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Hot Melt Ekstrüzyonda Son Gelişmeler ve Uygulamaları

Yıl 2022, Cilt: 42 Sayı: 1, 31 - 45, 01.03.2022
https://doi.org/10.52794/hujpharm.961794

Öz

Endüstriyel uyumluluk, üretim süreci, formülasyon ve geliştirmenin sonucuyla birlikte, Hot Melt Ekstrüzyon (HME) de kabulü genişletti. Endüstriyel uyarlanabilirliğin bir sonucu olarak, ilaç araştırma ve geliştirmenin bir parçası olarak geniş bir yelpazede kendini geliştirmiştir. Yeni ilaç varlıkları, zayıf biyofarmasötik özellikler, toksisiteler ve etkinlik eksikliği dahil olmak üzere formülasyon geliştirme sırasında başarısızlıklar veya gecikmelerle karşı karşıyadır. Bu tür engelleri aşmak için en çok tercih edilen HME tekniğidir. Konvansiyonel tekniklerle karşılaştırıldığında, uygun prosesi, solvent içermeyen yapısı, uygun maliyetli ve on-line üretimi nedeniyle kullanımı giderek artmaktadır. Farklı uygulamalar elde etmek için, ekipmanın tasarımı değiştirilerek ve değiştirilmiş bir işleme koşulu uyarlanarak çeşitli dozaj formları üretilebilir

