謝 辞
6. T g 曲線の算出 (Gordon-Taylor equation)
薬物/ポリマーの 2 成分混合系の Tg は Gordon-Taylor 式を用いてそれぞれ単一成分の加重平 均の Tg として算出した。141)
Tgmix= {(w1Tg1)+(Kw2Tg2)}
(w1+Kw2) K = ρρ1Tg1
2Tg2
(11)
w : 分配質量
Tg : ガラス転移点
: 密度
7.
Hot Melt Extrusion による SD 調製Thermo Fisher Scientific K.K. 製 HAAKETM MiniCTW を用いて Hot Melt Extrusion を実施した。
操作条件の詳細は以下の通りである。なお実験は 3 回繰り返した。
第 2 章 操作条件 (Validation Study)
サンプル薬物濃度 : 10% (w/w) サンプル量 : 2.5 g
サンプル調製 : TURBULA® mixer, 5 min 調製温度 : 110, 133 and 156oC スクリュー回転速度 : 50 rpm
Passing / Circulation : Passing 加工時トルク : Record 冷却 : 自然冷却
粉砕加工 : Laboratory micromill
整粒 : 目開き 250 μm
第 3 章 操作条件 (DoE Study)
サンプル薬物濃度 : 10-30% (w/w) サンプル量 : 2.5 g
サンプル調製 : TURBULA® mixer, 5 min 調製温度 : 110, 133 and 156oC スクリュー回転速度 : 20, 60 and 100 rpm Passing / Circulation : Passing
加工時トルク : Record 冷却 : 自然冷却
粉砕加工 : Laboratory micromill 整粒 : 目開き 500 μm
8.
混合実験計画法Stat-Ease 製 Design-Expert® software (version 11.0.2.0) の User-Defined Design mode (Combined Mixture-Process Design) を用いて 36 run の実験計画を策定した (Table 20)。なお計画に際し、混 合成分として 3 因子 (IND、JR-05 およびソルビトール) と連続因子として 2 因子 (加工時温度 およびスクリュー回転数) を、それぞれ以下の検討範囲で計画した。設定条件の詳細を以下に示 す。
混合成分比率 連続因子
IND : 10 - 30% 加工時温度 : 110 - 156oC
JR-05 : 50 - 90% スクリュー回転数 : 20 - 100oC
ソルビトール : 0 - 40%
なお IND および JR-05 の検討水準は、第 2 章の IND の Tm 付近における JR-05 中への溶 解度を考慮したうえで設定した。またソルビトールの検討水準に関しては、過去の報告を参考に 設定した。17) 加工時温度の検討水準は、第 2 章を参考に設定した。なお、実験時の体系的な誤 差を可能な限り低減させるために、全ての実験は Design-Expert® software の指示に従いランダム に実施した。さらに、これらの複数因子と検討水準を現実的に実施可能な実験数で計画するため に、本実験計画には反復実験に関する因子は含めなかった。そのため、各モデルの当てはまりの 良さを示す lack-of-fit に関する情報は得ることはできなかった。その代わり、Table 18 示す検証 試験を別途行うことで、今回の実験で得られた各モデルの予測精度を検証した。
Table 20. Parameters of the Formulation and Process Parameters for the Design of Experiment
Number
Formulation Process
Factor A Factor B Factor C Factor D Factor E
Indomethacin
% (w/w)
JR-05
% (w/w)
Sorbitol
% (w/w)
Temperature (oC)
Screw speed (rpm)
1 10 90 0 156 60
2 30 70 0 133 100
3 30 50 20 156 60
4 20 50 30 133 20
5 20 65 15 133 100
6 30 60 10 110 60
7 10 70 20 110 60
8 20 50 30 156 60
9 30 70 0 110 60
10 10 50 40 133 20
11 20 50 30 133 100
12 20 65 15 133 20
13 30 70 0 133 20
14 10 70 20 156 60
15 20 65 15 156 60
16 20 80 0 156 60
17 10 50 40 133 100
18 20 50 30 110 60
19 10 90 0 133 20
20 30 50 20 110 60
21 20 80 0 133 20
22 30 50 20 133 20
23 30 70 0 156 60
24 30 60 10 133 100
25 10 70 20 133 20
26 10 90 0 133 100
27 20 65 15 110 60
28 10 90 0 110 60
29 10 50 40 110 60
30 30 50 20 133 100
31 30 60 10 133 20
32 20 80 0 110 60
33 30 60 10 156 60
34 20 80 0 133 100
35 10 70 20 133 100
36 10 50 40 156 60
参考文献
1) Kawabata Y., Wada K., Nakatani M., Yamada S., Onoue S., Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: basic approaches and practical applications. Int.
