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Determination of Critical Formulation Temperatures of Mannitol Solutions Containing Iron, Potassium, Magnesium and Sodium Salts by Differential Thermal Analysis (DTA) and Freeze Dry Microscope (FDM)

Year 2020, Volume: 2 Issue: 2, 39 - 44, 30.12.2020

Gülseren Yıldız Öz

Abstract

The lyophilization process, in which the kinetic clock of a substance is slowed, is specific for each substance or solution. There are some important state-change temperatures specific to each substance. It is necessary to determine the collapse temperature (Tc), eutectic point (Teu) and glass transition (Tg), to prepare a prescription for quality drying and to define the material. The aim of the study is to determine the critical temperature values required to form drying recipes of solutions containing mannitol and different mineral salts. For this purpose, critical formulation temperatures of mannitol solutions containing iron, potassium, magnesium and sodium salts were determined using Differential Thermal Analysis (DTA) device and Freeze Dry Microscope (FDM). At the end of the study, Teu and Tc values of mannitol were found to be high. Also, it was concluded that salts reduce Teu and Tc values. The Teu and Tc values obtained for mannitol represent a successful result in terms of lyophilization quality. Salts added to the mannitol solution require primary drying to be completed at lower temperatures. This result represents a difficult and costly primary drying process. 

Keywords

Lyophilization Mannitol Mineral Salts

References

  • Adams GDJ, Cook I, Ward KR (2015) The Principles of Freeze-Drying. Methods Mol Biol 1257:121-143. https://doi.org/10.1007/978-1-4939-2193-5_4
  • Andrade ÂL, Militani IA, de Almeida KJ, Belchior JC, dos Reis SC, Costa e Silva RMF, Domingues RZ (2018) Theoretical and Experimental Studies of the Controlled Release of Tetracycline Incorporated into Bioactive Glasses. AAPS PharmSciTech 19 (3), 1287-1296. https://doi.org/10.1208/s12249-017-0931-x
  • Arshad M S, Smith G, Polygalov E, Ermolina I (2014). Through-vial impedance spectroscopy of critical events during the freezing stage of the lyophilization cycle: the example of the impact of sucrose on the crystallization of mannitol. Eur. J Pharm Biopharm 87, 598–605. https://doi.org/10.1016/j.ejpb.2014.05.005
  • Cavatur RK, Vemuri NM, Pyne A, Chrzan Z, Toledo-Velasquez D, Suryanarayanan R (2002) Crystallization behavior of mannitol in frozen aqueous solutions. Pharm Res, 19 (6), 894–900. https://doi.org/10.1023/a:1016177404647
  • Chang BS, Randall CS (1992). Use of subambient thermal analysis to optimize protein lyophilization. Cryobiology, 29 (5), 632–56. https://doi.org/10.1016/0011-2240(92)90067-C
  • Day JG, Stacey GN (2007) Cryopreservation and Freeze- Drying Protocols, Human Press, New Jersey.
  • Hawe A, Frieß W (2006) Impact of freezing procedure and annealing on the physico-chemical properties and the formation of mannitol hydrate in mannitol-sucrose-NaCl formulations. Eur J Pharm Biopharm 64, 316–325. https://doi.org/10.1016/j.ejpb.2006.06.002
  • Horn J, Friess W (2018) Detection of Collapse and Crystallization of Saccharide, Protein, and Mannitol Formulations by Optical Fibers in Lyophilization. Frontiers in Chemistry 6 (4) 1-9 https://doi.org/10.3389/fchem.2018.00004
  • Ito K (1971) Freeze drying of pharmaceuticals. Eutectic temperature and collapse temperature of solute matrix upon freeze drying of three component systems. Chem Pharm Bull 19 (6), 1095–102. https://doi.org/10.1248/cpb.19.1095
  • Izutsu K, Kojima S(2002) Excipient crystallinity and its protein-structurestabilizing effect during freeze-drying. J Pharm Pharmacol. 54, 1033–1039. https://doi.org/10.1211/002235702320266172
  • Izutsu K, Yoshioka S, Terao T (1994) Effect of mannitol crystallinity on the stabilization of enzymes during freeze-drying. Chem Pharm Bull (Tokyo) 42 (1), 5-8. https://doi.org/10,1248 / cpb.42.5
  • Jennings AT (1999) Lyophilization, Introductionand Basic Principles. CRC Press, USA.