Kaynakça

  • [1] Cruz, CN., Madurawe, R., Pavurala, N., Chatterjee, S. Control strategy considerations for continuous manufacturing using hot melt extrusion, in: Ghebre-Sellassie, I., Martin, C., Zhang, F., DiNunzio, J., (Eds.), Pharmaceutical Extrusion Technology, second ed., CRC Press, 2018:53–70.
  • [2] Maniruzzaman, M, Nokhodchi, A. Continuous manufacturing via hot-melt extrusion and scale up: regulatory matters. Drug Discov Today. 2017;22:340-351.
  • [3] El-Egakey, MA., Soliva, M., Speiser P. Hot extruded dosage forms. I. Technology and dissolution kinetics of polymeric matrices. Pharm Acta Helv. 1971;46:31.
  • [4] Lawal, A., Kalyon, D. Mechanisms of mixing in single and Co-rotating twin-screw extruders. Polym Eng Sci. 1995;35:1325-1338.
  • [5] Patil, H., Tiwari RV, Repka MA. Hot-melt extrusion: from theory to application in pharmaceutical formulation, AAPS PharmSciTech 2016;17:20-42.
  • [6] Leister, D., Geilen, T., Geissler, T. Twin-screw extruders for pharmaceutical hotmelt extrusion: technology, techniques and practices, in: Douroumis, D., (Ed.), HotMelt Extrusion: Pharmaceutical Applications, John Wiley & Sons, Ltd., 2012;23-42.
  • [7] Martin, C. Twin-screw extruders for pharmaceutical products from a technical and historical perspective, in: Ghebre-Sellassie, I., Martin, C., Zhang, F., DiNunzio J., (Eds.), Pharmaceutical Extrusion Technology. CRC Press, 2018;1-35.
  • [8] Breitenbach, J. Melt extrusion: from process to drug delivery technology. Eur J Pharm Biopharm. 2002;54:107-117.
  • [9] Listro, T., Bessemer, B. Shape extrusion - extruded implantable drug delivery devices: materials, applications, and processing, in: Ghebre-Sellassie, I., Martin, C., E., Zhang, F., DiNunzio J. (Eds.), Pharmaceutical Extrusion Technology, CRC Press, 2018, pp. 231-246.
  • [10] Case, C., C., Huber, A., Nickel, K. Melt pelletization and size reduction: powder to pellets and powder to powder, in: Ghebre-Sellassie, I., Martin, C., Zhang, F., DiNunzio J. (Eds.), Pharmaceutical Extrusion Technology, second ed., CRC Press, 2018, pp. 183-196.
  • [11] Steiner, R., Haight, B. Extruder design, in: Ghebre-Sellassie, I., Martin, C., Zhang, F., DiNunzio J. (Eds.), Pharmaceutical Extrusion Technology, second ed., CRC Press, 2003, pp. 37-52.
  • [12] Miyagawa, Y., Okabe, T., Yamaguchi, Y., Miyajima, M., Sato, H., Sunada, H. Controlled-release of diclofenac sodium from wax matrix granule, Int J Pharm. 1996;138:215-224.
  • [13] Stankovi´c, M., Frijlink, H.W., Hinrichs, W.L. Polymeric formulations for drug release prepared by hot melt extrusion: application and characterization. Drug Discov Today 2015;20:812-823.
  • [14] Aharoni, S., M. Increased glass transition temperature in motionally constrained semicrystalline polymers. Polym Adv Technol. 1998;9:169–201.
  • [15] 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;91:1678-1685.
  • [16] Verreck, G., Decorte, A., Li, H., Tomasko, D., Arien, A., Peeters, J., Rombaut, P., Van den Mooter, G., Brewster, M., E. The effect of pressurized carbon dioxide as a plasticizer and foaming agent on the hot melt extrusion process and extrudate properties of pharmaceutical polymers. J Supercrit. Fluids 2006;38:383–391.
  • [17] Zhang, J., Vo, A.Q., Feng, X., Bandari, S., Repka, M. A. Pharmaceutical additive manufacturing: a novel tool for complex and personalized drug delivery systems. AAPS PharmSciTech. 2018;19: 3388-3402.
  • [18] Pandey, M., Choudhury, H., Fern, J. L. C, Kee, A. T. K, Kou, J., Jing, J. L. J., Her, H. C., Yong, H. S., Ming, H. C., Bhattamisra, S. K. 3D printing for oral drug delivery: a new tool to customize drug delivery. Drug Dev Transl Res. 2020;1-16.
  • [19] Jamroz, W., Kurek,´ M., Łyszczarz, E., Szafraniec, J., Knapik-Kowalczuk, J., Syrek, K., Paluch, M., Jachowicz, R. 3D printed orodispersible films with aripiprazole. Int J Pharm. 2017;533:413–420.
  • [20] Palekar, S., Nukala, P.K., Mishra, S.M., Kipping, T., Patel, K. Application of 3D printing technology and quality by design approach for development of age appropriate pediatric formulation of baclofen. Int J Pharm. 2019; 556:106-116.
  • [21] Scoutaris, N., Ross, S.A., Douroumis, D. 3D printed “Starmix” drug loaded dosage forms for paediatric applications. Pharm. Res. 2018;35:34.
  • [22] Gültekin, H., E., Tort, S., Acartürk, F. An effective technology for the development of immediate release solid dosage forms containing low-dose drug: fused deposition modeling 3D printing. Pharm Res 2019;36:128.
  • [23] Gurunath, S., Pradeep, K., S., Basavaraj, N., K., Patil, P., A. Amorphous solid dispersion method for improving oral bioavailability of poorly water-soluble drugs. J Pharm Res. 2013;6:476-480.