J. Pharm., 420, 1-10 (2011).
2) Fahr A., Liu X., Drug delivery strategies for poorly water-soluble drugs. Expert Opin. Drug Deliv., 4, 403-416 (2007).
3) Hancock B. C., Parks M., What is the true solubility advantage for amorphous pharmaceuticals? Pharm.
Res., 17, 397-404 (2000).
4) Leuner C., Dressman J., Improving drug solubility for oral delivery using solid dispersions. Eur. J.
Pharm. Biopharm., 50, 47-60 (2000).
5) Paudel A., Worku Z. A., Meeus J., Guns S., Van den Mooter G., Manufacturing of solid dispersions of poorly water soluble drugs by spray drying: formulation and process considerations. Int. J. Pharm., 453, 253-284 (2013).
6) ICH, Impurites: Guidline for residual solvent Q3C (R6). International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (2016).
7) el-Egakey M. A., Soliva M., Speiser P., Hot extruded dosage forms. I. technology and dissolution kinetics of polymeric matrices. Pharm. Acta. Helv., 46, 31-52 (1971).
8) Stankovic M., Frijlink H. W., Hinrichs W. L., Polymeric formulations for drug release prepared by hot melt extrusion: application and characterization. Drug Discov. Today, 20, 812-823 (2015).
9) Repka M. A., Battu S. K., Upadhye S. B., Thumma S., Crowley M. M., Zhang F., Martin C., McGinity J.
W., Pharmaceutical applications of hot-melt extrusion: part II. Drug Dev. Ind. Pharm., 33, 1043-1057 (2007).
10) ICH-Q13, 第 6 回医薬品規制調和国際会議 https://www.mhlw.go.jp/stf/houdou/0000212311.html (accessed 18. 06. 15). (2018).
11) 松田嘉弘, わが国における連続生産の現状と課題について. RSMP, 2, 99-103 (2017).
12) Ambike A. A., Mahadik K. R., Paradkar A., Spray-dried amorphous solid dispersions of simvastatin, a low tg drug: in vitro and in vivo evaluations. Pharm. Res., 22, 990-998 (2005).
13) Paidi S. K., Jena S. K., Ahuja B. K., Devasari N., Suresh S., Preparation, in-vitro and in-vivo evaluation of spray-dried ternary solid dispersion of biopharmaceutics classification system class II model drug. J.
Pharm. Pharmacol., 67, 616-629 (2015).
14) Brough C., Miller D. A., Ellenberger D., Lubda D., Williams R. O., 3rd, Use of polyvinyl alcohol as a solubility enhancing polymer for poorly water-soluble drug delivery (part 2). AAPS PharmSciTech, 17, 180-190 (2016).
15) Brough C., Miller D. A., Keen J. M., Kucera S. A., Lubda D., Williams R. O., 3rd, Use of polyvinyl alcohol as a solubility-enhancing polymer for poorly water soluble drug delivery (part 1). AAPS PharmSciTech, 17, 167-179 (2016).
16) Repka M. A., Shah S., Lu J., Maddineni S., Morott J., Patwardhan K., Mohammed N. N., Melt extrusion:
process to product. Expert Opin. Drug Deliv., 9, 105-125 (2012).
17) De Jaeghere W., De Beer T., Van Bocxlaer J., Remon J. P., Vervaet C., Hot-melt extrusion of polyvinyl alcohol for oral immediate release applications. Int. J. Pharm., 492, 1-9 (2015).