  • Kasper JC, Friess W (2011) The freezing step in lyophili¬zation: Physico-chemical fundamentals, freezing methods and consequences on process performance and quality at-tributes of biopharmaceuticals. Eur J Pharm Biopharm 78, 248-263. https://doi.org/10.1016/j.ejpb.2011.03.010
  • Kuo JC, Ockerman HW (1984) International Association of Milk, Food, and Environmental Sanitarians Effects of Rigor, Salt, Freezing, Lyophilization and Storage Time on pH, Water-Holding Capacity and Soluble Protein Nitrogen in Beef Muscle. Journal of Food Protection 47 (4) 317-321. https://jfoodprotection.org/doi/abs/10.4315/0362-028X-47.4.316
  • Lu X, Pikal MJ (2004) Freeze-Drying of Mannitol–Trehalose–Sodium Chloride-Based Formulations: The Impact of Annealing on Dry Layer Resistance to Mass
  • Lueckel B, Bodmer D, Helk B, Leuenberger H (1998) Formulations of sugars with amino acids or mannitol – influence of concentration ratio on properties of the freeze-concentrate and the lyophilisate. Pharm Dev Technol, 3, 325–336. https://doi.org/10.3109/10837459809009860
  • Martin C, Ross C, Peacock T, Ward K R (2007) Application of Electrical Impedance Analysis for Investigation of Nutraceutical Formulation Stability in the Frozen State. SET for Britain presented at the House of Commons, London,
  • Meister E, Gieseler H (2009) Freeze-Dry Microscopy of Protein/Sugar Mixtures: Drying Behavior, Interpretation of Collapse Temperatures and a Comparison to Corresponding Glass Transition Data. J PharmSci, 98(9), 3072-3087. https://doi.org/10.1002/jps.21586
  • Meister E, Šaši S, Gieseler H (2009) Freeze-dry microscopy: impact of nucleation temperature and excipient concentration on collapse temperature data. AAPS Pharm Sci Tech 10 (2), 582–588. https://doi.org/10.1208/s12249-009-9245-y
  • Patel RM, Hurwitz A (1972) Eutectic Temperature Determination of Preformulation Systems and Evaluation by Controlled Freeze Drying. J Pharm Sci 61 (11), 1806-1810. https://doi.org/10.1002/jps.2600611125
  • Pikal MJ (1990) The collapse temperature in freeze drying: Dependence on measurement methology and rate of water removal from the glassy phase. Inter J Pharm, 62, 165-186. https://doi.org/10.1016/0378-5173(90)90231-R
  • Pikal MJ (2001) Lyophilization. In Encyclopedia of Pharmaceutical Technology; Swarbrick, J, Boylan, J.C., Eds.; Marcel Dekker, New York, USA.
  • Pyne A, Surana R, Suryanararyanan R (2002) Crystallization of mannitol below Tg’ during freeze-drying in binary and ternary aqueous systems, Pharm Res, 19, 901–908. https://doi.org/10.1023/a:1016129521485
  • Rey L (1960) Thermal analysis of eutectics in freezing solutions. Ann NY Acad Sci 85(2), 510–34. https://doi.org/10.1111/j.1749-6632.1960.tb49979.x
  • Rey L, May JC (2010) Freese Drying/ Lyophilization of Pharmaceutical and Biological Products, Informa Healthcare, London, UK.
  • Shah, B, Kakumanu VK, Bansal AK (2006). Analytical techniques for quantification of amorphous/crystalline phases in pharmaceutical solids. J Pharm Sci 95, 1641-1665. https://doi.org/10.1002/jps.20644
  • Shalaev EY, Franks F (1996) Crystalline and amorphous phases in the ternary system water–sucrose–sodium chloride. J Phys Chem, 100, 1144–1152. https://doi.org/10.1021/jp951052r
  • Telang C, Yu L, Suryanarayanan R (2003) Effective Inhibition of Mannitol Crystallization in Frozen Solutions by Sodium Chloride. Pharm Res 20 (4), 660-667. https://doi.org/10,1023 / a: 1023263203188
  • Van den Berg L, Rose D (1959) Effect of freezing on the pH and composition of sodium and potassium phosphate solutions: the reciprocal system KH2PO4-Na2HPO4-H2O. Arch Biochem Biophys, 81 (2), 319–29. https://doi.org/10.1016/0003-9861(59)90209-7
  • Yu L, Milton N, Groleau E, Mishra D, Vansickle R (1999) Existence of a mannitol hydrate during freeze-drying and practical implications. J Pharm Sci 88, 196–198. https://doi.org/10.1021/js980323h
  • Zhai S, Taylor R, Sanches R, Slater NKH (2003) Measurement of lyophilisation primary drying rates by freeze drying microscopy. Chem Eng Sci 58 (11), 2313-2323. https://doi.org/10.1016/S0009-2509(03)00090-3andr