  • [24] Butreddy, A., Bandari, S., Repka, M., A. Quality-by-design in hot melt extrusion based amorphous solid dispersions: an industrial perspective on product development. Eur J Pharmaceut Sci. 2020;10:55-56.
  • [25] Sarabu, S., Kallakunta, V. R., Bandari, S., Batra, A., Bi, V., Durig, T., Zhang, F., Repka, M., A. Hypromellose acetate succinate based amorphous solid dispersions via hot melt extrusion: effect of drug physicochemical properties. Carbohydr Polym. 2020;115-828.
  • [26]. Nukala, P., K, Palekar, S., Patki, M., Patel, K. Abuse deterrent immediate release egg shaped tablet (egglets) using 3D printing technology: quality by design to optimize drug release and extraction. AAPS PharmSciTech. 2019;20:80.
  • [27] Vynckier, A., K., Dierickx, L., Voorspoels, J., Gonnissen, Y., Remon, J., P.,, Vervaet C. Hot-melt co-extrusion: requirements, challenges and opportunities for pharmaceutical applications. J Pharm Pharmacol. 2013;66:167-179. [28] Almajaan, A., Healy, A., M,, Jones, D., Gilvary, G., Andrews, G., Kelleher, J., Li, S., Tian, Y., Zo´e, S., L. Hot-melt co-extrusion technology as a manufacturing platform for anti-hypertensive fixed-dose combinations. Br J Pharmacol. 2019;4.
  • [29] Karki, S., Kim, H., Na, S., J., Shin, D., Jo, K., Lee, J. Thin films as an emerging platform for drug delivery. Asian J Pharm Sci. 2016;11:559–574.
  • [30] Kayumba., P., C., Huyghebaert, N., Cordella, C., Ntawukuliryayo, J., D., Vervaet, C., Remon, J., P. Quinine sulphate pellets for flexible pediatric drug dosing: formulation development and evaluation of taste-masking efficiency using the electronic tongue. Eur. J. Pharm. Biopharm. 2007;66:460–465.
  • [31] Vithani, K., Douroumis, D. Hot-melt extruded lipidic pellets for pediatric applications: an investigation of the effects and stability on drug dissolution. J Drug Deliv Sci Technol. 2019;49:43-49.
  • [32] Frake, P., Greenhalgh, D., Grierson, S., M., Hempenstall, J., M., Rudd, D. R. Process control and end-point determination of a fluid bed granulation by application of near infra-red spectroscopy. Int J Pharm. 1997;151:75-80.
  • [33] Okumu, F., W., Cleland, J., L. Implants and injectables, in: M. Rathbone, J. Hadgraft (Eds.), Modified-Release Drug Delivery Technology, first ed., CRC Press, Boca Raton, 2002, pp. 633–638.
  • [34] Mendonsa, N., S., Murthy, S., N., Hashemnejad, S., M., Kundu, S., Zhang, F., Repka, M., A. Development of poloxamer gel formulations via hot-melt extrusion technology. Int J Pharm. 2018;537:122–131.
  • [35] Mendonsa, N., S., Pradhan, A., Sharma, P., Prado, R., M., Murthy, S., N., Kundu, S., Repka, M., A. A quality by design approach to develop topical creams via hot-melt extrusion technology. Eur J Pharmaceut Sci. 2019;136:104948.
  • [36] Marreto, R., N., Cardoso, G., dos Santos Souza, B., Martin-Pastor, M., Cunha-Filho, M., Taveira, S.F, Concheiro, A., Alvarez-Lorenzo, C. Hot melt-extrusion improves the properties of cyclodextrin-based poly (pseudo) rotaxanes for transdermal formulation. Int J Pharm. 2020; 119510.
  • [37] Lu, Y., Park, K. Microencapsulation: methods and pharmaceutical applications, in: fourth ed., in: J. Swarbrick (Ed.), Encyclopedia of Pharmaceutical Science and Technology. vol. 1, CRC Press, Boca Raton (USA), 2012;1–13.
  • [38] Ghosh, S. K., Functional coatings and microencapsulation: a general perspective, in: S. K. Ghosh (Ed.), Functional Coatings, Wiley-VCH, Weinheim, 2006; 1=28.
  • [39] Khor, C. M., Ng, W., K., Kanaujia, P., Chan, K., P., Dongm, Y. Hot-melt extrusion microencapsulation of quercetin for taste-masking. J Microencapsul 2017;34:29–37.
  • [40] Constantinides, P., P. Lipid microemulsions for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects. Pharm Res. 1995;12:1561–1572.
  • [41] Joyce, P., Dening, T., J., Meola, T., R. Schultz H., B. Holm R, Thomas N, Prestidge C A. Solidification to improve the biopharmaceutical performance of SEDDS: opportunities and challenges. Adv Drug Deliv Rev. 2019;142:102–117.
  • [42] Boisseau, P., Loubaton, B. Nanomedicine: nanotechnology in medicine. C R Phys 2011;12: 620–636.
  • [43] Patil, H., Feng X., Ye, X., Majumdar S, Repka MA. Continuous production of fenofibrate solid lipid nanoparticles by hot-melt extrusion technology: a systematic study based on a quality by design approach. AAPS J. 2015;17:194–205.
  • [44] Douroumis, D., Ross, S. A., Nokhodchi A. Advanced methodologies for cocrystal synthesis. Adv Drug Deliv Rev 2017;117:178–195.
  • [45] Fernandes, G., J., Rathnanand, M. Formulation optimization for gastroretentive drug delivery system of carvedilol cocrystals using design of experiment. J Pharm\ Innov. 2019; 1–12.