18) Wilkinson A. C., Ishida R., Kikuchi M., Sudo K., Morita M., Crisostomo R. V., Yamamoto R., Loh K. M., Nakamura Y., Watanabe M., Nakauchi H., Yamazaki S., Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation. Nature, in press (2019).
19) 河西将利, 川田章太郎, PVA の結合剤への応用 (技術情報). JAPAN VAM & POVAL Co., Ltd., (2015).
20) Koo O. M., Fiske J. D., Yang H., Nikfar F., Thakur A., Scheer B., Adams M. L., Investigation into stability of poly(vinyl alcohol)-based Opadry(R) II films. AAPS PharmSciTech, 12, 746-754 (2011).
21) Orienti I., Treré R., Zecchi V., Hydrogels formed by cross-linked polyvinylalcohol as colon-specific drug delivery systems. Drug Dev. Ind. Pharm., 27, 877-884 (2001).
22) Goyanes A., Wang J., Buanz A., Martinez-Pacheco R., Telford R., Gaisford S., Basit A. W., 3D printing of medicines: engineering novel oral devices with unique design and drug release characteristics. Mol Pharm, 12, 4077-4084 (2015).
23) Win K. Y., Feng S. S., Effects of particle size and surface coating on cellular uptake of polymeric nanoparticles for oral delivery of anticancer drugs. Biomaterials, 26, 2713-2722 (2005).
24) Abdel-Mottaleb M. M., Mortada N. D., El-Shamy A. A., Awad G. A., Physically cross-linked polyvinyl alcohol for the topical delivery of fluconazole. Drug Dev. Ind. Pharm., 35, 311-320 (2009).
25) Shaheen S. M., Yamaura K., Preparation of theophylline hydrogels of atactic poly(vinyl
alcohol)/NaCl/H2O system for drug delivery system. J. Control. Release, 81, 367-377 (2002).
26) Davaran S., Rashidi M. R., Khandaghi R., Hashemi M., Development of a novel prolonged-release nicotine transdermal patch. Pharmacol Res, 51, 233-237 (2005).
27) Thanoo B. C., Sunny M. C., Jayakrishnan A., Controlled release of oral drugs from cross-linked polyvinyl alcohol microspheres. J. Pharm. Pharmacol., 45, 16-20 (1993).
28) Kemala T., Budianto E., Soegiyono B., Preparation and characterization of microspheres based on blend of poly(lactic acid) and poly(ɛ-caprolactone) with poly(vinyl alcohol) as emulsifier. Arab. J. Chem., 5, 103-108 (2012).
29) Sahoo S. K., Panyam J., Prabha S., Labhasetwar V., Residual polyvinyl alcohol associated with poly (D,L-lactide-co-glycolide) nanoparticles affects their physical properties and cellular uptake. J. Control.
Release, 82, 105-114 (2002).
30) Mu L., Feng S. S., A novel controlled release formulation for the anticancer drug paclitaxel (Taxol):
PLGA nanoparticles containing vitamin E TPGS. J. Control. Release, 86, 33-48 (2003).
31) Rowe R. C. S., Paul J; Quinn, Marian E, Handbook of pharmaceutical excipients. Pharmaceutical Press, (2009).
32) Galindo-Rodriguez S., Allemann E., Fessi H., Doelker E., Physicochemical parameters associated with nanoparticle formation in the salting-out, emulsification-diffusion, and nanoprecipitation methods.
Pharm. Res., 21, 1428-1439 (2004).
33) Davies N. M., Farr S. J., Hadgraft J., Kellaway I. W., Evaluation of mucoadhesive polymers in ocular drug delivery. I. Viscous solutions. Pharm. Res., 8, 1039-1043 (1991).
34) McDonald C. C., Kaye S. B., Figueiredo F. C., Macintosh G., Lockett C., A randomised, crossover, multicentre study to compare the performance of 0.1% (w/v) sodium hyaluronate with 1.4% (w/v) polyvinyl alcohol in the alleviation of symptoms associated with dry eye syndrome. Eye (Lond), 16, 601-607 (2002).