Demir, Potasyum, Magnezyum ve Sodyum Tuzlarını İçeren Mannitol Çözeltilerinin Liyofilizasyon Esnasında Kritik Formülasyon Sıcaklıklarının Differensiyel Termal Analiz (DTA) Cihazı ve Freeze Dry Mikroskop (FDM) ile Belirlenmesi

Year 2020, Volume: 2 Issue: 2, 39 - 44, 30.12.2020

Gülseren Yıldız Öz

Abstract

Bir maddenin kinetik saatinin yavaşlatıldığı liyofilizasyon prosesi, her madde veya çözelti için özel olmaktadır. Her maddenin kendisine özel bazı önemli hal değişim sıcaklıları bulunmaktadır. Ötektik nokta (Teu), camsı geçiş sıcaklığı (Tg) ve çökme sıcaklığının (Tc) belirlenmesi maddenin tanımlanabilmesi ve kaliteli kuruma için proses hazırlanmasında gerekli olmaktadır. Bu sıcaklıkların belirlenebilmesi için termal analiz yöntemleri ve dondurulmuş üründeki değişimlerin mikroskobik olarak incelendiği freeze dry mikroskop kullanılmaktadır. D-Mannitol, proses geliştirmenin farklı gereksinimlerini karşılamak üzere tasarlanabilen çok yönlü kryoprezeravatif bir madde olması nedeniyle liyofilizasyonda yaygın olarak kullanılmaktadır. Tuzlar oluşturdukları kristal kafesler ile suyun uzaklaştırılmasını kolaylaştırarak mükemmel bir kuruma sağladıklarından liyofilizasyonda tercih edilmektedir. Bu çalışmada mannitol çözeltisine eklenen farklı mineral tuzların varlığında çözeltinin kritik sıcaklık değerleri belirlenmeye çalışılmıştır. Bu amaçla Differansiyel Termal Analiz (DTA) cihazı ve Freeze Dry Mikroskop (FDM) kullanılmıştır. Demir, potasyum, magnezyum ve sodyum tuzlarını içeren mannitol çözeltilerinin liyofilizasyon esnasında kritik formülasyon sıcaklıkları belirlenmiştir. Mannitolün Teu ve Tc değerleri yüksek olduğu için bu değerler liyofilizasyonu kalitesi açısından başarılı bir sonucu ifade etmektedir. Tuzlar Teu ve Tc değerlerini düşürerek primer kurutmanın daha düşük sıcaklıklarda bitirilmesini gerektirmektedir. Bu sonuç zor ve daha masraflı bir primer kurutma prosesini ifade etmektedir. Tüm bunlara rağmen tuzların daha stabil ve kaliteli kuruma sağladıkları ve mannitolün yapısını güçlendirdikleri bilinmektedir. Bu çalışmada farklı tuzları içeren mannitol çözeltileri dondurularak kritik formülasyon sıcaklıkları belirlenmeye çalışılmıştır.