Recent Advances in Hot Melt Extrusion and its Applications

Yıl 2022, Cilt: 42 Sayı: 1, 31 - 45, 01.03.2022
https://doi.org/10.52794/hujpharm.961794

Öz

Over the decades with the outcome of industrial compliance, manufacturing process, formulation and development, Hot Melt Extrusion (HME) has also expanded the acceptance. As a result of industrial adaptability, it has developed itself in a wide range as a part of pharmaceutical research and development. New drug entities face failures or delays during formulation development, including poor biopharmaceutical properties, toxicities and lack of efficacy. To overcome such obstacles, HME technique is most preferred one. In comparison to conventional techniques, its use has been increasing because of its convenient process, solvent free nature, cost effective and on-line manufacturing. For achieving different applications several dosage forms can be produced by altering the design of equipment and adapting a modified processing condition.

Kaynakça

  • [1] Cruz, CN., Madurawe, R., Pavurala, N., Chatterjee, S. Control strategy considerations for continuous manufacturing using hot melt extrusion, in: Ghebre-Sellassie, I., Martin, C., Zhang, F., DiNunzio, J., (Eds.), Pharmaceutical Extrusion Technology, second ed., CRC Press, 2018:53–70.
  • [2] Maniruzzaman, M, Nokhodchi, A. Continuous manufacturing via hot-melt extrusion and scale up: regulatory matters. Drug Discov Today. 2017;22:340-351.
  • [3] El-Egakey, MA., Soliva, M., Speiser P. Hot extruded dosage forms. I. Technology and dissolution kinetics of polymeric matrices. Pharm Acta Helv. 1971;46:31.
  • [4] Lawal, A., Kalyon, D. Mechanisms of mixing in single and Co-rotating twin-screw extruders. Polym Eng Sci. 1995;35:1325-1338.
  • [5] Patil, H., Tiwari RV, Repka MA. Hot-melt extrusion: from theory to application in pharmaceutical formulation, AAPS PharmSciTech 2016;17:20-42.
  • [6] Leister, D., Geilen, T., Geissler, T. Twin-screw extruders for pharmaceutical hotmelt extrusion: technology, techniques and practices, in: Douroumis, D., (Ed.), HotMelt Extrusion: Pharmaceutical Applications, John Wiley & Sons, Ltd., 2012;23-42.
  • [7] Martin, C. Twin-screw extruders for pharmaceutical products from a technical and historical perspective, in: Ghebre-Sellassie, I., Martin, C., Zhang, F., DiNunzio J., (Eds.), Pharmaceutical Extrusion Technology. CRC Press, 2018;1-35.
  • [8] Breitenbach, J. Melt extrusion: from process to drug delivery technology. Eur J Pharm Biopharm. 2002;54:107-117.
  • [9] Listro, T., Bessemer, B. Shape extrusion - extruded implantable drug delivery devices: materials, applications, and processing, in: Ghebre-Sellassie, I., Martin, C., E., Zhang, F., DiNunzio J. (Eds.), Pharmaceutical Extrusion Technology, CRC Press, 2018, pp. 231-246.
  • [10] Case, C., C., Huber, A., Nickel, K. Melt pelletization and size reduction: powder to pellets and powder to powder, in: Ghebre-Sellassie, I., Martin, C., Zhang, F., DiNunzio J. (Eds.), Pharmaceutical Extrusion Technology, second ed., CRC Press, 2018, pp. 183-196.
  • [11] Steiner, R., Haight, B. Extruder design, in: Ghebre-Sellassie, I., Martin, C., Zhang, F., DiNunzio J. (Eds.), Pharmaceutical Extrusion Technology, second ed., CRC Press, 2003, pp. 37-52.
  • [12] Miyagawa, Y., Okabe, T., Yamaguchi, Y., Miyajima, M., Sato, H., Sunada, H. Controlled-release of diclofenac sodium from wax matrix granule, Int J Pharm. 1996;138:215-224.
  • [13] Stankovi´c, M., Frijlink, H.W., Hinrichs, W.L. Polymeric formulations for drug release prepared by hot melt extrusion: application and characterization. Drug Discov Today 2015;20:812-823.