35) Winterton L. C., Lally J. M., Sentell K. B., Chapoy L. L., The elution of poly (vinyl alcohol) from a contact lens: the realization of a time release moisturizing agent/artificial tear. J. Biomed. Mater. Res. B Appl. Biomater., 80, 424-432 (2007).
36) Bourges J. L., Bloquel C., Thomas A., Froussart F., Bochot A., Azan F., Gurny R., BenEzra D., Behar-Cohen F., Intraocular implants for extended drug delivery: therapeutic applications. Adv. Drug Deliv. Rev., 58, 1182-1202 (2006).
37) Felice B., Prabhakaran M. P., Zamani M., Rodríguez A. P., Ramakrishna S., Electrosprayed poly(vinyl alcohol) particles: preparation and evaluation of their drug release profile. Polym. Int., 64, 1722-1732 (2015).
38) Silva D. M., Paleco R., Traini D., Sencadas V., Development of ciprofloxacin-loaded poly(vinyl alcohol) dry powder formulations for lung delivery. Int. J. Pharm., 547, 114-121 (2018).
39) Chaouat M., Le Visage C., Baille W. E., Escoubet B., Chaubet F., Mateescu M. A., Letourneur D., A novel cross-linked poly(vinyl alcohol) (PVA) for vascular grafts. Adv. Funct. Mater., 18, 2855-2861 (2008).
40) Vashisth P., Pruthi V., Synthesis and characterization of crosslinked gellan/PVA nanofibers for tissue engineering application. Mater. Sci. Eng. C, 67, 304-312 (2016).
41) Chiou W. L., Riegelman S., Pharmaceutical applications of solid dispersion systems. J. Pharm. Sci., 60, 1281-1302 (1971).
42) Hancock B. C., Zografi G., Characteristics and significance of the amorphous state in pharmaceutical systems. J. Pharm. Sci., 86, 1-12 (1997).
43) Linn M., Collnot E. M., Djuric D., Hempel K., Fabian E., Kolter K., Lehr C. M., Soluplus® as an effective absorption enhancer of poorly soluble drugs in vitro and in vivo. Eur. J. Pharm. Sci., 45, 336-343 (2012).
44) Lipinski C. A., Drug-like properties and the causes of poor solubility and poor permeability. J.
Pharmacol. Toxicol. Methods, 44, 235-249 (2000).
45) Sakurai A., Sakai T., Sako K., Maitani Y., Polymer combination increased both physical stability and oral absorption of solid dispersions containing a low glass transition temperature drug: physicochemical characterization and in vivo study. Chem. Pharm. Bull., 60, 459-464 (2012).
46) Jang D. J., Sim T., Oh E., Formulation and optimization of spray-dried amlodipine solid dispersion for enhanced oral absorption. Drug. Dev. Ind. Pharm., 39, 1133-1141 (2013).
47) Patel B. B., Patel J. K., Chakraborty S., Shukla D., Revealing facts behind spray dried solid dispersion technology used for solubility enhancement. Saudi. Pharm. J., 23, 352-365 (2015).
48) Breitenbach J., Melt extrusion can bring new benefits to HIV therapy. Am. J. Drug Deliv., 4, 61-64 (2006).
49) Sarode A. L., Sandhu H., Shah N., Malick W., Zia H., Hot melt extrusion (HME) for amorphous solid dispersions: Predictive tools for processing and impact of drug-polymer interactions on supersaturation.
Eur. J. Pharm. Sci., 48, 371-384 (2013).
50) Shah S., Maddineni S., Lu J., Repka M. A., Melt extrusion with poorly soluble drugs. Int. J. Pharm., 453, 233-252 (2013).
51) Tachibana T., Nakamura A., A methode for preparing an aqueous colloidal dispersion of organic materials by using water-soluble polymers: Dispersion of -carotene by polyvinylpyrrolidone. A.
Kolloid-Z.u.Z.Polymere 203, 130-133 (1965).
52) Dave R. H., Patel A. D., Donahue E., Patel H. H., To evaluate the effect of addition of an anionic surfactant on solid dispersion using model drug indomethacin. Drug Dev. Ind. Pharm., 38, 930-939 (2012).