Keywords

Liyofilizasyon Mannitol Mineral Tuzları

References

  • Adams GDJ, Cook I, Ward KR (2015) The Principles of Freeze-Drying. Methods Mol Biol 1257:121-143. https://doi.org/10.1007/978-1-4939-2193-5_4
  • Andrade ÂL, Militani IA, de Almeida KJ, Belchior JC, dos Reis SC, Costa e Silva RMF, Domingues RZ (2018) Theoretical and Experimental Studies of the Controlled Release of Tetracycline Incorporated into Bioactive Glasses. AAPS PharmSciTech 19 (3), 1287-1296. https://doi.org/10.1208/s12249-017-0931-x
  • Arshad M S, Smith G, Polygalov E, Ermolina I (2014). Through-vial impedance spectroscopy of critical events during the freezing stage of the lyophilization cycle: the example of the impact of sucrose on the crystallization of mannitol. Eur. J Pharm Biopharm 87, 598–605. https://doi.org/10.1016/j.ejpb.2014.05.005
  • Cavatur RK, Vemuri NM, Pyne A, Chrzan Z, Toledo-Velasquez D, Suryanarayanan R (2002) Crystallization behavior of mannitol in frozen aqueous solutions. Pharm Res, 19 (6), 894–900. https://doi.org/10.1023/a:1016177404647
  • Chang BS, Randall CS (1992). Use of subambient thermal analysis to optimize protein lyophilization. Cryobiology, 29 (5), 632–56. https://doi.org/10.1016/0011-2240(92)90067-C
  • Day JG, Stacey GN (2007) Cryopreservation and Freeze- Drying Protocols, Human Press, New Jersey.
  • Hawe A, Frieß W (2006) Impact of freezing procedure and annealing on the physico-chemical properties and the formation of mannitol hydrate in mannitol-sucrose-NaCl formulations. Eur J Pharm Biopharm 64, 316–325. https://doi.org/10.1016/j.ejpb.2006.06.002
  • Horn J, Friess W (2018) Detection of Collapse and Crystallization of Saccharide, Protein, and Mannitol Formulations by Optical Fibers in Lyophilization. Frontiers in Chemistry 6 (4) 1-9 https://doi.org/10.3389/fchem.2018.00004
  • Ito K (1971) Freeze drying of pharmaceuticals. Eutectic temperature and collapse temperature of solute matrix upon freeze drying of three component systems. Chem Pharm Bull 19 (6), 1095–102. https://doi.org/10.1248/cpb.19.1095
  • Izutsu K, Kojima S(2002) Excipient crystallinity and its protein-structurestabilizing effect during freeze-drying. J Pharm Pharmacol. 54, 1033–1039. https://doi.org/10.1211/002235702320266172
  • Izutsu K, Yoshioka S, Terao T (1994) Effect of mannitol crystallinity on the stabilization of enzymes during freeze-drying. Chem Pharm Bull (Tokyo) 42 (1), 5-8. https://doi.org/10,1248 / cpb.42.5
  • Jennings AT (1999) Lyophilization, Introductionand Basic Principles. CRC Press, USA.
  • Kasper JC, Friess W (2011) The freezing step in lyophili¬zation: Physico-chemical fundamentals, freezing methods and consequences on process performance and quality at-tributes of biopharmaceuticals. Eur J Pharm Biopharm 78, 248-263. https://doi.org/10.1016/j.ejpb.2011.03.010
  • Kuo JC, Ockerman HW (1984) International Association of Milk, Food, and Environmental Sanitarians Effects of Rigor, Salt, Freezing, Lyophilization and Storage Time on pH, Water-Holding Capacity and Soluble Protein Nitrogen in Beef Muscle. Journal of Food Protection 47 (4) 317-321. https://jfoodprotection.org/doi/abs/10.4315/0362-028X-47.4.316
  • Lu X, Pikal MJ (2004) Freeze-Drying of Mannitol–Trehalose–Sodium Chloride-Based Formulations: The Impact of Annealing on Dry Layer Resistance to Mass
  • Lueckel B, Bodmer D, Helk B, Leuenberger H (1998) Formulations of sugars with amino acids or mannitol – influence of concentration ratio on properties of the freeze-concentrate and the lyophilisate. Pharm Dev Technol, 3, 325–336. https://doi.org/10.3109/10837459809009860
