of selected solid dispersions. Pharm. Res 2006; 23(8)1928–1936

 PubMed Web of Science ®Google Scholar

Wu C. M. J. Influence of methyl praben as a solid-state plasticizer on the physicochemical properties of eudragit RS PO hot-melt extrudates. J. Pharm. Biopharm. 2003; 56(1)95–100

 Google Scholar

Forster A., Hempenstall J., Tucker I., Rades T. The potential of small-scale fusion experiments and the gordon-taylor equation to predict the suitability of drug/polymer blends for melt extrusion. Drug Dev. Ind. Pharm. 2001b; 27(6)549–560

 PubMed Web of Science ®Google Scholar

Fukuda M., Peppas N. A., McGinity J. W. Floating hot-melt extruded tablets for gastroretentive controlled drug release system. J. Of Cont. Rel. 2006a; 115(2)121–129

 PubMed Web of Science ®Google Scholar

Repka M. A., Gutta K., Prodduturi S., Munjal M., Stodghill S. P. Characterization of cellulosic hot-melt extruded films containing lidocaine. Eur. J. Pharm. Biopharm. 2005; 59(1)189–196

 PubMed Web of Science ®Google Scholar

Ndindayino F., Henrist D., Kiekens F., Van Den Mooter G., Vervaet C., Remon J. P. Direct compression properties of melt-extruded isomalt. Int. J. Pharm 2002a; 235(1–2)149–157

 PubMedGoogle Scholar

Zhu Y. S. N., Malick A. W., Infeld M. H., McGinity J. W. Controlled release of a poorly water-soluble drug from hot-melt extrudates containing acrylic polymers. Drug Dev. Ind. Pharm. 2006; 32(5)569–583

 PubMed Web of Science ®Google Scholar

Bruce L. D. N. H. S., Malick A. W., Infeld M H., McGinity J. W. Properties of hot-melt extruded tablet formulations for the colonic delivery of 5-aminosalicylic acid. Eur. J. Pharm. Biopharm. 2005; 59(1)85–97

 PubMed Web of Science ®Google Scholar

Miller D. A, M. J. T., Yang W., Williams R. O., McGinity J. W. Hot-melt extrusion for enhanced delivery of drug particles. J. Pharm. Sci. 2006; 96: 361–376

 Web of Science ®Google Scholar

Mididoddi P. K., Prodduturi S., Repka M. A. Influence of tartaric acid on the bioadhesion and mechanical properties of hot-melt extruded hydroxypropyl cellulose films for the human nail. Drug Dev. Ind. Pharm. 2006; 32: 1059–1066

 PubMed Web of Science ®Google Scholar

Crowley M. M., Fredersdorf A., Schroeder B., Ucera S., Prodduturi S., Repka M. A., et al. The influence of guaifenesin and ketoprofen on the properties of hot-melt extruded polyethylene oxide films. Eur. J. Pharm. Sci 2004a; 22(5)409–418

 PubMed Web of Science ®Google Scholar