53) Gorajana A., Ying C. C., Shuang Y., Fong P., Tan Z., Gupta J., Talekar M., Sharma M., Garg S., Development of solid dispersion systems of dapivirine to enhance its solubility. Curr. Drug. Deliv., 10, 309-316 (2013).
54) Uekama K., Otagiri M., Cyclodextrins in drug carrier systems. Crit. Rev. Ther. Drug Carrier Syst., 3, 1-40 (1987).
55) Policianova O., Brus J., Hruby M., Urbanova M., Zhigunov A., Kredatusova J., Kobera L., Structural Diversity of solid dispersions of acetylsalicylic acid as seen by solid-state NMR. Mol. Pharm., 11, 516-530 (2014).
56) Vasconcelos T., Sarmento B., Costa P., Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov. Today, 12, 1068-1075 (2007).
57) Terebetski J. L., Cummings J. J., Fauty S. E., Michniak-Kohn B., Combined use of crystalline sodium salt and polymeric precipitation inhibitors to improve pharmacokinetic profile of ibuprofen through supersaturation. AAPS PharmSciTech, 15, 1334-1344 (2014).
58) Comer J., Judge S., Matthews D., Towes L., Falcone B., Goodman J., Dearden J., The intrinsic aqueous solubility of indomethacin. ADMET & DMPK, 2, 18-32 (2014).
59) Abu-Diak O. A., Jones D. S., Andrews G. P., An investigation into the dissolution properties of celecoxib melt extrudates: understanding the role of polymer type and concentration in stabilizing supersaturated drug concentrations. Mol. Pharm., 8, 1362-1371 (2011).
60) Baghel S., Cathcart H., O'Reilly N. J., Theoretical and experimental investigation of drug-polymer interaction and miscibility and its impact on drug supersaturation in aqueous medium. Eur. J. Pharm.
Biopharm., 107, 16-31 (2016).
61) Zhao Y., Inbar P., Chokshi H. P., Malick A. W., Choi D. S., Prediction of the thermal phase diagram of amorphous solid dispersions by Flory-Huggins theory. J. Pharm. Sci., 100, 3196-3207 (2011).
62) Lenz E., Jensen K. T., Blaabjerg L. I., Knop K., Grohganz H., Lobmann K., Rades T., Kleinebudde P., Solid-state properties and dissolution behaviour of tablets containing co-amorphous
indomethacin-arginine. Eur. J. Pharm. Biopharm., 96, 44-52 (2015).
63) Maniruzzaman M., Morgan D. J., Mendham A. P., Pang J., Snowden M. J., Douroumis D., Drug-polymer intermolecular interactions in hot-melt extruded solid dispersions. Int. J. Pharm., 443, 199-208 (2013).
64) Prasad D., Chauhan H., Atef E., Role of molecular interactions for synergistic precipitation inhibition of poorly soluble drug in supersaturated drug-polymer-polymer ternary solution. Mol. Pharm., 13, 756-765 (2016).
65) Fujita H., Ooya T., Yui N., Thermally induced localization of cyclodextrins in a polyrotaxane consisting of β-cyclodextrins and poly(ethylene glycol)-poly(propylene glycol) triblock copolymer. Macromolecules, 32, 2534-2541 (1999).
66) Singh T., Kumar A., Aggregation behavior of ionic liquids in aqueous solutions: effect of alkyl chain length, cations, and anions. J. Phys. Chem. B, 111, 7843-7851 (2007).
67) Ueda K., Higashi K., Yamamoto K., Moribe K., Inhibitory effect of hydroxypropyl methylcellulose acetate succinate on drug recrystallization from a supersaturated solution assessed using nuclear magnetic resonance measurements. Mol. Pharm., 10, 3801-3811 (2013).
68) Anwar J., Boateng P. K., Tamaki R., Odedra S., Mode of action and design rules for additives that modulate crystal nucleation. Angew. Chem. Int. Ed. Engl., 48, 1596-1600 (2009).
69) Erdemir D., Lee A. Y., Myerson A. S., Nucleation of crystals from solution: classical and two-step models. Acc. Chem. Res., 42, 621-629 (2009).