  • [14] Aharoni, S., M. Increased glass transition temperature in motionally constrained semicrystalline polymers. Polym Adv Technol. 1998;9:169–201.
  • [15] 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;91:1678-1685.
  • [16] Verreck, G., Decorte, A., Li, H., Tomasko, D., Arien, A., Peeters, J., Rombaut, P., Van den Mooter, G., Brewster, M., E. The effect of pressurized carbon dioxide as a plasticizer and foaming agent on the hot melt extrusion process and extrudate properties of pharmaceutical polymers. J Supercrit. Fluids 2006;38:383–391.
  • [17] Zhang, J., Vo, A.Q., Feng, X., Bandari, S., Repka, M. A. Pharmaceutical additive manufacturing: a novel tool for complex and personalized drug delivery systems. AAPS PharmSciTech. 2018;19: 3388-3402.
  • [18] Pandey, M., Choudhury, H., Fern, J. L. C, Kee, A. T. K, Kou, J., Jing, J. L. J., Her, H. C., Yong, H. S., Ming, H. C., Bhattamisra, S. K. 3D printing for oral drug delivery: a new tool to customize drug delivery. Drug Dev Transl Res. 2020;1-16.
  • [19] Jamroz, W., Kurek,´ M., Łyszczarz, E., Szafraniec, J., Knapik-Kowalczuk, J., Syrek, K., Paluch, M., Jachowicz, R. 3D printed orodispersible films with aripiprazole. Int J Pharm. 2017;533:413–420.
  • [20] Palekar, S., Nukala, P.K., Mishra, S.M., Kipping, T., Patel, K. Application of 3D printing technology and quality by design approach for development of age appropriate pediatric formulation of baclofen. Int J Pharm. 2019; 556:106-116.
  • [21] Scoutaris, N., Ross, S.A., Douroumis, D. 3D printed “Starmix” drug loaded dosage forms for paediatric applications. Pharm. Res. 2018;35:34.
  • [22] Gültekin, H., E., Tort, S., Acartürk, F. An effective technology for the development of immediate release solid dosage forms containing low-dose drug: fused deposition modeling 3D printing. Pharm Res 2019;36:128.
  • [23] Gurunath, S., Pradeep, K., S., Basavaraj, N., K., Patil, P., A. Amorphous solid dispersion method for improving oral bioavailability of poorly water-soluble drugs. J Pharm Res. 2013;6:476-480.
  • [24] Butreddy, A., Bandari, S., Repka, M., A. Quality-by-design in hot melt extrusion based amorphous solid dispersions: an industrial perspective on product development. Eur J Pharmaceut Sci. 2020;10:55-56.
  • [25] Sarabu, S., Kallakunta, V. R., Bandari, S., Batra, A., Bi, V., Durig, T., Zhang, F., Repka, M., A. Hypromellose acetate succinate based amorphous solid dispersions via hot melt extrusion: effect of drug physicochemical properties. Carbohydr Polym. 2020;115-828.
  • [26]. Nukala, P., K, Palekar, S., Patki, M., Patel, K. Abuse deterrent immediate release egg shaped tablet (egglets) using 3D printing technology: quality by design to optimize drug release and extraction. AAPS PharmSciTech. 2019;20:80.
  • [27] Vynckier, A., K., Dierickx, L., Voorspoels, J., Gonnissen, Y., Remon, J., P.,, Vervaet C. Hot-melt co-extrusion: requirements, challenges and opportunities for pharmaceutical applications. J Pharm Pharmacol. 2013;66:167-179. [28] Almajaan, A., Healy, A., M,, Jones, D., Gilvary, G., Andrews, G., Kelleher, J., Li, S., Tian, Y., Zo´e, S., L. Hot-melt co-extrusion technology as a manufacturing platform for anti-hypertensive fixed-dose combinations. Br J Pharmacol. 2019;4.
  • [29] Karki, S., Kim, H., Na, S., J., Shin, D., Jo, K., Lee, J. Thin films as an emerging platform for drug delivery. Asian J Pharm Sci. 2016;11:559–574.