  • Martin C, Ross C, Peacock T, Ward K R (2007) Application of Electrical Impedance Analysis for Investigation of Nutraceutical Formulation Stability in the Frozen State. SET for Britain presented at the House of Commons, London,
  • Meister E, Gieseler H (2009) Freeze-Dry Microscopy of Protein/Sugar Mixtures: Drying Behavior, Interpretation of Collapse Temperatures and a Comparison to Corresponding Glass Transition Data. J PharmSci, 98(9), 3072-3087. https://doi.org/10.1002/jps.21586
  • Meister E, Šaši S, Gieseler H (2009) Freeze-dry microscopy: impact of nucleation temperature and excipient concentration on collapse temperature data. AAPS Pharm Sci Tech 10 (2), 582–588. https://doi.org/10.1208/s12249-009-9245-y
  • Patel RM, Hurwitz A (1972) Eutectic Temperature Determination of Preformulation Systems and Evaluation by Controlled Freeze Drying. J Pharm Sci 61 (11), 1806-1810. https://doi.org/10.1002/jps.2600611125
  • Pikal MJ (1990) The collapse temperature in freeze drying: Dependence on measurement methology and rate of water removal from the glassy phase. Inter J Pharm, 62, 165-186. https://doi.org/10.1016/0378-5173(90)90231-R
  • Pikal MJ (2001) Lyophilization. In Encyclopedia of Pharmaceutical Technology; Swarbrick, J, Boylan, J.C., Eds.; Marcel Dekker, New York, USA.
  • Pyne A, Surana R, Suryanararyanan R (2002) Crystallization of mannitol below Tg’ during freeze-drying in binary and ternary aqueous systems, Pharm Res, 19, 901–908. https://doi.org/10.1023/a:1016129521485
  • Rey L (1960) Thermal analysis of eutectics in freezing solutions. Ann NY Acad Sci 85(2), 510–34. https://doi.org/10.1111/j.1749-6632.1960.tb49979.x
  • Rey L, May JC (2010) Freese Drying/ Lyophilization of Pharmaceutical and Biological Products, Informa Healthcare, London, UK.
  • Shah, B, Kakumanu VK, Bansal AK (2006). Analytical techniques for quantification of amorphous/crystalline phases in pharmaceutical solids. J Pharm Sci 95, 1641-1665. https://doi.org/10.1002/jps.20644
  • Shalaev EY, Franks F (1996) Crystalline and amorphous phases in the ternary system water–sucrose–sodium chloride. J Phys Chem, 100, 1144–1152. https://doi.org/10.1021/jp951052r
  • Telang C, Yu L, Suryanarayanan R (2003) Effective Inhibition of Mannitol Crystallization in Frozen Solutions by Sodium Chloride. Pharm Res 20 (4), 660-667. https://doi.org/10,1023 / a: 1023263203188
  • Van den Berg L, Rose D (1959) Effect of freezing on the pH and composition of sodium and potassium phosphate solutions: the reciprocal system KH2PO4-Na2HPO4-H2O. Arch Biochem Biophys, 81 (2), 319–29. https://doi.org/10.1016/0003-9861(59)90209-7
  • Yu L, Milton N, Groleau E, Mishra D, Vansickle R (1999) Existence of a mannitol hydrate during freeze-drying and practical implications. J Pharm Sci 88, 196–198. https://doi.org/10.1021/js980323h
  • Zhai S, Taylor R, Sanches R, Slater NKH (2003) Measurement of lyophilisation primary drying rates by freeze drying microscopy. Chem Eng Sci 58 (11), 2313-2323. https://doi.org/10.1016/S0009-2509(03)00090-3andr
There are 31 citations in total.

Details

Primary Language Turkish
Subjects Veterinary Surgery
Journal Section Research Article
Authors

Gülseren Yıldız Öz 0000-0003-1201-4920

Publication Date December 30, 2020
Published in Issue Year 2020Volume: 2 Issue: 2

Cite

APA Yıldız Öz, G. (2020). Demir, Potasyum, Magnezyum ve Sodyum Tuzlarını İçeren Mannitol Çözeltilerinin Liyofilizasyon Esnasında Kritik Formülasyon Sıcaklıklarının Differensiyel Termal Analiz (DTA) Cihazı ve Freeze Dry Mikroskop (FDM) ile Belirlenmesi. Turkish Veterinary Journal, 2(2), 39-44.
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