70) Ueda K., Higashi K., Yamamoto K., Moribe K., Equilibrium state at supersaturated drug concentration achieved by hydroxypropyl methylcellulose acetate succinate: molecular characterization using 1H NMR technique. Mol. Pharm., 12, 1096-1104 (2015).
71) Nie H., Mo H., Zhang M., Song Y., Fang K., Taylor L. S., Li T., Byrn S. R., Investigating the interaction pattern and structural elements of a drug-polymer complex at the molecular level. Mol. Pharm., 12, 2459-2468 (2015).
72) Murray N. J., Williamson M. P., Lilley T. H., Haslam E., Study of the interaction between salivary proline-rich proteins and a polyphenol by 1H-NMR spectroscopy. Eur. J. Biochem., 219, 923-935 (1994).
73) Higashi K., Yamamoto K., Pandey M. K., Mroue K. H., Moribe K., Yamamoto K., Ramamoorthy A., Insights into atomic-level interaction between mefenamic acid and eudragit EPO in a supersaturated solution by high-resolution magic-angle spinning NMR spectroscopy. Mol. Pharm., 11, 351-357 (2014).
74) Macura S., Ernst R. R., Elucidation of cross relaxation in liquids by two-dimensional N.M.R.
spectroscopy. Mole. Phys., 41, 95-117 (1980).
75) Tanida S., Kurokawa T., Sato H., Kadota K., Tozuka Y., Evaluation of the micellization mechanism of an amphipathic graft copolymer with enhanced solubility of ipriflavone. Chem. Pharm. Bull., 64, 68-72 (2016).
76) Hasegawa A., Taguchi M., Suzuki R., Miyata T., Nakagawa H., Sugimoto I., Supersaturation mechanism of drugs from solid dispersions with enteric coating agents. Chem. Pharm. Bull., 36, 4941-4950 (1988).
77) Somasundaran P., Krishnakumar S., Adsorption of surfactants and polymers at the solid-liquid interface.
Colloids Surf. Physicochem. Eng. Aspects, 123, 491-513 (1997).
78) Kubota N., Effect of impurities on the growth kinetics of crystals. Cryst. Res. Technol., 36, 749-769 (2001).
79) Gift A. D., Luner P. E., Luedeman L., Taylor L. S., Influence of polymeric excipients on crystal hydrate formation kinetics in aqueous slurries. J. Pharm. Sci., 97, 5198-5211 (2008).
80) Warren D. B., Benameur H., Porter C. J., Pouton C. W., Using polymeric precipitation inhibitors to improve the absorption of poorly water-soluble drugs: A mechanistic basis for utility. J. Drug Target., 18, 704-731 (2010).
81) Megrab N. A., Williams A. C., Barry B. W., Oestradiol permeation through human skin and silastic membrane: effects of propylene glycol and supersaturation. J. Control. Release, 36, 277-294 (1995).
82) Overhoff K. A., McConville J. T., Yang W., Johnston K. P., Peters J. I., Williams R. O., 3rd, Effect of stabilizer on the maximum degree and extent of supersaturation and oral absorption of tacrolimus made by ultra-rapid freezing. Pharm. Res., 25, 167-175 (2008).
83) Li Y., Pang H., Guo Z., Lin L., Dong Y., Li G., Lu M., Wu C., Interactions between drugs and polymers influencing hot melt extrusion. J. Pharm. Pharmacol., 66, 148-166 (2014).
84) Li S., Tian Y., Jones D. S., Andrews G. P., Optimising drug solubilisation in amorphous polymer dispersions: rational selection of hot-melt extrusion processing parameters. AAPS PharmSciTech, 17, 200-213 (2016).
85) Repka M. A., Bandari S., Kallakunta V. R., Vo A. Q., McFall H., Pimparade M. B., Bhagurkar A. M., Melt extrusion with poorly soluble drugs - An integrated review. Int. J. Pharm., 535, 68-85 (2018).
86) Grymonpre W., De Jaeghere W., Peeters E., Adriaensens P., Remon J. P., Vervaet C., The impact of hot-melt extrusion on the tableting behaviour of polyvinyl alcohol. Int. J. Pharm., 498, 254-262 (2016).