  • [30] Kayumba., P., C., Huyghebaert, N., Cordella, C., Ntawukuliryayo, J., D., Vervaet, C., Remon, J., P. Quinine sulphate pellets for flexible pediatric drug dosing: formulation development and evaluation of taste-masking efficiency using the electronic tongue. Eur. J. Pharm. Biopharm. 2007;66:460–465.
  • [31] Vithani, K., Douroumis, D. Hot-melt extruded lipidic pellets for pediatric applications: an investigation of the effects and stability on drug dissolution. J Drug Deliv Sci Technol. 2019;49:43-49.
  • [32] Frake, P., Greenhalgh, D., Grierson, S., M., Hempenstall, J., M., Rudd, D. R. Process control and end-point determination of a fluid bed granulation by application of near infra-red spectroscopy. Int J Pharm. 1997;151:75-80.
  • [33] Okumu, F., W., Cleland, J., L. Implants and injectables, in: M. Rathbone, J. Hadgraft (Eds.), Modified-Release Drug Delivery Technology, first ed., CRC Press, Boca Raton, 2002, pp. 633–638.
  • [34] Mendonsa, N., S., Murthy, S., N., Hashemnejad, S., M., Kundu, S., Zhang, F., Repka, M., A. Development of poloxamer gel formulations via hot-melt extrusion technology. Int J Pharm. 2018;537:122–131.
  • [35] Mendonsa, N., S., Pradhan, A., Sharma, P., Prado, R., M., Murthy, S., N., Kundu, S., Repka, M., A. A quality by design approach to develop topical creams via hot-melt extrusion technology. Eur J Pharmaceut Sci. 2019;136:104948.
  • [36] Marreto, R., N., Cardoso, G., dos Santos Souza, B., Martin-Pastor, M., Cunha-Filho, M., Taveira, S.F, Concheiro, A., Alvarez-Lorenzo, C. Hot melt-extrusion improves the properties of cyclodextrin-based poly (pseudo) rotaxanes for transdermal formulation. Int J Pharm. 2020; 119510.
  • [37] Lu, Y., Park, K. Microencapsulation: methods and pharmaceutical applications, in: fourth ed., in: J. Swarbrick (Ed.), Encyclopedia of Pharmaceutical Science and Technology. vol. 1, CRC Press, Boca Raton (USA), 2012;1–13.
  • [38] Ghosh, S. K., Functional coatings and microencapsulation: a general perspective, in: S. K. Ghosh (Ed.), Functional Coatings, Wiley-VCH, Weinheim, 2006; 1=28.
  • [39] Khor, C. M., Ng, W., K., Kanaujia, P., Chan, K., P., Dongm, Y. Hot-melt extrusion microencapsulation of quercetin for taste-masking. J Microencapsul 2017;34:29–37.
  • [40] Constantinides, P., P. Lipid microemulsions for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects. Pharm Res. 1995;12:1561–1572.
  • [41] Joyce, P., Dening, T., J., Meola, T., R. Schultz H., B. Holm R, Thomas N, Prestidge C A. Solidification to improve the biopharmaceutical performance of SEDDS: opportunities and challenges. Adv Drug Deliv Rev. 2019;142:102–117.
  • [42] Boisseau, P., Loubaton, B. Nanomedicine: nanotechnology in medicine. C R Phys 2011;12: 620–636.
  • [43] Patil, H., Feng X., Ye, X., Majumdar S, Repka MA. Continuous production of fenofibrate solid lipid nanoparticles by hot-melt extrusion technology: a systematic study based on a quality by design approach. AAPS J. 2015;17:194–205.
  • [44] Douroumis, D., Ross, S. A., Nokhodchi A. Advanced methodologies for cocrystal synthesis. Adv Drug Deliv Rev 2017;117:178–195.
  • [45] Fernandes, G., J., Rathnanand, M. Formulation optimization for gastroretentive drug delivery system of carvedilol cocrystals using design of experiment. J Pharm\ Innov. 2019; 1–12.
Toplam 44 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık ve İlaç Bilimleri
Bölüm Review Articles
Yazarlar

Ratnaprabha Kinikar Bu kişi benim

Ashwin Kuchekar

Yayımlanma Tarihi 1 Mart 2022
Kabul Tarihi 24 Kasım 2021
Yayımlandığı Sayı Yıl 2022 Cilt: 42 Sayı: 1

Kaynak Göster

Vancouver Kinikar R, Kuchekar A. Recent Advances in Hot Melt Extrusion and its Applications. HUJPHARM. 2022;42(1):31-45.