87) Greenhalgh D. J., Williams A. C., Timmins P., York P., Solubility parameters as predictors of miscibility in solid dispersions. J. Pharm. Sci., 88, 1182-1190 (1999).
88) Marsac P. J., Li T., Taylor L. S., Estimation of drug-polymer miscibility and solubility in amorphous solid dispersions using experimentally determined interaction parameters. Pharm. Res., 26, 139-151 (2009).
89) Gupta J., Nunes C., Vyas S., Jonnalagadda S., Prediction of solubility parameters and miscibility of pharmaceutical compounds by molecular dynamics simulations. J. Phys. Chem. B, 115, 2014-2023 (2011).
90) Rumondor A. C., Ivanisevic I., Bates S., Alonzo D. E., Taylor L. S., Evaluation of drug-polymer miscibility in amorphous solid dispersion systems. Pharm. Res., 26, 2523-2534 (2009).
91) Li J., Lee I. W., Hwa Shin G., Chen X., Jin Park H., Curcumin-Eudragit® E PO solid dispersion: A simple and potent method to solve the problems of curcumin. Eur. J. Pharm. Biopharm., 94, 322-332 (2015).
92) Hengsawas Surasarang S., Keen J. M., Huang S., Zhang F., McGinity J. W., Williams R. O., 3rd, Hot melt extrusion versus spray drying: hot melt extrusion degrades albendazole. Drug. Dev. Ind. Pharm., 43, 797-811 (2017).
93) Keller A., Cheng S. Z. D., The role of metastability in polymer phase transitions. Polymer, 39, 4461-4487 (1998).
94) Tian Y., Booth J., Meehan E., Jones D. S., Li S., Andrews G. P., Construction of drug-polymer thermodynamic phase diagrams using Flory-Huggins interaction theory: identifying the relevance of temperature and drug weight fraction to phase separation within solid dispersions. Mol. Pharm., 10, 236-248 (2013).
95) Chokshi R. J., Sandhu H. K., Iyer R. M., Shah N. H., Malick A. W., Zia H., Characterization of physico-mechanical properties of indomethacin and polymers to assess their suitability for hot-melt extrusion processs as a means to manufacture solid dispersion/solution. J. Pharm. Sci., 94, 2463-2474 (2005).
96) Matsumoto T., Zografi G., Physical properties of solid molecular dispersions of indomethacin with poly(vinylpyrrolidone) and poly(vinylpyrrolidone-co-vinyl-acetate) in relation to indomethacin crystallization. Pharm. Res., 16, 1722-1728 (1999).
97) Huang Y., Dai W. G., Fundamental aspects of solid dispersion technology for poorly soluble drugs. Acta.
Pharm. Sin. B, 4, 18-25 (2014).
98) DeBoyace K., Wildfong P. L. D., The application of modeling and prediction to the formation and stability of amorphous solid dispersions. J. Pharm. Sci., 107, 57-74 (2018).
99) Sun Y., Tao J., Zhang G. G., Yu L., Solubilities of crystalline drugs in polymers: an improved analytical method and comparison of solubilities of indomethacin and nifedipine in PVP, PVP/VA, and PVAc. J.
Pharm. Sci., 99, 4023-4031 (2010).
100) Yoo S. U., Krill S. L., Wang Z., Telang C., Miscibility/stability considerations in binary solid dispersion systems composed of functional excipients towards the design of multi-component amorphous systems. J.
Pharm. Sci., 98, 4711-4723 (2009).
101) Chen Y., Liu C., Chen Z., Su C., Hageman M., Hussain M., Haskell R., Stefanski K., Qian F.,
Drug-polymer-water interaction and its implication for the dissolution performance of amorphous solid dispersions. Mol. Pharm., 12, 576-589 (2015).
102) Lin D., Huang Y., A thermal analysis method to predict the complete phase diagram of drug-polymer solid dispersions. Int. J. Pharm., 399, 109-115 (2010).
103) Nikitine C., Rodier E., Sauceau M., Fages J., Residence time distribution of a pharmaceutical grade polymer melt in a single screw extrusion process. Chem. Eng. Res. Des., 87, 809-816 (2009).
104) Patil H., Tiwari R. V., Repka M. A., Hot-melt extrusion: from theory to application in pharmaceutical formulation. AAPS PharmSciTech, 17, 20-42 (2016).
105) POVAL, Effects of the degree of polymerization and degree of hydrolysis
www.j-vp.co.jp/english/product/pva/pdf/kenka01.pdf (accessed 18. 01. 01). (2010).
106) Sun D. D., Lee P. I., Evolution of supersaturation of amorphous pharmaceuticals: nonlinear rate of supersaturation generation regulated by matrix diffusion. Mol. Pharm., 12, 1203-1215 (2015).
107) Vasconcelos T., Marques S., das Neves J., Sarmento B., Amorphous solid dispersions: Rational selection of a manufacturing process. Adv. Drug Deliv. Rev., 100, 85-101 (2016).
108) Dinunzio J. C., Brough C., Hughey J. R., Miller D. A., Williams R. O., 3rd, McGinity J. W., Fusion production of solid dispersions containing a heat-sensitive active ingredient by hot melt extrusion and Kinetisol dispersing. Eur. J. Pharm. Biopharm., 74, 340-351 (2010).
109) DiNunzio J. C., Brough C., Miller D. A., Williams R. O., 3rd, McGinity J. W., Applications of KinetiSol® dispersing for the production of plasticizer free amorphous solid dispersions. Eur. J. Pharm. Sci., 40, 179-187 (2010).
110) Ellenberger D. J., Miller D. A., Williams R. O., 3rd, Expanding the application and formulation space of amorphous solid dispersions with KinetiSol®: a Review. AAPS PharmSciTech, 19, 1933-1956 (2018).
111) Ghebremeskel A. N., 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., 23, 1928-1936 (2006).
112) Djuris J., Ioannis N., Ibric S., Djuric Z., Kachrimanis K., Effect of composition in the development of carbamazepine hot-melt extruded solid dispersions by application of mixture experimental design. J.
Pharm. Pharmacol., 66, 232-243 (2014).
113) Quaroni G. M. G., Gennari C. G. M., Cilurzo F., Ducouret G., Creton C., Minghetti P., Tuning the rheological properties of an ammonium methacrylate copolymer for the design of adhesives suitable for transdermal patches. Eur. J. Pharm. Sci., 111, 238-246 (2018).
114) Matet M., Heuzey M. C., Pollet E., Ajji A., Averous L., Innovative thermoplastic chitosan obtained by thermo-mechanical mixing with polyol plasticizers. Carbohydr. Polym., 95, 241-251 (2013).
115) ICH PHARMACEUTICAL DEVELOPMENT Q8 (R2)
www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q8_R1/Step4/Q8_R2_Guide line.pdf (accessed 18. 05. 04).
116) Gu B., Linehan B., Tseng Y.-C., Optimization of the Büchi B-90 spray drying process using central composite design for preparation of solid dispersions. Int. J. Pharm., 491, 208-217 (2015).
117) Kanojia G., Willems G. J., Frijlink H. W., Kersten G. F., Soema P. C., Amorij J. P., A design of
experiment approach to predict product and process parameters for a spray dried influenza vaccine. Int. J.
Pharm., 511, 1098-1111 (2016).
118) Medarevic D. P., Kleinebudde P., Djuris J., Djuric Z., Ibric S., Combined application of mixture experimental design and artificial neural networks in the solid dispersion development. Drug Dev. Ind.
Pharm., 42, 389-402 (2016).
119) Davis M. T., Potter C. B., Mohammadpour M., Albadarin A. B., Walker G. M., Design of spray dried ternary solid dispersions comprising itraconazole, soluplus and HPMCP: Effect of constituent compositions. Int. J. Pharm., 519, 365-372 (2017).
120) Politis S. N., Rekkas D. M., Development of a fast, lean and agile direct pelletization process using experimental design techniques. Drug Dev. Ind. Pharm., 43, 545-557 (2017).